RENAL MASS AND LOCALIZED RENAL CANCER: EVALUATION

Purpose

This AUA Guidelines focuses on the evaluation and management of clinically

localized sporadic renal masses suspicious for renal cell carcinoma (RCC) in adults,

including solid enhancing renal tumors and Bosniak 3 and 4 complex cystic renal

masses. Some patients with clinically localized renal masses may present with

findings suggesting aggressive tumor biology or may be upstaged on exploration

or final pathology. Management considerations pertinent to the urologist in such

patients will also be discussed. The follow-up of renal cancer patients after

intervention is also addressed, including recommendations for periodic clinical

follow-up and abdominal and chest imaging. Practice patterns regarding such

tumors vary considerably, and the literature regarding evaluation, management,

and surveillance has been rapidly evolving. Notable examples include

controversies about the role of renal mass biopsy (RMB) and concerns regarding

overutilization of radical nephrectomy (RN). Please also refer to the associated

Renal Mass and Localized Renal Cancer Treatment and Follow-up after

Intervention algorithms.

Methodology

The systematic review utilized in the creation of this guideline was completed in

part through the Agency for Healthcare Research and Quality (AHRQ) and through

additional supplementation that further addressed additional key questions and

more recently published literature. A research librarian experienced in conducting

literature searches for comparative effectiveness reviews searched in MEDLINE®,

Embase®, the Cochrane Library, the Database of Abstracts of Reviews of Effects,

the Health Technology Assessment Database, and the UK National Health Service

Economic Evaluation database to capture both published and gray literature

published from January 1, 1997 through May 1, 2015. A supplemental search was

conducted adding additional literature published through August 2015, and a final

update search was conducted through July 2016.

A systematic review was conducted in 2013 to identify published articles relevant

to key questions specified by the Panel related to kidney neoplasms and their

follow-up (imaging, renal function, markers, biopsy, and prognosis). This search

covered English-language articles published between January 1999 and 2011. An

updated query was later conducted to include studies published through August

2012.

In January of 2021, the Renal Mass and Localized Renal Cancer guideline

underwent an additional amendment based on a current literature search. This

Approved by the AUA

Board of Directors April

2021

Authors’ disclosure of po-

tential conflicts of interest

and author/staff contribu-

tions appear at the end of

the article.

Urological Association

American Urological Association (AUA)

RENAL MASS AND LOCALIZED RENAL CANCER:

EVALUATION, MANAGEMENT, AND FOLLOW-UP: AUA

GUIDELINE

Steven Campbell, MD, PhD; Robert G. Uzzo, MD; Mohamad E. Allaf, MD; Jay Todd

Bishoff, MD; Eric B. Bass, MD, MPH; Jeffrey A. Cadeddu, MD; Anthony Chang,

MD; Sam S. Chang, MD; Peter E. Clark, MD; Jonathan A. Coleman, MD; Philipp

Dahm, MD; Brian J. Davis, MD, PhD; Ithaar H. Derweesh, MD; Mireya Diaz, PhD;

Sherri M. Donat , MD; Leo Giambarresi, PhD; Debra A. Gervais, MD; S. Duke

Herrell III, MD; Susan Hilton, MD; Susie L. Hu, MD; Eric Jonasch, MD; Jose A.

Karam, MD; Brian R. Lane, MD, PhD; Bradley C. Leibovich, MD, FACS; Daniel Wei

Lin, MD; Philip M. Pierorazio, MD; Victor Edward Reuter, MD; Lesley Souter, PhD

Panel Nomination

Acknowledgment:

The AUA would like to

acknowledge the following

organizations: College of

American Pathologists

(CAP); Society of Urologic

Oncologists (SUO); Ameri-

can College of Radiology

(ACR); American Society of

Nephrology (ASN); En-

dourological Society; and

the Society of Interventional

Radiology for participation

in the development of this

guideline.

American Urological Association (AUA)

literature search retrieved additional studies published between July 2016 to October 2020 using the same Key

Questions and search criteria from the Renal Mass and Localized Renal Cancer guideline. Nineteen studies were

identified from this search to provide data relevant to the management and treatment of Renal Mass. In addition, the

Follow-Up for Clinically Localized Renal Neoplasms guideline published in 2013 was merged with the Renal Mass and

Localized Renal Cancer guideline. Although the systematic search for follow-up interventions was not updated to

2020, the panel members conducted a comprehensive review of all evidence published since the original guideline.

The language of many statements has been refined for clarity. For all evidence-based statements, supporting

studies were identified only in the original systematic review and the evidence strength was not altered.

When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A

(high), B (moderate) or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of

sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions.

GUIDELINE STATEMENTS

INITIAL EVALUATION AND DIAGNOSIS

Evaluation

1. In patients with a solid or complex cystic renal mass, clinicians should obtain high quality, multiphase, cross-

sectional abdominal imaging to optimally characterize and clinically stage the renal mass. Characterization of the

renal mass should include assessment of tumor complexity, degree of contrast enhancement (where applicable), and

presence or absence of fat. (Clinical Principle)

2. In patients with suspected renal malignancy, clinicians should obtain a comprehensive metabolic panel, complete

blood count, and urinalysis. Metastatic evaluation should include chest imaging to evaluate for possible thoracic

metastases. (Clinical Principle)

3. For patients with a solid or Bosniak 3/4 complex cystic renal mass, clinicians should assign chronic kidney disease

(CKD) stage based on glomerular filtration rate (GFR) and degree of proteinuria. (Expert Opinion)

Counseling

4. In patients with a solid or Bosniak 3/4 complex cystic renal mass, a urologist should lead the counseling process

and should consider all management strategies. A multidisciplinary team should be included when necessary. (Expert

Opinion)

5. Clinicians should provide counseling that includes current perspectives about tumor biology and a patient-specific

risk assessment inclusive of sex, tumor size/complexity, histology (when obtained), and imaging characteristics. For

cT1a tumors, the low oncologic risk of many small renal masses should be reviewed. (Clinical Principle)

6. During counseling of patients with a solid or Bosniak 3/4 complex cystic renal mass, clinicians must review the

most common and serious urologic and non-urologic morbidities of each treatment pathway and the importance of

patient age, comorbidities/frailty, and life expectancy. (Clinical Principle)

7. Clinicians should review the importance of renal functional recovery related to renal mass management, including

the risks of progressive CKD, potential short- or long-term need for renal replacement therapy, and long-term overall

survival considerations. (Clinical Principle)

8. Clinicians should consider referral to nephrology in patients with a high risk of CKD progression, including those

with estimated glomerular filtration rate (eGFR) less than 45 mL/min/1.73m2, confirmed proteinuria, diabetics with

preexisting CKD, or whenever eGFR is expected to be less than 30 mL/min/1.73m2 after intervention. (Expert

Opinion)

9. Clinicians should recommend genetic counseling for any of the following: all patients ≤ 46 years of age with renal

malignancy, those with multifocal or bilateral renal masses, or whenever 1) the personal or family history suggests a

familial renal neoplastic syndrome; 2) there is a first-or second-degree relative with a history of renal malignancy or

Renal Mass and

Localized Renal Cancer

a known clinical or genetic diagnosis of a familial renal neoplastic syndrome (even if kidney cancer has not been

observed); or 3) the patient’s pathology demonstrates histologic findings suggestive of such a syndrome. (Expert

Opinion)

Renal Mass Biopsy (RMB)

10. When considering the utility of RMB, patients should be counseled regarding rationale, positive and negative

predictive values, potential risks and non-diagnostic rates of RMB. (Moderate Recommendation; Evidence Level:

Grade C)

11. Clinicians should consider RMB when a mass is suspected to be hematologic, metastatic, inflammatory, or

infectious. (Clinical Principle)

12. In the setting of a solid renal mass, RMB should be obtained on a utility-based approach whenever it may

influence management. RMB is not required for 1) young or healthy patients who are unwilling to accept the

uncertainties associated with RMB; or 2) older or frail patients who will be managed conservatively independent of

RMB findings. (Expert Opinion)

13. For patients with a solid renal mass who elect RMB, multiple core biopsies should be performed and are preferred

over fine needle aspiration (FNA). (Moderate Recommendation; Evidence Level: Grade C)

MANAGEMENT

Partial Nephrectomy (PN) and Nephron-Sparing Approaches

14. Clinicians should prioritize PN for the management of the cT1a renal mass when intervention is indicated. In this

setting, PN minimizes the risk of CKD or CKD progression and is associated with favorable oncologic outcomes,

including excellent local control. (Moderate Recommendation; Evidence Level: Grade B)

15. Clinicians should prioritize nephron-sparing approaches for patients with solid or Bosniak 3/4 complex cystic

renal masses and an anatomic or functionally solitary kidney, bilateral tumors, known familial RCC, preexisting CKD,

or proteinuria. (Moderate Recommendation; Evidence Level: Grade C)

16. Nephron-sparing approaches should be considered for patients with solid or Bosniak 3/4 complex cystic renal

masses who are young, have multifocal masses, or comorbidities that are likely to impact renal function in the

future, including but not limited to moderate to severe hypertension, diabetes mellitus, recurrent urolithiasis, or

morbid obesity. (Moderate Recommendation; Evidence Level: Grade C)

17. In patients who elect PN, clinicians should prioritize preservation of renal function by optimizing nephron mass

preservation and avoiding prolonged warm ischemia. (Expert Opinion)

18. For patients undergoing PN, clinicians should prioritize negative surgical margins. The extent of normal

parenchyma removed should be determined by surgeon discretion taking into account the clinical situation and

tumor characteristics, including growth pattern, and interface with normal tissue. Tumor enucleation should be

considered in patients with familial RCC, multifocal disease, or severe CKD to optimize parenchymal mass

preservation. (Expert Opinion)

Radical Nephrectomy (RN)

19. Clinicians should consider RN for patients with a solid or Bosniak 3/4 complex cystic renal mass whenever

increased oncologic potential is suggested by tumor size, RMB (if obtained), and/or imaging. (Moderate

Recommendation; Evidence Level: Grade B) In this setting, RN is preferred if all of the following criteria are met: 1)

high tumor complexity and PN would be challenging even in experienced hands; 2) no preexisting CKD or

proteinuria; and 3) normal contralateral kidney and new baseline eGFR will likely be greater than 45 mL/min/1.73m2

even if RN is performed. If all of these criteria are not met, PN should be considered unless there are overriding

concerns about the safety or oncologic efficacy of PN. (Expert Opinion)

Surgical Principles

20. For patients who are undergoing surgical excision of a renal mass with clinically concerning regional

lymphadenopathy, clinicians should perform a lymph node dissection including all clinically positive nodes for staging

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

purposes. (Expert Opinion)

21. For patients who are undergoing surgical excision of a renal mass, clinicians should perform adrenalectomy if

imaging and/or intraoperative findings suggest metastasis or direct invasion of the adrenal gland. (Clinical Principle)

22. In patients undergoing surgical excision of a renal mass, a minimally invasive approach should be considered

when it would not compromise oncologic, functional, and perioperative outcomes. (Expert Opinion)

Other Considerations

23. Pathologic evaluation of the adjacent renal parenchyma should be performed and recorded after PN or RN to

assess for possible intrinsic renal disease, particularly for patients with CKD or risk factors for developing CKD.

(Clinical Principle)

24. Clinicians should consider referral to medical oncology whenever there is concern for potential clinical metastasis

or incompletely resected disease (macroscopic positive margin or gross residual disease). Patients with high-risk or

locally advanced, fully resected renal cancers should be counselled about the risks/benefits of adjuvant therapy and

encouraged to participate in adjuvant clinical trials, facilitated by medical oncology consultation when needed.

(Clinical Principle)

Thermal Ablation (TA)

25. Clinicians should consider TA as an alternate approach for the management of cT1a solid renal masses <3 cm in

size. For patients who elect TA, a percutaneous technique is preferred over a surgical approach whenever feasible to

minimize morbidity. (Moderate Recommendation; Evidence Level: Grade C)

26. Both radiofrequency ablation (RFA) and cryoablation may be offered as options for patients who elect TA.

(Conditional Recommendation; Evidence Level: Grade C)

27. A RMB should be performed prior to (preferred) or at the time of ablation to provide pathologic diagnosis and

guide subsequent surveillance. (Expert Opinion)

28. Counseling about TA should include information regarding an increased likelihood of tumor persistence or local

recurrence after primary TA relative to surgical excision, which may be addressed with repeat ablation if further

intervention is elected. (Strong Recommendation; Evidence Level: Grade B)

Active Surveillance (AS)

29. For patients with a solid renal mass < 2cm, or those that are complex but predominantly cystic, clinicians may

elect AS with potential for delayed intervention for initial management. (Conditional Recommendation; Evidence

Level: Grade C)

30. For patients with a solid or Bosniak 3/4 complex cystic renal mass, clinicians should prioritize AS/expectant

management when the anticipated risk of intervention or competing risks of death outweigh the potential oncologic

benefits of active treatment. In asymptomatic patients, the panel recommends periodic clinical surveillance and/or

imaging based on shared decision making. (Clinical Principle)

31. For patients with a solid or Bosniak 3/4 complex cystic renal mass in whom the risk/benefit analysis for

treatment is equivocal and who prefer AS, clinicians should consider RMB (if the mass is solid or has solid

components) for further oncologic risk stratification. Repeat cross-sectional imaging should be obtained

approximately 3-6 months later to assess for interval growth. Periodic clinical/imaging surveillance can then be

based on growth rate and shared decision-making with intervention recommended if substantial interval growth is

observed or if other clinical/imaging findings suggest that the risk/benefit analysis is no longer equivocal or favorable

for continued AS. (Expert Opinion)

32. For patients with a solid or Bosniak 3/4 complex cystic renal mass in whom the anticipated oncologic benefits of

intervention outweigh the risks of treatment and competing risks of death, clinicians should recommend intervention.

AS with potential for delayed intervention may be pursued only if the patient understands and is willing to accept the

associated oncologic risks. In this setting, clinicians should encourage RMB (if the mass is predominantly solid) for

additional risk stratification. If the patient continues to prefer AS, close clinical and cross-sectional imaging

surveillance with periodic reassessment and counseling should be recommended. (Moderate Recommendation;

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

Evidence Level: Grade C)

FOLLOW-UP AFTER INTERVENTION

General Principles

33. Clinicians coordinating follow-up for patients who have undergone intervention for a renal mass should discuss

the implications of stage, grade, and histology including the risks of recurrence and possible sequelae of treatment.

Patients with pathologically-proven benign renal masses should undergo occasional clinical evaluation and laboratory

testing for sequelae of treatment but most do not require routine periodic imaging. (Expert Opinion)

34. Patients with treated malignant renal masses should undergo periodic medical history, physical examination,

laboratory studies, and imaging directed at detecting signs and symptoms of metastatic spread and/or local

recurrence as well as evaluation for possible sequelae of treatment. (Clinical Principle)

35. Patients with treated malignant renal masses should have periodic laboratory testing including serum creatinine,

eGFR, and urinalysis. Other laboratory evaluations (e.g., complete blood count, lactate dehydrogenase, liver function

tests, alkaline phosphatase and calcium level) may be obtained at the discretion of the clinician or if advanced

disease is suspected. (Expert Opinion)

36. Patients undergoing follow-up for treated renal masses with progressive renal insufficiency or proteinuria should

be referred to nephrology. (Expert Opinion)

37. Patients undergoing follow-up for treated malignant renal masses should only undergo bone scan if one or more

of the following is present: clinical symptoms such as bone pain, elevated alkaline phosphatase, or radiographic

findings suggestive of a bony neoplasm. (Moderate Recommendation; Evidence Level: Grade C)

38. Patients undergoing follow-up for treated malignant renal masses with acute neurological signs or symptoms

should undergo prompt magnetic resonance imaging (MRI) or computed tomography (CT) scanning of the brain and/

or spine. (Strong Recommendation; Evidence Level: Grade A)

39. For patients undergoing follow-up for treated malignant renal masses, additional site-specific imaging can be

ordered as warranted by clinical symptoms suggestive of recurrence or metastatic spread. Positron emission

tomography (PET) scan should not be obtained routinely but may be considered selectively. (Moderate

Recommendation; Evidence Level: Grade C)

40. Patients with findings suggestive of metastatic renal malignancy should be evaluated to define the extent of

disease and referred to medical oncology. Surgical resection or ablative therapies should be considered in select

patients with isolated or oligo-metastatic disease. (Expert Opinion)

41. Patients with findings suggesting a new renal primary or local recurrence of renal malignancy should undergo

metastatic evaluation including chest and abdominal imaging. If the new primary or recurrence is isolated to the

ipsilateral kidney and/or retroperitoneum, a urologist should be involved in the decision-making process, and surgical

resection or ablative therapies may be considered. (Expert Opinion)

Follow-up After Surgery

42. Clinicians should classify patients who have been managed with surgery (PN or RN) for a malignant renal mass

into one of the following risk groups for follow-up:

If final microscopic surgical margins are positive for cancer, the risk category should be considered at least one level

higher, and increased clinical vigilance should be exercised. (Expert Opinion)

Low Risk (LR): pT1 and Grade 1/2

Intermediate Risk (IR): pT1 and Grade 3/4, or pT2 any Grade

High Risk (HR): pT3 any Grade

Very High Risk (VHR): pT4 or pN1, or sarcomatoid/rhabdoid dedifferentia-

tion, or macroscopic positive margin

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43. Patients managed with surgery (PN or RN) for a renal malignancy should undergo abdominal imaging according

to Table 1, with CT or MRI pre- and post-intravenous contrast preferred. (Moderate Recommendation; Evidence

Strength: Grade C). After 2 years, abdominal ultrasound (US) alternating with cross-sectional imaging may be

considered in the LR and IR groups at physician discretion. After 5 years, informed/shared decision-making should

dictate further abdominal imaging. (Expert Opinion)

44. Patients managed with surgery (PN or RN) for a renal malignancy should undergo chest imaging (chest x-ray

[CXR] for LR and IR; CT chest preferred for HR and VHR) according to Table 1. (Moderate Recommendation;

Evidence Strength: Grade C). After 5 years, informed/shared decision-making discussion should dictate further chest

imaging and CXR may be utilized instead of chest CT for HR and VHR (Expert Opinion)

Table 1: Recommended follow-up schedule after surgery for renal cancer (in months)*

*Follow-up timeline is approximate and allows flexibility to accommodate reasonable patient, caregiver, and

institutional needs. Each follow-up visit should include relevant history, physical examination, laboratory testing, and

abdominal and chest imaging. Overall, 30% of renal cancer recurrences after surgery are diagnosed beyond 60

months.

Informed/shared decision-making should guide surveillance decisions beyond 60 months.

Follow-up After TA

45. Patients undergoing ablative procedures with biopsy that confirmed malignancy or was non-diagnostic should

undergo pre- and post-contrast cross-sectional abdominal imaging within 6 months (if not contraindicated).

Subsequent follow-up should be according to the recommendations for the IR postoperative protocol (Table 1).

(Expert Opinion)

Risk 3 6 9 12 18 24 30 36 48 60 72-84 96-120

LR x x x x x x

IR x x x x x x x x

HR x x x x x x x x x x

VHR x x x x x x x x x x x x

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

INTRODUCTION

PURPOSE

This AUA Guidelines focuses on the evaluation and

management of clinically localized sporadic renal

masses suspicious for RCC in adults, including solid

enhancing renal tumors and Bosniak 3 and 4 complex

cystic renal masses. Some patients with clinically

localized renal masses may present with findings

suggesting aggressive tumor biology or may be

upstaged on exploration or final pathology.

Management considerations pertinent to the urologist in

such patients will also be discussed. The follow-up of

renal cancer patients after intervention is also

addressed including recommendations for periodic

clinical follow-up and abdominal and chest imaging.

Practice patterns regarding such tumors vary

considerably and the literature regarding evaluation,

management, and surveillance has been rapidly

evolving. Notable examples include controversies about

the role of RMB and concerns about overutilization of

RN.

METHODOLOGY

Systematic Review of Renal Mass.

The systematic review utilized in the creation of this

guideline was completed in part through the AHRQ and

through additional supplementation that further

addressed additional key questions and more recently

published literature. A research librarian experienced in

conducting literature searches for comparative

effectiveness reviews searched in MEDLINE®, Embase

®, the Cochrane Library, the Database of Abstracts of

Reviews of Effects, the Health Technology Assessment

Database, and the UK National Health Service Economic

Evaluation database to capture both published and gray

literature published from January 1, 1997 through May

1, 2015. A supplemental search was conducted adding

additional literature published through August 2015,

and a final update search was conducted through July

2016.

Systematic Review Follow-up Renal Cancer.

A systematic review was conducted to identify

published articles relevant to key questions specified by

the Panel related to kidney neoplasms and their follow-

up (imaging, renal function, markers, biopsy, and

prognosis). This search covered articles in English

published between January 1999 and 2011. An updated

query was later conducted to include studies published

through August 2012. Study designs consisting of

clinical trials (randomized or not), observational studies

(cohort, case-control, case series) and systematic

reviews were included. All other study types were

excluded. Studies with full-text publication available

were included, but studies in abstract form only were

excluded.

Combination of Guidelines

In January of 2021, the Renal Mass and Localized Renal

Cancer guideline underwent an additional amendment

based on current literature. The updated literature

search retrieved additional studies published between

July 2016 to October 2020 using the same search

strategy from the Renal Mass and Localized Renal

Cancer guideline. Following study selection using the

original PICO criteria, as reporting data relevant to the

management and treatment of Renal Mass. In addition,

the Follow-Up for Clinically Localized Renal Neoplasms

guideline published in 2013 was merged with the Renal

Mass and Localized Renal Cancer guideline. Although

the systematic search for follow-up interventions was

not updated to 2020, the panel members conducted a

comprehensive review of all evidence published since

the original guideline. The language of many

statements has been refined for clarity. For all

evidence-based statements, supporting studies were

identified only in the original systematic review and the

evidence strength was not altered.

Assessment of Risk-of-Bias of Individual Studies.

Citations identified by the systematic search were

screened independently by two reviewers using

predefined PICO criteria. One reviewer completed data

abstraction and a second reviewer checked abstraction

for accuracy. Two reviewers independently assessed

risk of bias for individual studies. The Cochrane

Collaboration’s tool was used for assessing the risk of

bias of randomized controlled trials (RCTs).

For

nonrandomized studies of treatment interventions, the

reviewers used the Risk of Bias in Non-Randomized

Studies – of Intervention (ROBINS-I). For diagnostic

studies, we used the quality assessment tool for

diagnostic accuracy studies (QUADAS -2).

3,4

Differences

between reviewers were resolved through consensus.

Determination of Evidence Strength.

The categorization of evidence strength is conceptually

distinct from the quality of individual studies. Evidence

strength refers to the body of evidence available for a

particular question and includes not only individual

study quality but consideration of study design,

consistency of findings across studies, adequacy of

sample sizes, and generalizability of samples, settings,

and treatments for the purposes of the guideline. The

AUA categorizes body of evidence strength as Grade A

(well-conducted and highly-generalizable RCTs or

exceptionally strong observational studies with

consistent findings), Grade B (RCTs with some

weaknesses of procedure or generalizability or

moderately strong observational studies with consistent

findings), or Grade C (RCTs with serious deficiencies of

procedure or generalizability or extremely small sample

sizes or observational studies that are inconsistent,

have small sample sizes, or have other problems that

potentially confound interpretation of data). By

definition, Grade A evidence is evidence about which

the Panel has a high level of certainty, Grade B

evidence is evidence about which the Panel has a

moderate level of certainty, and Grade C evidence is

evidence about which the Panel has a low level of

certainty.

AUA Nomenclature: Linking Statement Type to

Evidence Strength.

The AUA nomenclature system explicitly links statement

type to body of evidence strength, level of certainty,

magnitude of benefit or risk/burdens, and the Panel’s

judgment regarding the balance between benefits and

American Urological Association (AUA)

Renal Mass and

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risks/burdens (Table 2). Strong Recommendations are

directive statements that an action should (benefits

outweigh risks/burdens) or should not (risks/burdens

outweigh benefits) be undertaken because net benefit

or net harm is substantial. Moderate Recommendations

are directive statements that an action should (benefits

outweigh risks/burdens) or should not (risks/burdens

outweigh benefits) be undertaken because net benefit

or net harm is moderate. Conditional Recommendations

are non-directive statements used when the evidence

indicates that there is no apparent net benefit or harm

or when the balance between benefits and risks/burden

is unclear. All three statement types may be supported

by any body of evidence strength grade. Body of

evidence strength Grade A in support of a Strong or

Moderate Recommendation indicates that the statement

can be applied to most patients in most circumstances

and that future research is unlikely to change

confidence. Body of evidence strength Grade B in

support of a Strong or Moderate Recommendation

indicates that the statement can be applied to most

patients in most circumstances but that better evidence

could change confidence. Body of evidence strength

Grade C in support of a Strong or Moderate

Recommendation indicates that the statement can be

applied to most patients in most circumstances but that

better evidence is likely to change confidence. Body of

evidence strength Grade C is only rarely used in

support of a Strong Recommendation. Conditional

Recommendations can also be supported by any

evidence strength. When body of evidence strength is

Grade A, the statement indicates that benefits and

risks/burdens appear balanced, the best action depends

on patient circumstances, and future research is

unlikely to change confidence. When body of evidence

strength Grade B is used, benefits and risks/burdens

appear balanced, the best action also depends on

individual patient circumstances and better evidence

could change confidence. When body of evidence

strength Grade C is used, there is uncertainty regarding

the balance between benefits and risks/burdens,

alternative strategies may be equally reasonable, and

better evidence is likely to change confidence.

Where gaps in the evidence existed, the Panel provides

guidance in the form of Clinical Principles or Expert

Opinion with consensus achieved using a modified

Delphi technique if differences of opinion emerged.

Clinical Principle is a statement about a component of

clinical care that is widely agreed upon by urologists or

other clinicians for which there may or may not be

evidence in the medical literature. Expert Opinion refers

to a statement, achieved by consensus of the Panel,

that is based on members' clinical training, experience,

knowledge, and judgment for which there is no

evidence.

Process

The Renal Mass and Localized Renal Cancer Panel was

created in 2014 by the American Urological Association

Education and Research, Inc. (AUA). The Practice

Guidelines Committee (PGC) of the AUA selected the

Panel Chair who in turn appointed the Vice Chair. In a

collaborative process, additional Panel members,

including additional members of the College of

American Pathologists (CAP), Society of Urologic

Oncology (SUO), American College of Radiology (ACR),

American Society of Nephrology (ASN), Endourological

Society, and Society of Interventional Radiology (SIR)

with specific expertise in this area, were then

nominated and approved by the PGC. The AUA

conducted a thorough peer review process. The draft

guidelines document was distributed to 124 peer

reviewers, 54 of which submitted comments. The Panel

reviewed and discussed all submitted comments and

revised the draft as needed. Once finalized, the

guideline was submitted for approval to the PGC and

Science and Quality Council. Then it was submitted to

the AUA, CAP, SUO, ACR, ASN, Endourological Society,

and SIR Board of Directors for final approval. Panel

members received no remuneration for their work.

A Renal Mass amendment panel consisting of five

members was created in August 2020 to conduct an

update to the Renal Mass and Localized Renal Cancer

guideline. They were also tasked with integrating the

Follow-Up for Clinically Localized Renal Neoplasms

guideline from 2013 into the Renal Mass and Localized

Renal Cancer guideline from 2017 to create one

cohesive document on management and follow-up on

renal mass. The panel consisted of members from both

the Follow-Up for Clinically Localized Renal Neoplasms

guideline and the Renal Mass and Localized Renal

Cancer guideline with an additional new member who

has not previously served on one of these panels. The

AUA conducted a thorough peer review process. The

draft guidelines document was distributed to 75 peer

reviewers, 21 of which submitted comments. The Panel

reviewed and discussed all submitted comments and

revised the draft as needed. Once finalized, the

guideline was submitted for approval to the PGC and

Science and Quality Council and the AUA Board of

Directors for final approval. Panel members received no

remuneration for their work.

BACKGROUND

Renal masses are a biologically heterogeneous group of

tumors ranging from benign masses to cancers that can

be indolent or aggressive.

7,8

The true incidence of renal

masses (including benign masses) is unknown.

However, benign masses comprise approximately 15-20

percent of surgically resected tumors < 4 cm and allow

estimations of benign incidence based on kidney cancer

statistics.

7,9,10

The vast majority (greater than 90%) of

kidney cancers in the United States are renal cortical

tumors known as RCC.

Epidemiology: United States

It is estimated there will be over 73,000 new cases of

kidney cancer in the United States in 2020.

11,12

The

incidence of kidney cancer has been increasing steadily

since the 1970’s in part due to more prevalent use of

axial imaging (CT and MRI).

In the United States,

over the past decade, the incidence of kidney cancer

continues to increase but at a much smaller increment,

approximately 1% per year. The greatest increase in

incidence has been in small, clinically localized renal

masses which now represent at least 40 percent of

incident tumors.

14,15

The overall survival rate for all stages of renal cancer is

approximately 74%, leaving an estimated 400,000

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

TABLE 2: AUA Nomenclature Linking Statement Type to Level of Certainty, Magnitude of Benefit or

Risk/Burden, and Body of Evidence Strength

Evidence Strength A

(High Certainty)

Evidence Strength B

(Moderate Certainty)

Evidence Strength C

(Low Certainty)

Strong

Recommendation

(Net benefit or harm sub-

stantial)

Benefits > Risks/Burdens

(or vice versa)

Net benefit (or net harm)

is substantial

Applies to most patients

in most circumstances

and future research is

unlikely to change confi-

dence

Benefits > Risks/Burdens

(or vice versa)

Net benefit (or net harm)

is substantial

Applies to most patients

in most circumstances but

better evidence could

change confidence

Benefits > Risks/Burdens (or

vice versa)

Net benefit (or net harm)

appears substantial

Applies to most patients in

most circumstances but bet-

ter evidence is likely to

change confidence

(rarely used to support a

Strong Recommendation)

Moderate

Recommendation

(Net benefit or harm

moderate)

Benefits > Risks/Burdens

(or vice versa)

Net benefit (or net harm)

is moderate

Applies to most patients

in most circumstances

and future research is

unlikely to change confi-

dence

Benefits > Risks/Burdens

(or vice versa)

Net benefit (or net harm)

is moderate

Applies to most patients

in most circumstances but

better evidence could

change confidence

Benefits > Risks/Burdens (or

vice versa)

Net benefit (or net harm)

appears moderate

Applies to most patients in

most circumstances but bet-

ter evidence is likely to

change confidence

Conditional

Recommendation

(No apparent net benefit

or harm)

Benefits = Risks/Burdens

Best action depends on

individual patient circum-

stances

Future research unlikely

to change confidence

Benefits = Risks/Burdens

Best action appears to

depend on individual pa-

tient circumstances

Better evidence could

change confidence

Balance between Benefits &

Risks/Burdens unclear

Alternative strategies may

be equally reasonable

Better evidence likely to

change confidence

Clinical Principle

A statement about a component of clinical care that is widely agreed upon by urolo-

gists or other clinicians for which there may or may not be evidence in the medical

literature

Expert Opinion

A statement, achieved by consensus of the Panel, that is based on members' clinical

training, experience, knowledge, and judgment for which there is for which there may

or may not be evidence in the medical literature

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

kidney cancer survivors in the United States as of

2013.

However, approximately 14,800 men and

women will die of kidney cancer in 2020.

The

mortality from kidney cancer has been steadily

decreasing, approximately 1% per year, since 2004.

16,17

Reasons for this decrease are multifactorial.

Kidney cancer is more common in men than women,

and more common in African Americans, American

Indian and Alaska Native populations than

Caucasians.

The median age at diagnosis is 64 years

old, although kidney cancer can present at any age.

Epidemiology: Global and International

Considerations

Over 300,000 men and women are diagnosed with

kidney cancer around the world each year and

approximately 150,000 patients will die of disease.

The incidence of kidney cancer varies dramatically

around the world with the developed countries having

the highest rates.

Incidence rates have increased in

both sexes and are most notable in the elderly

population (greater than 75 years of age). Mortality

rates have been stable in most countries but have been

decreasing by 1 to 3 percent in Western and Northern

Europe, the United States, and Australia. The improved

mortality globally and in the US is attributed to

decreased smoking rates, improved therapies, and

access to medical care. The decrease in mortality has

been faster in women than in men and overall mortality

rates remain higher in men than women.

Etiology

There are a number of established and putative risk

factors for RCC. Smoking is a well-established risk

factor, accounting for 20 percent of incident cases and

increasing the risk of RCC by 50 percent in men and 20

percent in women., Obesity is associated with 30% of

incident cases of RCC and each 5 kg/m2 increase in

body mass index increases the risk of RCC by 24

percent in men and 34 percent in women.

23-25

Interestingly, an “obesity paradox” exists in kidney

cancer – where obese patients are more likely to

develop RCC, but these tumors are more likely to be

low-grade, early stage tumors.

25-27

Hypertension is also

associated with increased risk of RCC.

23,28,29

The role of

CKD as a risk factor is controversial; however, patients

on maintenance dialysis are also reported to have an

increased risk of RCC.

The data regarding

environmental and occupational exposures are

inconsistent with the exception of chlorinated

solvents.

23,31

Moderate alcohol intake,

32,33

consumption of fruits and

(cruciferous) vegetables,

2,3,34,35

and a diet rich in fatty

fish

are believed to reduce the risk of RCC. Other

studies suggest that non-steroidal anti-inflammatory

agents and dietary factors do not play a role in the

etiology of RCC.

5,23,37

Hereditary and Familial RCC

Family history is associated with an increased risk of

RCC and a number of familial RCC syndromes are now

well-established, accounting for approximately 4-6% of

cases of RCC overall.

These syndromes include von

Hippel-Lindau (VHL), hereditary papillary renal

carcinoma (HPRC), Birt Hogg-Dubé (BHD), hereditary

leiomyomatosis RCC (HLRCC), succinate dehydrogenase

deficiency RCC, tuberous sclerosis, BAP-1 tumor

predisposition syndrome, and PTEN hamartoma tumor

syndrome (Cowden syndrome). Most of these

syndromes have associated tumors or benign findings

in other organ systems. RCC in these syndromes tends

to be earlier in onset and multifocal and management

should prioritize nephron-sparing approaches, including

tumor enucleation when feasible to optimize

preservation of parenchymal mass. For most of these

syndromes, tumors can be observed if less than 3 cm

as the risk of metastases remains low in this setting.

HLRCC and succinate dehydrogenase deficiency RCC

are the exception as tumors in these syndromes are

often very aggressive and a proactive approach to

evaluation and management should be pursued.

Genetic counseling should also be strongly

recommended for patients suspected of having familial

RCC, as it may allow for more intensive evaluation of

the patient for RCC and associated manifestations and

identification of blood relatives that may be at

syndromic risk.

Major Pathological Subtypes

Renal tumors are classified based on cell of origin and

morphologic appearance with renal adenocarcinoma

being the most common malignant tumor. Major sub-

classifications of RCC include clear cell, papillary,

chromophobe, collecting duct and unclassified RCC.

number of uncommon or rare subtypes exist including

but not limited to acquired cystic disease-associated

RCC, clear cell (tubulo) papillary, and renal medullary

carcinoma, which is an aggressive variant typically seen

in patients with sickle cell trait. The most common

benign tumors of the kidney include oncocytoma and

angiomyolipoma (AML). An abbreviated version of the

2016 World Health Organization classification of renal

neoplasms is detailed in Table 3.

Presentation and Diagnosis

Presentation

The “classic triad” of symptoms associated with a

malignant renal mass include hematuria, flank pain and

abdominal mass. Symptoms associated with RCC are

often a result of local tumor growth, hemorrhage,

paraneoplastic symptoms, or metastatic disease and

are uncommon in patients with clinically localized

disease. In fact, less than 5 percent of patients in

contemporary series present with these symptoms and

greater than 50 percent of renal masses are diagnosed

incidentally during an evaluation for unrelated signs or

symptoms.

42,43

Diagnosis

Physical examination has a limited role in the diagnosis

of clinically localized disease. However, physical

examination may have value in distinguishing the signs

and symptoms of advanced disease. For instance,

paraneoplastic syndromes (i.e. hypertension,

polycythemia, hypercalcemia) are present in

approximately 10-20 percent of patients with

metastatic RCC.

6,7,44

Importantly, physical examination

of patients with localized disease may occasionally

reveal unsuspected adenopathy, varicocele or medical

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

conditions that influence management decisions

including body habitus, prior abdominal scars, stigmata

of CKD, etc. In addition, careful physical examination

may also reveal findings suggestive of familial disease,

such as dermatologic lesions.

TABLE 3. Modified 2016 World Health

Organization classification of renal neoplasms

with focus on adult neoplasms.

Renal cell tumors

Clear cell RCC

Multilocular cystic renal neoplasm of low malignant

potential

Papillary RCC

HLRCC

Chromophobe RCC

Collecting duct carcinoma

Renal medullary carcinoma

MiT Family translocation carcinomas

Succinate dehydrogenase (SDH) deficient RCC

Mucinous tubular and spindle cell carcinoma

Tubulocystic RCC

Acquired cystic disease associated RCC

Clear cell papillary RCC

RCC, unclassified

Benign renal tumors

Papillary adenoma

Oncocytoma

AML

Metanephric adenoma and other metanephric tu-

mors

Adult cystic nephroma

Mixed epithelial stromal tumors

Juxtaglomerular cell tumor

Mesenchymal tumors

Leiomyosarcoma (including renal vein) and other

sarcomas

Leiomyoma and other benign mesenchymal tumors

Others

Adult Wilms tumor

Primitive neuroectodermal tumor

Metastatic tumors, lymphoma, leukemia

Laboratory Evaluation

There are no biomarkers or routine laboratory tests

used to diagnose renal malignancies. As such,

laboratory tests are useful in the assessment of renal

function (GFR) and for completeness of metastatic

evaluation. Routine laboratory tests for renal mass

evaluation include complete metabolic panel, complete

blood count, and urinalysis.

Imaging Techniques

Pre and post contrast-enhanced axial imaging, either

CT or MRI, is the ideal imaging technique for the

diagnosis and staging of clinically localized renal

masses. Masses initially diagnosed by US or

intravenous pyelography should be confirmed with pre/

post contrast-enhanced imaging. Depending on tumor

size, 20 to 30 percent of clinically localized renal

masses may be benign.

7,10

Patient and tumor

characteristics can indicate populations more or less

likely to harbor benign or malignant disease. For

instance, women with smaller tumors have a higher

likelihood of having benign tumors.

9,45,46

However, with

the exception of fat-containing AML, none of the current

imaging modalities can reliably distinguish between

benign and malignant tumors or between indolent and

aggressive tumor biology.

Contrast-enhanced abdominal imaging (CT or MRI) best

characterizes the mass, provides information regarding

renal morphology (of the affected and unaffected

kidney), assesses extrarenal tumor spread (venous

invasion or regional lymphadenopathy) and evaluates

the adrenal glands and other abdominal organs for

visceral metastases. Based on the most recent

consensus statement from the ACR and the National

Kidney Foundation, patients with acute kidney injury or

CKD and GFR less than 30 mL/min/1.73m

who are not

undergoing renal replacement therapy should receive

intravenous normal saline prophylaxis prior to receiving

iodinated contrast media.

Patients with GFR of 30-44

mL/min/1.73m

may be considered for intravenous fluid

prophylaxis per individual physician discretion based on

the patient’s risk factor for renal injury. However, MRI

with second generation gadolinium-based intravenous

contrast is now a safer option in many patients with

severe CKD, as outlined below.

The association of gadolinium-based MRI contrast

agents with the development of nephrogenic systemic

fibrosis – a devastating and potentially fatal condition

has been a concern for many years. More recently,

however, with newer group II and III gadolinium-based

contrast media the risk is felt to be lower than

previously perceived. The most recent consensus

statement from the ACR and the National Kidney

Foundation suggests that such agents can be given to

patients with a GFR under 30 mL/min/1.73m

recent systematic review of the risks of NSF in patients

with CKD 4 and 5 noted that the risks of NSF using

group II gadolinium-based agents was less than 0.07%.

Current ACR guidelines on the use of contrast media

state that patients need not be screened for renal

function prior to receiving group II gadolinium-based

agents. Non-contrast CT, MRI (with diffusion weighted

images) and US (with Doppler and with or without

microbubbles) can also be used to characterize renal

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

masses in patients who cannot receive conventional

intravenous contrast.

In general, solid renal masses that enhance greater

than 15-20 HU with intravenous contrast and do not

exhibit fat density should be considered suspicious for

RCC. Approximately 5-10% of AML’s are fat poor and

difficult to identify on imaging. Fat poor AML’s often

demonstrate suggestive features such as high

attenuation on unenhanced CT, homogeneous

enhancement on CT, or hypointensity on T2-weighted

MR, but the diagnosis remains difficult. Complex cystic

renal masses that have thickened irregular walls or

septa in which measurable enhancement is present are

classified as Bosniak 3. Approximately 50% of such

lesions prove to be malignant on final pathology.

Bosniak 4 complex cystic lesions are very suspicious for

malignancy as they contain enhancing nodular soft

tissue components and about 75-90% of such lesions

prove to be RCC on final pathology. This guideline

focuses primarily on the evaluation and management of

clinically localized sporadic renal masses suspicious for

RCC in adults, including solid enhancing renal tumors

and Bosniak 3 and 4 cystic renal masses.

In patients with RCC or suspicion of RCC, complete

staging is typically finalized with chest radiography

(CXR) or chest CT. Chest CT scan should be obtained

selectively, primarily for patients with pulmonary

symptoms or abnormal CXR, or for patients with high-

risk disease.

49,50

Bone scans should be reserved

primarily for patients with bone pain or elevated

alkaline phosphatase and brain imaging for those with

neurologic symptoms.

51-53

PET scan has a very limited

role in the routine evaluation or staging of RCC.

Renal Mass Biopsy

RMB currently has an adjunctive role in the diagnosis

and risk stratification of patients with renal masses

suspicious for renal cancer. Biopsy, or FNA, was

traditionally reserved for patients suspected of having

metastasis of another primary to the kidney, abscess,

or lymphoma, or when needed to establish a pathologic

diagnosis of RCC in occasional patients presenting with

disseminated metastases or unresectable primary

tumors. The role of RMB for clinically localized RCC has

evolved considerably over the past few decades with

substantial variance in practice patterns.

Tumor Characteristics

Staging

Kidney cancer is staged both clinically and

pathologically using the staging system outlined by the

American Joint Committee on Cancer (AJCC), also

known as the tumor node metastases (TNM)

classification.

The AJCC TNM Staging System for

Kidney Cancer is detailed in Table 4. Stage I and II

tumors include cancers of any size that are confined to

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

Primary Tumor (T)

TX Primary tumor cannot be assessed.

T0 No evidence of primary tumor.

T1 Tumor ≤7 cm in greatest dimension, limited to the kidney.

T1a Tumor ≤4 cm in greatest dimension, limited to the kidney.

T1b Tumor >4 cm but not >7 cm in greatest dimension, limited to the kidney.

T2 Tumor >7 cm in greatest dimension, limited to the kidney.

T2a Tumor >7 cm but ≤10 cm in greatest dimension, limited to the kidney.

T2b Tumor >10 cm, limited to the kidney.

T3 Tumor extends into major veins or perinephric tissues but not into the ipsilateral adrenal gland

and not beyond Gerota’s fascia.

T3a Tumor extends into the renal vein or its segmental branches, or invades the pelvicaliceal system,

or invades perirenal and/or renal sinus fat but not beyond Gerota’s fascia.

T3b Tumor grossly extends into the vena cava below the diaphragm.

T3c Tumor grossly extends into the vena cava above the diaphragm or invades the wall of the vena

cava.

T4 Tumor invades beyond Gerota’s fascia (including contiguous extension into the ipsilateral adrenal

gland).

Regional Lymph Nodes (N)

NX Regional lymph nodes cannot be assessed.

N0 No regional lymph node metastasis.

N1 Metastases in regional lymph node(s).

Distant Metastasis (M)

M0 No distant metastasis.

M1 Distant metastasis.

TABLE 4. The AJCC TNM Staging System for Kidney Cancer.

Primary Tumor (T), Regional

Lymph Nodes (N) and Distant Metastases (M) are detailed in Table 4A; The Anatomic Stage/

Prognostic Groups are detailed in Table 4B.

the kidney. This guideline statement identifies patients

with renal masses suspicious for clinical stage I and II

RCC, recognizing that a certain number of patients will

be upstaged. Stage III tumors are either locally

invasive (T3) or have involved lymph nodes (N1). Stage

IV tumors have spread beyond the kidney into adjacent

organs by direct invasion (T4) or distant metastases

(M1). Prognosis is best predicted by stage with cancer-

specific survival rates that approximate 85-90% for

clinically localized (Stage I and II) RCC.

Grading

Historically, a number of grading systems existed and

evolved to describe tumor differentiation, cytologic

aggressiveness, and prognosis of RCC based on nuclear

size and irregularity. In 1982, the Fuhrman Grading

system was described and became the most widely

used grading system for RCC.

In 2012, the

International Society of Urological Pathology (ISUP)

Grading System for RCC was proposed and was

updated in 2016.

41,56

The ISUP Grading System

incorporates aspects of the Fuhrman Grading system

but includes more objective criteria for nuclear

characteristics. In addition, sarcomatoid and rhabdoid

tumors, tumors with giant cells, and tumors with

extreme nuclear pleomorphism are included within

grade 4 tumors. Chromophobe RCC is no longer graded

in the ISUP system. In general, higher grade is

associated with larger tumor size and more aggressive

tumors.

57,58

Other Prognostic Indicators and Nomograms

Other factors for prognostic consideration include tumor

size, necrosis, sarcomatoid features, collecting system

invasion, patient symptoms, signs of paraneoplastic

syndromes, and performance status. Tumor size is

important for risk stratification regarding the likelihood

of malignancy and more aggressive pathology.

7,10,46

Various algorithms including the UCLA Integrated

Staging System (UISS),

59,60

Stage, Size, Grade and

Necrosis (SSIGN) score,

61-63

and other nomograms

8,9,64

incorporate a variety of pathological and patient

characteristics in an effort to improve prognostication.

Other Clinical and Biological Indicators

A number of molecular studies and markers have been

proposed for diagnostic and prognostic purposes in

RCC. The AHRQ Systematic Review identified a number

of biomarkers and laboratory tests that may have

diagnostic or prognostic utility in the renal cancer

literature.

However, these studies were often

univariable in design and therefore excluded from

analysis due to a failure to include clinical variables or

suboptimal methodology to validate the ultimate value

of the tests. Therefore, the AHRQ report identified

clinical and biological indicators as a major research

gap in the renal cancer literature.

Of note, urine aquaporin-1 and perilipin-2 were

identified as emerging biomarkers with potential for the

diagnosis of RCC.

10,11,67,68

Carbonic anhydrase-9 (CAIX)

expression is governed by the transcription factor

hypoxia-inducible factor-1α (HIF-1α), a well-known

component of the VHL pathway of clear cell RCC.

While CAIX expression on primary tumors is a

prognostic factor, especially in patients with metastatic

RCC, high and homogenous levels of CAIX expression

prevent risk stratification and clinical utility beyond the

established clinical predictors of aggressive, clear cell

RCC.

Serum tests including C-reactive protein and

platelet count may have prognostic roles, but further

investigation is needed. New imaging modalities,

including molecular imaging techniques using CAIX

71-73

or 99m technetium-sestamibi

single photon emission

CT, may help to better differentiate between malignant

and benign pathology. However, most markers and

imaging modalities in this domain are best

characterized as investigational.

Overview of Treatment Alternatives

A number of strategies exist for the management of

sporadic renal masses suspicious for clinically localized

renal cancer. Four strategies are considered standards

of care and include AS, RN, PN, and TA.

Active Surveillance (AS)

A growing body of literature exists regarding AS for

patients with clinically localized small renal masses

(cT1a, ≤4cm). A number of retrospective studies and

meta-analyses evaluate the safety of AS and quote the

risk of metastatic progression while on AS to be less

than 2 percent in well selected patients over the initial

3 years of AS.

75-77

Two large prospective AS programs

have been initiated that follow patients with serial

imaging, and both report slow growth rates and

extremely low rates of metastatic progression, albeit

with relatively short follow-up.

78-80

Both programs

screen patients with an initial metastatic evaluation

including serum laboratory evaluation and chest

imaging. Patients are then evaluated every 3-6 months

for two years and with extended imaging intervals

beyond that. Rates of biopsy are variable with one

group utilizing RMB in greater than 50 percent of the

cohort and the other using biopsy in less than 10

percent of its patients. Further data with longer follow-

up from these cohorts will help to inform the utility of

AS in the small renal mass population, and should allow

for more intelligent patient selection for AS. Of note,

the Delayed Intervention and Surveillance for Small

Renal Masses (DISSRM) Registry prospectively

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

TABLE 4B.

Stage T N M

I T1 N0 M0

II T2 N0 M0

III T1 or T2 N1 M0

T3 N0 or N1 M0

IV T4 Any N M0

Any T Any N M1

catalogues a contemporaneous cohort of patients

undergoing AS and primary intervention and will offer

data regarding comparative effectiveness.

Radical Nephrectomy (RN)

RN was the mainstay of therapy for all renal masses for

many decades. Historically, RN included the removal of

the entire kidney including Gerota's/Zuckerkandel's

fascia, regional lymph nodes and the adrenal gland. RN

can be performed through an open incision or via

minimally-invasive approaches (laparoscopic or

robotic). Cancer-specific survival associated with RN is

excellent; however, recent controversies regarding RN

include its negative impact on renal function and

historical overutilization for the management of stage I,

especially T1a, tumors.

Partial Nephrectomy (PN)

PN is widely accepted as a nephron-sparing approach to

the management of clinically localized RCC. Initially

underutilized and predominantly performed in large

academic centers,

12,13,81

the management of clinically

localized renal masses by PN has expanded with

implementation of guideline statements and the

expansion of robotic technology.

14,15,82

PN can be

performed through an open incision or via a minimally

invasive approach, although the robotic approach has

largely supplanted laparoscopic surgery as the

preferred minimally invasive approach.

The benefit of

PN lies in the potential to preserve renal function but

this is counterbalanced by an increased risk of urologic

complications, although most are manageable and

typically associated with good outcomes. Recent

controversies surround modifiable and non-modifiable

factors during surgery to improve renal functional

outcomes, including parenchymal volume preservation,

warm versus cold ischemia, and duration of ischemia.

Thermal Ablation (TA)

TA techniques were developed in an effort to improve

patient procedural tolerance and reduce the potential

for complications from PN, while still preserving renal

function. A multitude of techniques/technologies have

been investigated to ablate renal tumors; however, RFA

and cryoablation have been most widely investigated

and integrated into clinical practice. While the

superiority of RFA or cryoablation remains

controversial, it is generally accepted that oncologic

outcomes are similar for both approaches.

84-86

TA has

traditionally been performed through a variety of

approaches, including open, laparoscopic, and

percutaneous. Concerns with the TA literature included

relatively limited follow-up, lack of pre and post

treatment biopsy to define malignancy and efficacy,

and increased local recurrence rates relative to surgical

excision. The latter require a longer period of

surveillance (5 years) with cross-sectional imaging to

monitor for late local recurrences.

Investigational Modalities

Other technologies including high-intensity focused US

(HIFU), radiosurgery, microwave therapy, pulsed

cavitational US, and laser thermal therapy remain

investigational at this time.

Follow-up After Intervention

The prognosis of patients treated with surgery or

thermal ablation for kidney cancer is primarily

determined by tumor stage, with tumor size, grade,

histology, with a variety of other contributing

factors.

61,62,87-93

Several algorithms and prognostic

models have been published, yet a recent analysis of

outcomes from a phase III randomized adjuvant clinical

trial suggested that these models only marginally

outperformed stage alone.

Current surveillance and survivorship strategies for

patients with RCC have incorporated clinical history,

physical examination, relevant laboratory testing, and

abdominal and chest imaging.

95,181,387

This allows for

assessment of potential complications or sequelae of

intervention, functional recovery, and evaluation for

common sites of recurrence, including those in the

lungs, liver, adrenal glands, and other retroperitoneal

sites. Cross-sectional imaging is generally preferred,

particularly for high-risk patients, while abdominal

ultrasound or chest radiography can be considered in

lower-risk patients or as a potential alternative during

long-term surveillance. Approximately thirty-percent of

recurrences have been diagnosed after 5 years in some

series, emphasizing the need to consider longer follow-

up than advocated in most current surveillance

protocols.

Bone metastasis are only rarely identified

during surveillance in the absence of bone pain, an

elevated alkaline phosphatase, or radiographic findings

suggesting a bony neoplasm, and bone scan can

generally be reserved for these indications.

96-99

Patients

with acute neurological signs/symptoms should undergo

prompt cross-sectional imaging of the brain and/or

spine,

370,371,372

but beyond this there is no role for

routine neurologic imaging in surveillance of patients

with localized renal cancer. Additional site-specific

imaging should be ordered as warranted by clinical

signs/symptoms suggestive of recurrence or metastatic

spread. Current data do not support the use of PET

scan in the routine surveillance of patients with renal

cancer, and this test should only be considered

selectively, such as for trouble-shooting when other

tests are concerning but inconclusive.

373

There are no prospective data to compare currently

available surveillance strategies, resulting in substantial

variability in the approach, modality, frequency, and

duration of follow-up after intervention. The premise of

early detection of tumor recurrence after primary

intervention is that this approach will result in patient

cure, improved survival, or appropriate palliation. In

addition, surveillance allows the urologist to provide a

measure of reassurance to the patient who is worried

about cancer recurrence. Surveillance also offers the

opportunity to monitor treatment effects and address

survivorship issues that might arise. Taking all of these

considerations into account, the Panel updated the

follow-up strategies after intervention to strike a useful

and measured balance.

GUIDELINE STATEMENTS

INITIAL EVALUATION AND DIAGNOSIS

Evaluation

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

1. In patients with a solid or complex cystic

renal mass, clinicians should obtain high

quality, multiphase, cross-sectional abdominal

imaging to optimally characterize and

clinically stage the renal mass.

Characterization of the renal mass should

include assessment of tumor complexity,

degree of contrast enhancement (where

applicable), and presence or absence of fat.

(Clinical Principle)

Multiphase cross-sectional imaging to assess

enhancement characteristics and the biological potential

of a renal mass should be obtained. The added value of

cross-sectional imaging is to assess for regional tumor

involvement or abdominal metastases, and to exclude

benign AML, which may be distinguished by the

presence of intra-lesional fat.

100

This may be done by

CT or MRI.

101

In rare instances RCC may demonstrate

macroscopic or microscopic fat density on imaging and

even pathologically, but this is the exception rather

than the rule.

102

The risks and benefits of the diagnostic

study should be considered, including risks of radiation

exposure (CT) and contrast administration including

contrast-induced nephropathy or allergic reactions.

Patients with eGFR <45 mL/min/1.73m

undergoing CT

with intravenous contrast should be considered for peri-

procedural hydration. Administration of intravenous

contrast should be avoided if possible in patients with

severe CKD who are nearing dialysis. Administration of

intravenous contrast can be used judiciously in patients

on hemodialysis and timed just prior to receiving

dialysis in coordination with nephrology. MRI is

appropriate for patients with contraindications to

iodinated contrast and may provide improved

characterization of small renal tumors, particularly

those less than 2 cm in diameter.

103

The risks of

gadolinium based contrast agents (GBCA) in patients

with altered renal function have been of great interest

since the description of Nephrogenic Systemic Fibrosis,

a potentially lethal fibrosing dermopathy associated

with soft tissue deposition and accumulation of

gadolinium. The risk appears related to the isoform of

gadolinium used with group I GBCA agents having the

highest risk while group II GBCA are associated with

few if any unfounded cases of NSF. A recent systematic

review focused on patients with CKD 4 and 5

reported that the incidence of NSF in this

population was less than 0.07% with second

generation gadolinium agents. Current ACR

guidelines on the use of contrast media state that

patients need not be screened for renal function

prior to receiving group II GBCA, which are now

considered safe at any level of eGFR.

Criteria for suspicion of RCC are enhancement of

greater than 15-20 Hounsfield Units on CT or > 20% on

MRI. Adjunctive techniques on MRI can also be utilized

to assess relative risk of malignancy.

101,103

Complex cystic renal masses that have somewhat

thickened irregular walls or septa with measurable

enhancement are classified as Bosniak 3, and

approximately 50% of such lesions are malignant.

Bosniak 4 complex cystic lesions have enhancing

nodular soft tissue components and about 75-90% are

malignant.

104

The recognition that cystic renal masses,

when compared with solid masses, are more likely to

be benign and when malignant less aggressive, has led

to a recent proposed update to the Bosniak

Classification. The update is intended to reduce

interreader variability, improve the precision of

reported malignancy rates, and incorporate MRI into

the classification system.

105

Doppler US and contrast-enhanced US using

microbubbles may also be considered in select patients

in whom other forms of intravenous contrast are

contraindicated. As of 2017, contrast-enhanced US is

approved for assessment of hepatic lesions and can be

considered for off-label use for renal mass

evaluation.

106,107

Imaging should comment on renal mass diameter in

cranio-caudal, transverse, and anterio-posterior

dimensions, tumor morphology, involvement of or

juxtaposition to the renal hilum, vein, or collecting

system, and associated features such as retroperitoneal

lymphadenopathy and presence or absence of

abdominal metastases.

108

Infiltrative growth pattern

can broaden the differential diagnosis and has

prognostic significance. While emerging data suggest

that clear cell RCC may be distinguished from the

papillary subtype by differences in enhancement

patterns, no definitive conclusion can be drawn

regarding biological potential based on enhancement

pattern alone. In addition, significant overlap can exist

in imaging characteristics of RCC and oncocytoma on

cross sectional imaging, or between subtypes of

papillary RCC.

108,109

Several algorithms which quantify aspects of renal

tumor morphometry have been developed to describe

tumor complexity including the relationship with the

renal hilum, collecting system, polarity, and endophytic

versus exophytic location. These systems include the

RENAL nephrometry score, the PADUA score, and the C

-index.

110-112

A number of studies suggest that such

categorization may be useful for selection of type of

surgery (RN or PN) or surgical approach (open or

minimally invasive) as well as provide an estimate of

the risk of surgical complications.

113-115

While some

reports suggest that increasing tumor complexity can

also correlate with aggressive histology or renal

functional outcomes following surgery, the utility of

these systems should be regarded primarily as an aide

for surgical selection and risk stratification for

postoperative complications.

116,117

2. In patients with suspected renal malignancy,

clinicians should obtain a comprehensive

metabolic panel, complete blood count, and

urinalysis. Metastatic evaluation should

include chest imaging to evaluate for possible

thoracic metastases. (Clinical Principle)

Laboratory and metastatic evaluations are important

aspects of the evaluation of the patient with a renal

mass suspicious for RCC. Urinalysis with dipstick and

microscopic evaluation should be obtained to assess for

proteinuria, hematuria, pyuria or signs of other

genitourinary maladies. Presence of proteinuria is an

important prognostic indicator and can be detected by

standard urine dipstick. Patients with a positive dipstick

test (1+ or greater) should undergo confirmation by a

American Urological Association (AUA)

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quantitative measurement (protein-to-creatinine ratio

or albumin-to-creatinine ratio), as part of a focused

medical workup for renal dysfunction.

118,119

The serum

creatinine level should be utilized to calculate an eGFR

by the Modification of Diet in Renal Disease or CKD-EPI

equations.

120,121

Please refer to subsequent statements

regarding patient counseling about functional status,

CKD classification, and management implications

(Guideline Statements 3, 7, 8, 14-17, and 19).

Microscopic hematuria, defined as greater than 3 RBC/

hpf, should also be further assessed to rule out a co-

existing urinary tract conditions.

122

The comprehensive

metabolic panel should be reviewed for electrolyte

abnormalities and hepatic functional parameters.

Abnormalities in hepatic synthetic function may prompt

further workup to exclude co-existing hepatic disease or

metastases which may impact surgical management or

overall prognosis.

123

The presence of elevated alkaline

phosphatase and/or bone pain should spur investigation

of potential bone metastases.

Complete blood count

should be considered prior to any intervention.

Initial evaluation of a patient with a renal mass

suspected of malignancy should also include chest

imaging, whether by CT or plain radiography. This is

based on the tumor biology of RCC, with the most

common site of metastatic disease being the chest.

124

While chest CT is more sensitive than plain

radiography, many nonspecific findings (post-

inflammatory or infectious) can also be detected.

Hence, chest imaging should be tailored to tumor risk

with chest radiography being adequate for lower risk

tumors and chest CT being more appropriate in the

setting of higher risk primary tumors (presence of

thrombi, presumed adenopathy, larger tumor size,

infiltrative appearance, or extensive tumor necrosis) or

for patients with relevant symptoms or physical

examination findings.

50,125

3. For patients with a solid or Bosniak 3/4

complex cystic renal mass, clinicians should

assign chronic kidney disease (CKD) stage

based on glomerular filtration rate (GFR) and

degree of proteinuria. (Expert Opinion)

CKD is highly prevalent (approximately 25-30%)

among patients with small renal masses. This

population shares common CKD risk factors including

older age, diabetes mellitus and hypertension.

126-133

All-

cause and cardiovascular mortality increases with CKD

in the general population according to severity of CKD

and even with presence of albuminuria alone.

134,135

Similar association of decreased GFR and/or

albuminuria with increased mortality has been observed

among patients with renal masses (clinical stage T1-

T3).

136

Therefore, identification and proper classification

of CKD as outlined in the Kidney Disease: Improving

Global Outcomes (KDIGO) Guidelines should be

performed. This takes into account: 1) GFR (CKD-EPI

GFR equation); 2) proteinuria; and 3) etiology of

CKD.

121

KDIGO is an independent international non-profit

organization which develops and implements kidney

disease guidelines. First established in 2003, guidelines

regarding CKD classification and management were last

updated in 2012. CKD is diagnosed when renal

functional pathology has persisted greater than 3

months as determined by structural or functional

abnormalities. Beyond identification of CKD, staging

allows for determination of prognosis and stage-related

CKD complications such as hypertension, anemia,

mineral bone disease, metabolic acidosis and

hypoalbuminemia.

137

Additionally, staging allows for

improved risk stratification, functional counseling and

informed decision making.

CKD staging

137

is as follows: 1) eGFR (mL/min/1.73m

)

> 90 = G1; G2, 60-89; G3a, 45-59; G3b, 30-44; G4,

15-29; G5 <15; and 2) Albuminuria (Albumin/

creatinine ratio, mg/g)- A1, <30; A2, 30-300; A3

>300. Note that A1 generally correlates with negative

or trace protein on dipstick. Prognosis of CKD is

illustrated in Figure 1.

Figure 1. KDIGO Classification of CKD Risk.

CKD-EPI creatinine clearance equation

(www.mdrd.com): 141 x min(SCr/k, 1)

x max(SCr/k,

-1.209

x 0.993

Age

x [1.018 if female] x [1.159 if black],

where SCr is serum creatinine (in mg/dL), k is 0.7 for

females and 0.9 for males, a is 0.329 for females and

0.411 for males, min is the minimum of SCr/k or 1, and

max is the maximum of SCr/k or 1.

121

Renal nuclear scintigraphy measures proportional flow

and function of each kidney which can help assess the

potential impact of renal resection (PN or RN) on global

functional outcomes. Care should be taken when

interpretting the results of renal nuclear scans as pre-

operative proportional GFR assessment may

underestimate actual post-operative GFR due to

technical aspects of scintigraphy, the presence of a

renal mass, hyperfiltration and compensation of the

remaining kidney.

138,139

Recent studies suggest that

differential parenchymal volume analysis may more

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accurately assess split renal function, similar to what is

done for renal donors.

163,272

Counseling

4. In patients with a solid or Bosniak 3/4

complex cystic renal mass, a urologist should

lead the counseling process and should

consider all management strategies. A

multidisciplinary team should be included

when necessary. (Expert Opinion)

Patients diagnosed with a localized renal mass should

have a urologist involved with their care in a leadership

role to help coordinate evaluation, counseling, and

management. Occasionally a multidisciplinary team is

required to further assess and manage the renal mass

based on specific factors.

Patients electing for RMB or percutaneous ablation may

be referred to an interventional radiologist.

Involvement of the urologist in the percutaneous

ablation or RMB procedure appears to depend on local

practice patterns. A survey of 124 academic institutions

in the United States revealed that urologists were

present at the time of percutaneous ablation alongside

the radiologist in 59% of the institutions surveyed.

140

The potential feasibility and safety of office-based US

guided RMB by the urologist has been reported;

however, the vast majority of RMBs are performed by a

radiologist.

141

Given the significant prevalance of CKD in patients with

renal masses that can be exacerbated by surgery or

other treatments, involvement of a nephrologist should

be selectively coordinated. In particular, referral to

nephrology should be considered for patients with eGFR

less than 45 mL/min/1.73m

, confirmed proteinuria,

diabetics with preexisting CKD, or whenever eGFR is

expected to be less than 30 mL/min/1.73m

after

intervention.

Utilization of RMB in an increasing number of patients

underscores the important role the pathologist plays to

establish an accurate diagnosis. For example, a biopsy

revealing an oncocytic neoplasm may prove to be

benign oncocytoma or an eosinophilic variant of one of

the many subtypes of RCC. Emerging work has

suggested that tissue based molecular markers may aid

in diagnosis or in assigning oncologic risk to a given

tumor.

142,143

Evaluation of the normal adjacent renal

parenchyma for nephrologic disorders can also greatly

enhance patient care. A dedicated pathologist, ideally

with GU subspecialty interest, can be of great value in

the evaluation and management of patients with

localized renal masses.

144-146

A medical oncologist can also be essential for the

management of some patients who present with

clinically localized renal masses, particularly when there

are considerations for neoadjuvant or adjuvant clinical

trials. If final pathology shows high risk or locally

advanced features, adjuvant therapy or clinical trials

should be considered. Additionally, at recurrence these

patients may require systemic therapy. The activity of

neoadjuvant systemic therapies to downsize localized

tumors has been documented in limited clinical

trials.

147,148

Such a strategy may prove helpful for

occasional patients where a nephron-sparing approach

is precluded due to unfavorable tumor size and location

and RN would leave the patient dialysis-dependent.

However, the overall utility of such an approach is

currently unknown.

It is estimated that 4-6% of patients with RCC have a

familial syndrome, and all patients with a renal mass 46

years of age or younger should be referred for genetic

counseling. Patients with multifocal and/or bilateral

renal masses and those with a personal or family

history of malignant or benign findings potentially

associated with the various familial RCC syndromes

should also be strongly considered for genetic

counseling regardless of age. Statement 9 provides

further details regarding specific recommendations for

genetic counseling.

5. Clinicians should provide counseling that

includes current perspectives about tumor

biology and a patient-specific risk assessment

inclusive of sex, tumor size/complexity,

histology (when obtained), and imaging

characteristics. For cT1a tumors, the low

oncologic risk of many small renal masses

should be reviewed. (Clinical Principle)

The current paradigms for patients with clinically

localized renal masses suspicious for malignancy cannot

reliably predict the presence of malignancy or

aggressive tumor biology prior to extirpative surgery.

This includes clinical predictors of malignancy,

adjunctive laboratory tests and RMB. The 2017 AHRQ

report and recent update systematically reviewed the

literature regarding clinical predictors of malignancy

and determined: (1) no composite model of clinical

parameters reliably predicts malignancy, (2) no single

predictive variable (i.e. age, sex) was uniformly

predictive of malignancy; and (3) male sex and

increasing tumor size indicate a higher likelihood of

malignancy.

In meta-analysis, male sex imparted a

nearly 3-fold increased risk of malignancy (effect size

2.71, 95% confidence interval 2.39-3.02) compared to

female sex. While benign histology is more common in

women, RCC still predominates in both genders. Across

several studies, tumor size imparted a 30% increased

risk of malignancy per centimeter increase in tumor

size (effect size 1.3 per cm increase in diameter, 95%

confidence interval 1.22-1.43).

These findings are

consistent with a wealth of retrospective literature

examining univariate predictors of benign and

malignant pathology in extirpative surgical series.

149

For

example Frank, et al. demonstrated that 46% of tumors

< 1cm are benign and only 2% are high-grade RCC in

contrast to 6% benign and 58% high-grade RCC for

tumors greater than 7 cm.

150

A systematic review by

Johnson et al. demonstrated a decreasing rate of

benign tumors with increasing tumor size from 40% at

1 cm to only 6% for tumors greater than 7 cm.

Importantly, many clinical T1a cancers (< 4

centimeters) demonstrate indolent tumor biology. In

retrospective extirpative surgical series, no patient with

a tumor less than 2 centimeters, and less than 2% of

patients with tumors 4 centimeters or smaller,

presented with or developed metastatic disease when

observed for a median of approximately 36 months.

8,125

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The indolent nature of many small and very-small renal

masses (less than 2 cm) is also supported by

prospective AS data, in which 1% or less of patients

progress to metastatic disease.

78,80

Although less robust evidence exists, data also suggest

that tumor architecture, complexity, and enhancement

patterns on imaging may predict malignancy. In the

AHRQ systematic review, solid tumor architecture

(versus cystic architecture) was associated with

malignancy.

Increasing tumor complexity (as reported

by the RENAL Nephrometry Score or similar

methodology) was also consistently associated with an

increasing risk of malignancy and aggressive tumor

biology; however, the heterogeneity of these data

prevents meaningful conclusions.

A number of studies

indicate that enhancement patterns are predictive of

tumor histology. While papillary RCC is often hypo-

enhancing, both malignant and benign masses can

display heterogeneous avid contrast enhancement

patterns.

109,151

More recent studies have demonstrated

that complex cystic masses, particularly Bosniak 3

category lesions and those that are predominantly

cystic, often have indolent tumor biology and favorable

outcomes on AS.

152-154

In summary, while no model of clinical parameters,

laboratory or radiographic test or RMB reliably predicts

malignancy or aggressive tumor biology, a number of

important pre-treatment parameters can be used to

advise patients about their risk of malignancy and

death from RCC.

Consultation should therefore include

a discussion of the influence of patient, imaging, and

tumor characteristics that may impact clinical decision

making. The indolent nature of many small, clinically

localized renal masses should also be reviewed when

relevant.

6. During counseling of patients with a solid or

Bosniak 3/4 complex cystic renal mass,

clinicians must review the most common and

serious urologic and non-urologic morbidities

of each treatment pathway and the

importance of patient age, comorbidities/

frailty, and life expectancy. (Clinical Principle)

The AHRQ report systematically reviewed over 100

manuscripts reporting on the efficacy, comparative

efficacy, and potential morbidities of the four major

management strategies (RN, PN, TA, and AS) for

clinically localized renal masses.

The analysis

determined that oncological outcomes are determined

primarily by tumor stage and are similar across

treatment options with the exception of TA. TA was

associated with inferior local recurrence free (LRFS)

survival for primary treatment but equivalent LRFS

following secondary treatments. There was no

significant difference in stage-specific outcomes for well

-selected patients undergoing any of the management

strategies, with the important caveat that the majority

of patients undergoing TA or AS had small renal masses

with less biological aggressiveness. A key finding in

reviewing these data is that overall survival is

determined primarily by age and risk of competing

comorbidities.

A number of retrospective analyses

confirm these findings, indicating that competing risk

mortality exceeds cancer-specific mortality for many

patients with clinically localized tumors, and that this is

largely driven by cardiovascular comorbidities.

-,,

Therefore, cancer-specific survival is primarily

determined by tumor characteristics and overall

survival is determined by patient age and competing

risk of comorbidities, specifically cardiovascular

comorbidity in the population with clinically localized

renal cancer.

Each management strategy for the solid or complex

cystic mass is associated with a unique profile of renal

functional outcomes, perioperative outcomes, potential

harms, and health-related quality of life. It should be

noted that each treatment strategy (RN, PN, or TA) has

similar rates of minor and major complications but a

unique profile of these complications that should be

discussed with patients.

Selection of a management

strategy should therefore take into account patient

preferences and prioritize potential harms associated

with each management strategy on an individual basis.

RN is associated w ith the greatest decrease

in GFR and highest risk of de novo CKD stage 3 or

higher. While these changes in GFR may be

clinically insignificant in patients with a normal

contralateral kidney, they warrant consideration

and discussion in certain patients. RN is associated

with favorable perioperative outcomes and a low

risk of urologic complications compared to PN.

The

favorable outcomes associated with RN may reflect

the high proportion of RN performed via the

minimally invasive approach.

PN offers excellent preservation of renal

parenchyma and GFR; however, it carries a higher

risk of blood transfusions and urologic complications

(e.g., urine leak) than other modalities. These

complications may subject a small proportion of

patients to additional treatments (e.g., ureteral

stents, abdominal drains, embolization of

pseudoaneurysm).

TA carries an inferior LRFS w hen considering

primary efficacy that may mandate secondary

interventions. In the AHRQ analysis,

TA had the

most favorable perioperative outcome profile and a

similar low risk of harms when compared to other

strategies. Success rates with TA are highest with

small peripheral tumors.

AS offers favorable oncologic and overall

survival outcomes in well-selected patients, albeit

in limited studies with relatively short to

intermediate-term follow-up.

78,80,159-161

AS foregoes

the operative risks associated with other

management strategies but potentially introduces

anxieties and oncologic risks not suitable for all

patients.

The AHRQ analysis and literature update was unable to

identify strong, consistent predictors of comparative

benefit among management strategies due to

heterogeneity and paucity of data, particularly in

treatments other than RN or PN.

Increasing age or

limited life expectancy is associated with lower

incidence of cancer-specific mortality independent of

management strategy. This phenomenon is most robust

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in patients greater than 75 years of age, where the

comparative benefits of intervention and subsequent

detriments of decreases in GFR are more difficult to

quantify. Therefore, it is impossible to make a blanket

statement that one management strategy is preferred

based on patient age, comorbidities, frailty, and/or life

expectancy, but all should be considered during

individualized counseling.

7. Clinicians should review the importance of

renal functional recovery related to renal

mass management, including the risks of

progressive CKD, potential short- or long-term

need for renal replacement therapy, and long-

term overall survival considerations. (Clinical

Principle)

Individuals with localized renal masses have a high

burden of CKD to begin with, partially because this

population shares risk factors that are common to CKD.

They tend to be older with high prevalence of diabetes

mellitus (10-20%) and hypertension (25-50%). Poorly

controlled diabetes mellitus and hypertension can

induce hyperfiltration and glomerular hypertension

resulting in CKD or exacerbation of CKD leading to

further loss of function. After surgical resection, CKD

prevalence and degree further increases.

126-129,162

Most

studies suggest that patients with CKD due to medical

etiologies have reduced overall survival and are at

increased risk for cardiovascular events. Patients with a

renal mass and preexisting CKD are at increased risk

for progressive decline in renal function after surgery

and also may experience increased mortality rates.

However, recent studies suggest that patients with CKD

that is primarily due to surgical removal of nephrons,

rather than medical causes, may have better outcomes,

as long as the new baseline GFR is greater than 45 mL/

min/1.73m

163,164

Almost all studies in this domain are

retrospective and further investigation is required.

165

8. Clinicians should consider referral to

nephrology in patients with a high risk of CKD

progression, including those with estimated

glomerular filtration rate (eGFR) less than 45

mL/min/1.73m

, confirmed proteinuria,

diabetics with preexisting CKD, or whenever

eGFR is expected to be less than 30 mL/

min/1.73m

after intervention. (Expert

Opinion)

Predictive factors for post-operative development of

CKD or progression of pre-existing CKD include older

age, diabetes mellitus (DM), hypertension (HTN), as

well as male sex, obesity, tobacco use, larger tumor

size, and post-operative acute kidney injury.

128,133,166-170

Patients who present with eGFR less than 45 mL/

min/1.73m

or confirmed proteinuria are at particularly

high risk from a functional standpoint, and should be

considered for nephrology consultation. Patients who

are expected to have an eGFR less than 30 mL/

min/1.73m

after intervention will also be at high risk

long-term, and a nephrologist should be involved in

their care. Identifying modifiable risk factors including

DM, HTN and smoking is essential. Optimizing glycemic

and blood pressure control, smoking cessation and

minimizing risk of acute kidney injury (with avoidance

of hypotension and nephrotoxic agents such as

intravenous contrast or non-steroidal anti-inflammatory

drugs) should reduce the degree of renal dysfunction in

the perioperative period.

171

Of note, patients with DM

are at even higher risk for AKI compared with those

without DM, even among those with normal eGFR prior

to nephrectomy.

128

With significant nephron mass loss, hyperfiltration can

occur resulting in glomerular damage, exacerbation of

proteinuria and progressive sclerosis with further

decline in GFR.

Therefore, repeat assessment of blood

pressure, eGFR, and proteinuria should be performed

soon after nephrectomy then again in 3-6 months to

assess for development or progression of CKD. With

any compromise in eGFR or presence of CKD

complications, additional regular monitoring of kidney

function should be performed and further management

of CKD would be recommended with referral to

nephrology. Careful management of DM and HTN and

avoidance of substantial weight gain may slow or

prevent CKD progression and should be prioritized on a

long-term basis.

120,121,144,145,174-176

9. Clinicians should recommend genetic

counseling for any of the following: all

patients ≤ 46 years of age with renal

malignancy, those with multifocal or bilateral

renal masses, or whenever 1) the personal or

family history suggests a familial renal

neoplastic syndrome; 2) there is a first-or

second-degree relative with a history of renal

malignancy or a known clinical or genetic

diagnosis of a familial renal neoplastic

syndrome (even if kidney cancer has not been

observed); or 3) the patient’s pathology

demonstrates histologic findings suggestive of

such a syndrome. (Expert Opinion)

Recognition of familial forms of RCC can be of great

benefit to patients and their families. Genetic

counseling is typically pursued after biopsy or surgery

has been performed and pathology is available to guide

future testing. If positive, other manifestations of the

various syndromes can be identified and family

members can also be considered for genetic testing.

Proactive management of RCC and other familial

manifestations may considerably lessen the morbidity

and mortality associated with these syndromes.

Improved understanding of specific hereditary forms of

RCC has resulted in well-defined recommendations

regarding the role of AS, appropriateness of nephron-

sparing surgery, and timing of intervention for the

various syndromes.

19,177

For example, patients with VHL

rarely experience a metastasis when their tumors are

less than 3 cm, and are thus typically observed until

the largest tumor crosses this size threshold.

This is in

contrast to patients with HLRCC who usually present

with aggressive cancers that should trigger prompt

aggressive intervention.

178

While it is estimated that 4-6% of patients with RCC

may have a familial syndrome, some studies suggest

that contributing genetic mutations may be even more

common than previously appreciated, and referral for

genetic counseling should be considered more often

than in the past.

179

A positive family history (first-or

American Urological Association (AUA)

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second-degree relative with a history of renal

malignancy or a known clinical or genetic diagnosis of a

familial renal neoplastic syndrome, even if kidney

cancer has not been observed) should prompt referal

for genetic counseling. Identification of classic

manifestations of known familial syndromes is also a

strong indication for genetic evaluation.

180-182

Several

RCC syndromes have been characterized and are listed

in Table 5 along with their clinical correlates:

Patients presenting with bilateral or multifocal RCC

should also be considered for genetic counseling, as

should those with uncommon but characteristic tumor

histologies such as hybrid oncocytic/chromophobe

tumors suggestive of BHD. Other pathologic findings

that should prompt consideration for genetic counseling

include histology suggesting HLRCC/fumarate hydratase

deficiency or SDH deficient RCC, or AML in the presence

of one or more additional TS complex criteria.

180-182

Since sporadic RCC typically presents at a more

advanced age than hereditary RCC, patients presenting

at a young age should also be considered for genetic

evaluation. One important study of the SEER cohort

revealed that the median age of onset of sporadic RCC

was 64 years compared to 37 for those with hereditary

disease.

182

Based on this data, it was recommended

that patients diagnosed at the age of 46 years or

younger should be strongly considered for genetic

counseling.

Renal Mass Biopsy (RMB)

10. When considering the utility of RMB, patients

should be counseled regarding rationale,

positive and negative predictive values,

potential risks and non-diagnostic rates of

RMB. (Moderate Recommendation; Evidence

Level: Grade C)

RMB is an important diagnostic adjunct for selected

patients with renal masses suspicious for clinically

localized renal cancer. Patients seeking additional

information regarding their diagnosis or clinicians

needing more information may elect RMB for histologic

data to enhance counseling and clinical decision

making. Before undergoing RMB, consultation regarding

the performance characteristics and risks of RMB should

be undertaken. First, patients should understand that

RMB is generally a safe diagnostic test. The risk of

complications is low with the most common being renal

hematoma (4.9%), clinically significant pain (1.2%),

gross hematuria (1.0%), pneumothorax (0.6%) and

hemorrhage requiring transfusion (0.4%).

183-190,200

While the risk of post-procedure hemorrhage is small,

these risks may be amplified by aspirin, NSAIA, second

or third generation antiplatelet agents (i.e.

dipyridamole, clopidogrel), vitamin K/factor X inhibitors

(i.e. warfarin, apixaban), and low molecular weight

heparin (i.e. enoxaprin). Temporary discontinuation of

these agents is advised if the risk/benefit ratio allows.

American Urological Association (AUA)

Renal Mass and

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Table 5. Familial RCC Syndromes.

*Renal cancers associated with these syndromes are typically or often more aggressive

Syndrome Gene Clinical Manifestations

Von Hippel-Lindau (VHL) VHL Clear cell RCC, renal cysts, hemangioblastomas of the central

nervous system, retinal angiomas, pheochromocytoma

Hereditary Papillary Renal Car-

cinoma (HPRC)

MET Type 1 papillary RCC

Birt Hogg-Dubé (BHD) FLCN Chromphobe RCC, oncocytoma, hybrid oncocytic/

chromophobe tumors (HOCTs), clear cell RCC (less common),

renal cysts, cutaneous fibrofolliculomas, lung cysts, spontane-

ous pneumothorax

Hereditary Leiomyomatosis

and RCC (HLRCC)*

FH Type 2 papillary or collecting duct RCC, cutaneous leioyomyo-

mas, uterine leiyomyomas

Succinate Dehydrogenase Kid-

ney Cancer (SDH-RCC)*

SDHB/C/D Clear cell RCC, chromophobe RCC, type 2 papillary RCC, on-

cocytoma , pheochromocytoma/paraganglioma

BAP-1 Tumor Predisposition

Syndrome*

BAP-1 Clear cell RCC, uveal melanoma

Tuberous Sclerosis Complex

(TSC)

TSC1/2 AML, clear cell RCC, oncocytoma, lymphangioleiyomyomasto-

sis (LAM), seizures, developmental delay

Cowden/PTEN Syndrome Asso-

ciated RCC (CS-RCC)

PTEN Thyroid, breast, and endometrial cancers, mucocutaneous

lesions, RCC with papillary most common, also other forms of

RCC, including clear cell

Importantly, there are no reported cases of RCC tumor

seeding in the contemporary literature with modern

biopsy techniques, which typically utilize a coaxial

sheath. In addition, patients should be informed that a

RMB diagnostic of malignancy and histologic subtype

tends to be highly accurate.

Based on a bivariate meta-analysis of seven

studies that compared diagnosis using RMB with

surgical pathology, the sensitivity (96.7% (95%

CI 93.8-98.2%)), specificity (94.4% (95% CI

71.9–99.1%)), and positive predictive value

(98.8% (95% CI 97.0–99.5)) of core RMB are

excellent and a diagnosis of malignancy can be

trusted with certainty (Figure 2). I n addition,

histologic determination of RCC subtype is highly

accurate.

200,201

However, patients should be informed

that the non-diagnostic rate of RMB is approximately

14%, which can be substantially reduced with repeat

biopsy.

185-191,201

Another concern with RMB has been

histologic heterogeneity, particularly for benign tumors

such as oncocytomas. In these cases there may be a

concurrent focus of cancer (i.e. hybrid oncocytic tumors

with chromophobe RCC), which could lead to misleading

RMB results.

192

However, recent studies suggest that

this does not substantially alter the outcomes for most

such patients.

Pooled estimates of sensitivity and specificity and their

95% confidence intervals were modelled using the

metandi module in StataMP v14. Metandi performs

bivariate meta-analyses of sensitivity and specificity

using a hierarchical modeling approach.

On the other hand, RMB carries a concerning negative

predictive value (NPV 80.8%, 95% CI 70.1-88.3%),

suggesting that a non-malignant biopsy result may not

truly indicate that a benign entity is present. In the

systematic review performed by Patel et al., the NPV

was 63% indicating that among patients undergoing

extirpation despite a negative biopsy, 37% had

malignant disease on final surgical pathology.

200

As this

comprised a select population with high risk clinical and

imaging features, it likely represents the upper limit of

NPV for RMB. In addition, the accuracy of tumor grade

diagnosis with RMB is highly variable, ranging from 52-

76% in the literature. Sixteen percent (16%) of tumors

were upgraded from low-grade to high-grade at

surgical pathology. This is particularly pertinent for

patients with small renal masses, where 80-90% of

tumors are low-grade and the detection of high-grade

tumors is of paramount importance. Hence, this

represents a significant limitation of RMB.

185-190

Furthermore, oncocytic neoplasms may present a

challenge for RMB (i.e., differentiating chromophobe

RCC vs. oncocytoma). A summary of recommended

issues for emphasis during counseling about RMB is

listed below.

192,193

DISCUSSION POINTS FOR RMB:

 RMB is generally safe with low risk of significant

complications (bleeding) and no reported cases of

tumor seeding using contemporary techniques.

 A diagnosis of malignancy or RCC on RMB is highly

reliable.

 Potential limitations of RMB include:

 A benign biopsy must be distinguished from a non-

diagnostic biopsy (renal parenchyma or connective

tissues) result.

 A benign biopsy may not always correlate with

benign histology.

 Grade concordance from biopsy to surgically

resected tissue is imperfect.

 Oncocytic neoplasms may represent a diagnostic

dilemma.

 Biopsy or aspiration of cystic renal masses is

generally not advised due to concerns regarding

tumor spillage and a high likelihood of obtaining a

non-informative result due to sampling error.

11. Clinicians should consider RMB when a mass is

suspected to be hematologic, metastatic,

inflammatory, or infectious. (Clinical

Principle)

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

Figure 2. Reported sensitivity and specificity for a malignant diagnosis using core RMB when com-

pared with surgical pathology.

Pooled sensitivity: 96.67%; 95%CI, 93.79-98.24%; Pooled specificity: 94.45%; 95%CI, 71.93-99.13%

Patients presenting with an enhancing renal mass

should be considered for RMB if: 1) there is suspicion

that the lesion represents metastatic cancer from

another primary source; 2) the radiographic or clinical

picture suggests hematologic malignancy involving the

kidney; or 3) there is concern for an inflammatory or

infectious process. Although metastatic cancer involving

the kidney is frequently found at autopsy, clinical

presentation of renal metastases is uncommon. The

most common hematologic malignancy to involve the

kidney is lymphoma and the most common solid tumor

metastasis is lung cancer, although melanoma, colon

cancer and thyroid cancer have also been reported.

194

In patients with a prior history of malignancy with

potential renal metastasis, or in those with an atypical

renal mass and concerning constitutional symptoms,

RMB should be considered.

195

If metastatic cancer is

confirmed, systemic treatment is typically prioritized.

194

Metastases to the kidney are often multifocal, poorly

enhancing, and infiltrative rather than well demarcated,

although there are exceptions to these rules. Renal

lymphoma should be considered in patients with

infiltrative renal lesions, in those with lymphadenopathy

that is out of proportion to the renal primary, or when

the anatomic distribution of involved nodes is markedly

atypical for RCC. In contrast, patients with a solitary,

avidly enhancing renal mass and a remote history of

cancer will likely have RCC and can be managed

accordingly.

In patients presenting with signs and symptoms

consistent with an infectious or inflammatory condition

or those with a prior history of recurrent infections or

autoimmune disease, the clinician’s index of suspicion

for a non-neoplastic process, such as renal sarcoidosis,

abscess, or focal pyelonephritis, should be increased. In

this setting, RMB should be considered for diagnostic

purposes and to direct therapy.

196-199

12. In the setting of a solid renal mass, RMB

should be obtained on a utility-based

approach whenever it may influence

management. RMB is not required for 1)

young or healthy patients who are unwilling to

accept the uncertainties associated with RMB;

or 2) older or frail patients who will be

managed conservatively independent of RMB

findings. (Expert Opinion)

Patients with a renal mass should be counseled about

the differential diagnosis including the likelihood of

malignant versus benign histology. A utility-based

approach is recommended for RMB, which is not

indicated when it is unlikely to alter management

recommendations or patient choice.

200,201

Patients with

severe CKD often have benign or indolent tumors and

their management can be complex, and this represents

one of the cohorts that should be strongly considered

for RMB.

202

RMB should also be considered in patients

for whom it is difficult to decide between management

with PN versus RN, where additional oncologic risk

stratification may be helpful. Many young or healthy

patients are unwilling to accept the potential

uncertainty of RMB such as the possibility of a non-

diagnostic or false negative result, and will elect

intervention regardless of RMB outcome.

Some older

or frail patients are not healthy enough to undergo

intervention and will be managed conservatively even if

RMB suggests malignancy.

75,80,200,201

In these settings,

RMB is typically not required because it will not

materially alter counseling or management. Please refer

to guideline statements 10 and 13, which include

pertinent details regarding the processes, risks and

performance characteristics of RMB and further

considerations for patient counseling.

13. For patients with a solid renal mass who elect

RMB, multiple core biopsies should be

performed and are preferred over fine needle

aspiration (FNA). (Moderate

Recommendation; Evidence Level: Grade C)

RMB may be performed under CT or US guidance, with

at least 2-3 cores being obtained with a 16-18 gauge

needle to optimize diagnostic yield. FNA is associated

with a decreased diagnostic yield and core biopsy is

preferred when feasible. The Patel et al. systematic

review of RMB demonstrated core biopsy to have a

sensitivity of 97.5% while the sensitivity of FNA was

reported at 62.5%.

193

The diagnostic rate of RMB is

dependent upon obtaining viable tissue from the lesion

in question. The American Society of Cytopathology

endorses Rapid On-Site Evaluation (ROSE), which can

optimize specimen quality for pathologic evaluation by

obtaining real-time assessment of FNA or touch

imprints of core biopsies to confirm specimen

adequacy.

203

However, the additional challenges for

workflow and personnel issues to implement ROSE are

also recognized and such techniques are important but

not currently considered mandatory.

MANAGEMENT

Partial Nephrectomy (PN) and Nephron-Sparing

Approaches

14. Clinicians should prioritize PN for the

management of the cT1a renal mass when

intervention is indicated. In this setting, PN

minimizes the risk of CKD or CKD progression

and is associated with favorable oncologic

outcomes, including excellent local control.

(Moderate Recommendation; Evidence Level:

Grade B)

PN is a definitive surgical procedure that is associated

with excellent oncological and renal functional

outcomes, particularly in patients with small renal

masses. It also yields complete pathological information

regarding the excised tumor and minimizes the

oncological uncertainty that can occasionally be

associated with repeat sessions of TA. PN is associated

with urologic complications in a small proportion of

patients but most can be successfully managed with

conservative measures.

204

The EORTC randomized trial suggests that PN is

associated with similar oncological outcomes when

compared to RN for clinically localized small (<5cm)

renal masses, and the AHRQ systematic review and

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

update has reaffirmed this for carefully selected

patients.

204,205

Meta-analysis of the existing data further

documents that PN is associated with less decline in

postoperative GFR and a lower incidence of CKD stage

3 or above when compared to RN (figures 3 and 4).

PN is also associated with more favorable local

recurrence-free survival when compared to a single

session of TA (Figure 5). While patients undergoing PN

have a higher risk of blood transfusion and urological

complications, the overall complication rates

experienced by patients undergoing PN are similar to

other treatment modalities and can be minimized in

experienced hands. Given uncertainties regarding

future development of CKD, the increasing prevalence

of CKD risk factors (obesity, hypertension, tobacco use)

related to RCC in the general population, the risk of

recurrent or de novo disease in the contralateral renal

unit,

206

and the indolent nature of most small kidney

tumors, PN should be prioritized in the management of

patients with clinical T1a renal mass.

176,207-212

15. Clinicians should prioritize nephron-sparing

approaches for patients with solid or Bosniak

3/4 complex cystic renal masses and an

anatomic or functionally solitary kidney,

bilateral tumors, known familial RCC,

preexisting CKD, or proteinuria. (Moderate

Recommendation; Evidence Level: Grade C)

Absolute indications for PN included situations in which

RN would render the patient anephric or at high risk for

renal replacement therapy. These include patients with

an anatomic or functionally solitary kidney, bilateral

tumors, or known familial RCC. While most patients

with familial RCC have two functional renal units, they

are very likely to experience bilateral tumors, tumor

recurrence and require multiple renal surgeries

throughout their lifetime.

The importance of nephron

sparing approaches and thresholds for intervention (i.e.

3 cm) for most RCC syndromes have been well

established through the experience at the National

Cancer Institute.

213

PN in patients with absolute

indications should focus on preservation of renal

parenchymal volume and functional nephrons with

margin width being a less relevant consideration.

214

Approximately 25-30% of a well-functioning, solitary

kidney is generally sufficient to avoid renal replacement

therapy and therefore, overall preservation of renal

function is achievable in most patients with absolute

indications for PN.

215,216

All patients with an absolute

indication for PN should be advised about the potential

need for temporary or permanent renal replacement

therapy following surgery. In one series of solitary

kidneys managed with PN, rates of temporary and

permanent end-stage renal failure were 3.5% and

4.5% respectively.

217

Another study of solitary kidneys

reported acute renal failure in 12.7% of patients, and

proteinuria and significant CKD in 15.9% and 12.7% of

patients, respectively.

218

Traditional relative indications for PN have included

patients with conditions that would threaten future

function of a contralateral renal unit such as preexisting

CKD and proteinuria. In the 2016 AHRQ report of

patients with normal contralateral kidneys, rates of end

-stage renal disease (ESRD) for RN, PN, and TA were 1-

3%, 0.4-1%, and 1-2%, respectively.

However, the

current literature suggests that patients with pre-

existing CKD and proteinuria are at highest risk for

progressive CKD and ESRD.

219-221

It is noteworthy that

patients with proteinuria, even without a decrease in

GFR, are at increased risk of progressive loss of renal

function.

222

Therefore, PN should also be prioritized in

these patients.

16. Nephron-sparing approaches should be

considered for patients with solid or Bosniak

3/4 complex cystic renal masses who are

young, have multifocal masses, or

comorbidities that are likely to impact renal

function in the future, including but not

limited to moderate to severe hypertension,

diabetes mellitus, recurrent urolithiasis, or

morbid obesity. (Moderate Recommendation;

Evidence Level: Grade C)

The EORTC 30904 randomized trial of RN versus PN

demonstrated higher eGFR in patients undergoing PN

compared to RN: 66.8 versus 52.7 mL/min/1.73m

within the first year, respectively. However, there was

no evidence of subsequent decline in eGFR in either

surgical cohort and the rates of end stage renal disease

(eGFR less than 15 mL/min/1.73m

) were 1.5% and

1.6% respectively.

223

However, this was a population of

aged adults (median age >60 years old) in generally

good health with normal contralateral kidneys

(preoperative serum creatinine <1.25 mg/dL in >90%)

and thus should not be extrapolated to all patients with

clinically localized renal masses. Younger patients who

have longer life expectancy are theoretically at risk of

recurrent and/or contralateral disease as well as

competing health risks that can impact renal function

over their extended remaining life time. For this reason,

these patients should undergo nephron-sparing

approaches whenever technically feasible. In

reasonably healthy patients managed by experienced

surgeons, the risks of nephron sparing surgery are low

and balance the uncertainties of recurrent disease or

the development of unforeseen health issues. Patients

with multifocal tumors often have familial RCC and

should be managed as such.

They will typically

require multiple renal interventions throughout their

lifetime.

For these patients, the importance of

nephron sparing approaches and thresholds for

intervention have been well established through the

experience of the National Cancer Institute.

213

Lastly,

patients with significant risk for future CKD such as

patients with severe hypertension, diabetes mellitus,

strong stone diathesis, or morbid obesity should be

considered for nephron-sparing approaches in order to

optimize their renal function.

224-226

The risks of CKD

should be discussed with patients keeping in mind that

oncologic outcomes should remain a priority.

17. In patients who elect PN, clinicians should

prioritize preservation of renal function by

optimizing nephron mass preservation and

avoiding prolonged warm ischemia. (Expert

Opinion)

One of the main objectives of PN is to preserve renal

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

Figure 3. Mean change in eGFR for RN versus PN.

Figure 4. Meta-analysis of the incidence of stage 3 CKD with RN versus PN.

Figure 5. Meta-analysis of local recurrence rates for PN versus primary TA among studies with follow-up

of 48 months ± 12 months.

Abbreviations: CI, confidence interval; IV, inverse variance; PN, partial nephrectomy; TA, thermal ablation.

Note: Total patients is defined as all patients with biopsy proven RCC treated with each modality. Events refer

to number of patients with local recurrence.

with a solitary kidney, bilateral or multifocal disease, or

preexisting CKD or proteinuria.

214,227-229

However, even

when PN is performed electively, there may be value in

optimizing renal function on a long-term basis. Current

studies regarding the impact of incremental changes in

renal function related to renal cancer surgery on overall

survival do not extend beyond 10 years follow-

up,

165,219,220

but both the randomized trial of PN versus

RN and a plethora of comparative, retrospective data

indicate worse overall GFR and higher rates of CKD

stage ≥3 in patients undergoing RN.

65,223

In addition,

uncertainties regarding development of CKD in patients

without risk factors and the low, but tangible risk of

developing contralateral masses are reasons to consider

PN and other nephron sparing approaches when

technically feasible and have high likelihood of

success.

206

The recent literature demonstrates that the main

determinant of functional outcomes after PN is nephron

mass preservation, or the quantity of vascularized

parenchyma that is preserved by the procedure.

227-231

Efforts to optimize this parameter during tumor excision

and reconstruction should be prioritized, as long as

oncologic outcomes are not compromised.

232

Beyond this, prolonged warm ischemia should be

avoided, as it can lead to irreversible loss of function.

The exact threshold of warm ischemia at which

irreversible damage begins to occur is not well defined,

although some studies suggest that some patients may

begin to experience this to a significant degree at

approximately 25-30 minutes.

227-229

In general,

recovery from hypothermia is more consistent and

reliable with intervals up to 60-90 minutes being well

tolerated.

233

Nevertheless, even with hypothermia it is

best to avoid truly prolonged durations of ischemia, as

they can lead to increased risk of acute kidney injury,

which may complicate postoperative care.

231,234,235

Avoidance of ischemia or segmental clamping are other

strategies that have been advocated in an effort to

obviate ischemia injury.

227,236-238

Such approaches can

be supported as long as nephron mass preservation

remains strong and perioperative and oncologic

outcomes are not compromised.

239,240

18. For patients undergoing PN, clinicians should

prioritize negative surgical margins. The

extent of normal parenchyma removed should

be determined by surgeon discretion taking

into account the clinical situation and tumor

characteristics, including growth pattern, and

interface with normal tissue. Tumor

enucleation should be considered in patients

with familial RCC, multifocal disease, or

severe CKD to optimize parenchymal mass

preservation. (Expert Opinion)

The primary goal of PN is complete tumor excision and

as such achieving negative surgical margins should

remain a priority. Positive surgical margins introduce

oncological uncertainty and cause patient anxiety.

Recent studies have suggested inferior oncological

outcomes in patients with positive surgical margins

after PN.

241,242

Preservation of renal parenchyma is among the

strongest predictors of functional outcomes after PN

and is thus particularly important in patients with

severe CKD or a propensity for multifocal and bilateral

RCC.

221

The amount of normal tissue excised during PN

should be determined by surgeon judgment taking into

account patient and tumor characteristics. The concept

of tumor enucleation (or blunt excision of a tumor with

minimal margin during nephron-sparing surgery)

originated in the familial RCC population as a technique

to preserve renal parenchyma in patients with multiple

tumors requiring several surgeries over a lifetime.

243

However, even for familial RCC patients tumor

enucleation should be applied selectively. For example,

some syndromes, such as here HLRCC, tend to have

unifocal aggressive tumors and are best managed with

wide margin PN or RN.

Enucleation has subsequently been evaluated in the

function, and this is particularly important in patients

sporadic RCC population with a number of studies

reporting similar oncological outcomes compared to

traditional PN, in which sharp excision is performed

with intentional removal of a modest rim of normal

adjacent parenchyma.

244-247

Most studies comparing

enucleation and traditional PN have been retrospective

and uniform pathologic review has not been applied.

Selection for enucleation based on favorable imaging

characteristics such as homogeneity and encapsulated

appearance is likely another contributing factor in many

of these studies.

248

In addition, tumor enucleation is

based on the concept of blunt dissection along a tumor

pseudocapsule, which is present in many but not all

renal cancers.

249-251

When present, the pseudocapsule

can contain invasive cancer in up to one third of cases

with an unclear influence on prognosis.

252

Given these

concerns, great care should be taken to assess tumor

growth pattern and its interface with the normal

parenchyma to assess feasibility for successful

enucleation. Until prospective evaluation is available for

sporadic renal tumors, enucleation is best utilized on a

selective basis.

Frozen section analysis of the margins during PN or

tumor enucleation can be considered on a selective

basis, particularly when there is concern about the

gross specimen. The management of positive surgical

margins after PN or tumor enucleation remains

controversial. A variety of factors should be taken into

account during counseling including the extent of the

margin (microscopic versus extensive), tumor histology

and grade, and other indicators of tumor biology such

as locally invasive phenotype. Most patients with

microscopic positive surgical margins associated with

small renal masses tend to do well with expectant

management, although close surveillance is

recommended.

253

Radical Nephrectomy (RN)

19. Clinicians should consider RN for patients with

a solid or Bosniak 3/4 complex cystic renal

mass whenever increased oncologic potential

is suggested by tumor size, RMB (if obtained),

and/or imaging. (Moderate Recommendation;

Evidence Level: Grade B) In this setting, RN is

preferred if all of the following criteria are

met: 1) high tumor complexity and PN would

be challenging even in experienced hands; 2)

no preexisting CKD or proteinuria; and 3)

normal contralateral kidney and new baseline

eGFR will likely be greater than 45 mL/

min/1.73m2 even if RN is performed. If all of

these criteria are not met, PN should be

considered unless there are overriding

concerns about the safety or oncologic

efficacy of PN. (Expert Opinion)

Many cT1b/T2 tumors can be considered for PN, and

observational studies suggest that acceptable outcomes

can be achieved with PN in this setting, assuming

appropriate patient selection and surgical experience.

254

-261

However, oncologic potential correlates with tumor

size as reflected by increased incidence of high grade

tumor, less favorable histology, and locally advanced

features.

150,262

Infiltrative appearance on imaging also

suggests high grade tumor and/or poorly differentiated

elements, including sarcomatoid features.

263,264

In this

setting PN may place the patient at increased risk of

local recurrence

265

and thus RN may provide an

oncologic advantage.

259,262

Another major consideration for some cT1b/T2 tumors

relates to feasibility of PN, particularly if tumor

complexity is increased related to hilar tumor location.

Urologic complications such as urine extravasation and

postoperative bleeding are more common after PN for

high complexity cases.

266,267

In this setting referral to a

more experienced colleague or center should be

considered to assess feasibility of PN. If PN appears to

be challenging even in experienced hands RN should be

considered, particularly if oncologic indicators are

unfavorable as discussed above.

259,262

The other important consideration for such patients is

functional, and recent studies suggest that there is a

subgroup of patients who experience relatively

favorable outcomes with RN, even if they develop CKD

after surgery.

165,219,220,223

Such patients have no

preexisting CKD (baseline GFR > 60mL/min/1.73m

no proteinuria (dipstick negative or trace), and a

normal contralateral kidney that is expected to provide

an eGFR of greater than 45 mL/min/1.73m

after RN.

Patients with CKD primarily due to surgery who meet

the above criteria appear to have overall survival and

stability of renal function during intermediate-term

follow-up (approximately 10 years) similar to those

without CKD even after surgery.

165,219,220

Results of

EORTC 30904 also supports good survival in select

patients managed with RN even if they develop CKD

after surgery. Overall survival in this study with over a

decade of follow-up was almost identical in the RN and

PN cohorts, even though the median new baseline GFR

in the RN cohort was 52 mL/min/1.73m

, confirming

that most RN patients had CKD after surgery.

A related consideration when deciding about the utility

of PN is the amount of parenchymal mass that will be

preserved with the procedure. Some large centrally

located tumors have already replaced a substantial

proportion of the kidney, and in this setting PN may

yield a remnant kidney with only marginal function

after excision and reconstruction have been

accomplished.

259

In general, median loss of global renal

function with PN is about 10%, while RN is typically

associated with about 35-40% median loss of global

function, although this can vary substantially for RN

based on uneven split renal function, and for PN based

on tumor complexity, as discussed above.

228

Patients who combine all of the salient features in

Statement 19 should be considered for RN as these are

patients for whom RN may provide an oncologic benefit

with very little downside, and in whom the oncologic

and perioperative risks of PN would be increased.

Beyond these circumstances, PN is generally preferred

for surgical excision. However, in some patients who do

not meet the composite profile in Statement 19, PN

may not be possible or advisable even in experienced

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

hands. In this setting RN may be required based on

surgeon discretion, with input from other services such

as nephrology when relevant.

259

The literature regarding the appropriate role for RN in

localized disease has evolved substantially yet still

remains controversial in many aspects.

259

Almost all

studies in this domain are retrospective and

observational, and definitive conclusions regarding

comparative efficacy of PN versus RN often cannot be

drawn.

65,204

The only prospective, randomized trial of PN

versus RN was in patients with clinically localized

tumors 5 cm or smaller and demonstrated equivalent

oncologic outcomes.

268

This trial also failed to

demonstrate an overall survival benefit for PN over RN,

and while it can be criticized for a number of flaws, this

is still provocative data suggesting that the survival

benefits of PN in an elective setting may not be as

substantial as previously thought.

212

A prospective trial

of RN versus PN in patients with increased oncologic

risk would address these controversies and would likely

prove very informative.

259

Until this is done, oncologic

and functional considerations and perioperative risks

must be carefully weighed during individualized patient

counseling.

269-271

In select patients RMB may be helpful

for risk stratification, and nuclear renal scan or

differential parenchymal volume analysis

272

to provide

split renal function can also be considered.

200

Surgical Principles

20. For patients who are undergoing surgical

excision of a renal mass with clinically

concerning regional lymphadenopathy,

clinicians should perform a lymph node

dissection including all clinically positive

nodes for staging purposes. (Expert Opinion)

If suspicious lymphadenopathy is identified on imaging

or during surgical exploration, a lymph node dissection

(LND) should be performed with removal of all clinically

evident nodes, if feasible, primarily for staging and

prognostic purposes.

273,274

In a prospective study by

Blom and colleagues, 772 patients with cT1-T3N0M0

RCC were randomized to RN plus LND versus RN

alone.

275

Fifty-one patients in the RN plus LND group

had palpable nodes and 10 (19.6%) were N+ on final

pathology. For patients in this cohort without palpable

nodes only 4/311 (1.3%) were pN+. Overall, only 4%

of patients in the RN plus LND cohort had pN+ disease.

Cancer-specific and overall survival rates were nearly

identical in the RN plus LND and RN alone cohorts. Data

from this study and others have contributed to strong

consensus that LND need not be performed routinely in

patients with localized kidney cancer and clinically

negative nodes.

273-275

Other investigators have studied risk factors for LN

involvement in patients undergoing nephrectomy and

have found that large primary tumor (>10 cm), clinical

stage T3/T4, high tumor grade (Fuhrman grade 3 or 4),

sarcomatoid features, and histologic tumor necrosis all

correlate with increased incidence of pN+ disease.

273

Patients with 2 or more of these risk factors were found

to be at substantially increased risk of nodal

involvement (>40%), and prospective evaluation has

confirmed these findings. Hence, selective performance

of LND should be considered at the time of renal cancer

surgery.

273

However, this is primarily for staging

purposes, as recent studies have been unable to

confirm a survival benefit for lymph node dissection

among patients undergoing RN for non-metastatic RCC.

276-279

If lymph node involvement is confirmed on final

pathology, adjuvant therapy and medical oncology

consultation should be considered (See Statement 24

for specific recommendations regarding this issue).

21. For patients who are undergoing surgical

excision of a renal mass, clinicians should

perform adrenalectomy if imaging and/or

intraoperative findings suggest metastasis or

direct invasion of the adrenal gland. (Clinical

Principle)

Adrenal involvement with RCC is a poor prognostic

finding and fortunately relatively uncommon outside of

the advanced disease setting.

274,280

In the more recent

revisions of the AJCC TNM classification scheme,

adrenal involvement with RCC was upstaged to pT4 if

due to contiguous involvement and pM+ otherwise,

reflecting likely hematogenous dissemination.

adrenal involvement is confirmed on final pathology,

adjuvant therapies and medical oncology consultation

should be considered (see statement 24).

Several studies have shown that occult adrenal

involvement is uncommon in patients with clinically

localized kidney cancer, and the adrenal gland can be

spared in this setting without compromising oncologic

outcomes.

274,281,282

Adrenalectomy should be performed

if preoperative imaging or intraoperative inspection

suggests metastasis or adrenal enlargement. In this

setting, adrenalectomy has important prognostic utility

and may occasionally have therapeutic potential.

274

The

one exception to this is when the patient has a well-

characterized non-functioning adenoma, which may not

mandate surgical excision.

If locally advanced features are identified

preoperatively or during exploration, adrenalectomy

should be considered if the gland is in close proximity

to tumor. However, the adrenal may be spared in this

setting if the contralateral adrenal gland is absent and

the ipsilateral gland demonstrates normal morphology

and no malignant involvement.

274

22. In patients undergoing surgical excision of a

renal mass, a minimally invasive approach

should be considered when it would not

compromise oncologic, functional, and

perioperative outcomes. (Expert Opinion)

Minimally invasive techniques have permeated surgical

practice with the hope of maintaining the oncological

efficacy of open surgery while reducing its morbidity.

Multiple studies demonstrate recuperative and cosmetic

advantages to minimally invasive RN in comparison to

open surgery.

283-285

Laparoscopic and robotic PN have

demonstrated equivalent surgical margin status and

oncological outcomes when compared to open surgery

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

in well-selected patients.

286-288

The high rate of

percutaneous TA, relative to surgically performed

ablation, may explain the favorable perioperative

outcome and harm profile associated with these

treatment options.

204

While minimally-invasive

approaches have also been reported in increasingly

complex indications (large renal masses, renal vein

thrombi and patients with solitary kidneys),

289-293

patient safety and adherence to prior guideline

statements regarding oncologic outcomes, indications

for nephron sparing surgery, and preservation of renal

function should be prioritized relative to the choice of

surgical access approach.

The current data suggest that the benefits of minimally

invasive surgery are realized in the short-term,

perioperative period and are equivalent to open surgery

with intermediate- and long-term follow-up.

294-296

The

limited quality-of-life data that exist in this realm fail to

demonstrate clinically significant differences in health

related quality of life among patients undergoing

laparoscopic and open nephrectomy.

297

While cost-

effectiveness remains unanswered due to limitations of

the data and considerations of long-term surveillance;

the potential increase in costs related to certain

minimally invasive approaches may be balanced with

shorter hospital stays and earlier convalescence.

298-302

Ultimately, the decision for management strategy—RN,

PN, or TA—should be made irrespective of approach

available and clinicians should employ minimally

invasive approaches only when oncological, functional,

and perioperative outcomes are unlikely to be

compromised.

Other Considerations

23. Pathologic evaluation of the adjacent renal

parenchyma should be performed and

recorded after PN or RN to assess for possible

intrinsic renal disease, particularly for

patients with CKD or risk factors for

developing CKD. (Clinical Principle)

Proper evaluation of the non-neoplastic kidney disease

is infrequently performed or reported

303

but is essential

to achieve optimal patient management. Given that

diabetes and hypertension are independent risk factors

for RCC, diabetic nephropathy and hypertensive

nephropathy are found in 8-20% and at least 14% of

tumor nephrectomies, respectively.

144-146

Recognizing

this general deficiency, the College of American

Pathologists established a requirement that pathologic

evaluation of the renal parenchyma for possible

nephrologic disease should be included in all synoptic

reports for kidney cancer.

304

Additional gains in clinical

outcomes may be achieved with improved identification

and management of non-neoplastic renal diseases. In

patients with more significant CKD, particularly those

with significant proteinuria, the urologist may elect to

submit additional specimens of normal parenchyma for

a formal pathologic medical renal evaluation which may

include adjunct testing. In these cases, the urologist

should communicate directly with the pathologist to

optimize testing and the additional information

obtained.

24. Clinicians should consider referral to medical

oncology whenever there is concern for

potential clinical metastasis or incompletely

resected disease (macroscopic positive margin

or gross residual disease). Patients with high-

risk or locally advanced, fully resected renal

cancers should be counselled about the risks/

benefits of adjuvant therapy and encouraged

to participate in adjuvant clinical trials,

facilitated by medical oncology consultation

when needed. (Clinical Principle)

Systemic therapies for metastatic RCC continue to

expand rapidly through the use of targeted therapies,

new generation immunotherapies, combination and

sequential therapies and a broad array of therapeutics

currently in clinical trials. Overall response rates, cancer

-specific and overall survival continue to improve, albeit

with associated toxicities.

305-307

Decisions regarding

when to begin systemic therapy and which therapies to

use in the first and second line are complex and

evolving quickly. Risk stratification using the IMDC and

MSKCC criteria guide initial therapeutic choices and

should be made in consultation with an experienced

medical oncologist.

181,308

Given the success of systemic therapies for metastatic

disease, the role of tyrosine kinase inhibitors and

immunotherapies have been and are being tested in the

adjuvant setting.

309

Multiple nomograms and algorithms

are available to predict recurrence risks and guide

eligibility for adjuvant kidney cancer trials.

310

Clinicians

may access these tools as on-line calculators for point

of care patient counseling. Eligibility and radiographic

assessment for adjuvant clinical trials in kidney cancer

continue to be refined.

311

In 2017, the FDA approved

sunitinib malate as the only therapy for the adjuvant

treatment of adult patients at high risk of recurrent RCC

following resection based on a multicenter, double

blinded placebo controlled trial (S-TRAC) in 615

patients who were randomized to receive either 50mg

of sunitinib malate once daily for 4 weeks on then two

weeks off, or placebo.

312

The study met its primary

endpoint demonstrating an improvement in disease-

free survival; however, significant differences in overall

survival were not observed.

313

While the current standard of care for patients with

fully resected renal cancers remains close clinical and

radiographic observation, patients with a high risk of

recurrence should be counseled regarding systemic

adjuvant options and/or considered for enrollment into

adjuvant clinical trials, facilitated by medical oncology

consultation when needed.

Thermal Ablation (TA)

25. Clinicians should consider TA as an alternate

approach for the management of cT1a solid

renal masses <3 cm in size. For patients who

elect TA, a percutaneous technique is

preferred over a surgical approach whenever

feasible to minimize morbidity. (Moderate

Recommendation; Evidence Level: Grade C)

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

The literature regarding TA for localized renal masses

has further matured allowing for a more meaningful

assessment of oncologic outcomes. Follow-up in some

TA studies has now reached 5 years or more and

thereby facilitates a more robust comparison of TA with

surgical excision.

211,247

Results with TA are particularly

encouraging for smaller renal masses (<3 cm) making

it a reasonable alternate approach in this setting. The

recent AHRQ meta-analysis demonstrated comparable

metastasis-free survival for PN and TA

, and analysis

of population-based (SEER) and institutional studies

demonstrated median 5-year cancer-specific survival

rates of 100% (range 97-100%) and 94% (range 92-

97%) for PN and TA, respectively.

However, local recurrence-free survival is generally

reported as favoring surgical extirpation. In the recently

updated AHRQ meta-analysis of studies comparing PN

and TA, the risk ratio for local recurrence was 0.55

(95% CI: 0.33-0.91) in favor of PN (Figure 5, see

Statement 14).

Median local recurrence-free survival

across the studies was 99.5% for PN and 93.9% for TA.

Since the morbidity of repeat ablation, particularly

percutaneous treatment, is generally low, local

recurrences may often be salvaged with repeat TA.

When considering such salvage attempts in addition to

the initial ablation, the AHRQ meta-analysis reported no

statistical difference in the risk ratio for local recurrence

comparing PN and TA (RR 0.97; 95% CI: 0.47-2.00,

Figure 6).

It should be noted; however, that this

analysis was limited by inclusion of only three TA

studies,

314-316

one of which did not report any

recurrences in either group

316

making precise estimates

of recurrence risk impossible. Experience with TA of

cystic renal tumors is limited given concerns for

possible tumor seeding and inhomogeneous distribution

of thermal energy. It is the Panel’s opinion that routine

consideration of TA for cystic lesions requires further

investigation.

Single institution TA studies have optimized therapeutic

efficacy by improving patient selection. Most studies

suggest that increasing tumor diameter is the key

predictive factor, as it has been associated with greater

likelihood of incomplete ablation and local recurrence.

For cryoablation, Tanagho et al.

317

reported that tumor

size > 2.5 cm was the sole factor predictive of local

recurrence on multivariate analysis. Using RFA, Gervais

and colleagues

318

reported 100% effectiveness for

tumors < 3 cm and 81% for tumors larger than 3 cm.

Similarly, Best et al.

319

demonstrated 5-year overall

disease-free survival of 95% for RFA of tumors < 3.0

cm compared to 79% for tumors larger than 3.0 cm.

Although some institutional series advocate TA for

larger tumors, it has been acknowledged that the risk

of complications, in particular renal tumor fracture and

hemorrhage, is higher when treating tumors greater

than 3 cm.

320-322

Thus the panel felt that TA should

optimally be reserved for smaller tumors less than 3 cm

in size unless patient co-morbidities or other factors

dictate otherwise.

Preservation of renal function after treatment is an

important goal in the management of smaller renal

masses, particularly in patients with pre-existent CKD.

As with PN, TA minimizes parenchymal loss and

improves long-term renal function compared to RN. The

AHRQ meta-analysis demonstrated that patients

undergoing TA have similar renal functional outcomes

to those undergoing PN.

TA also has a favorable

morbidity profile in comparison to extirpative surgery.

Transfusion rates, length of hospital stay, and

conversion to RN all favor TA over PN.

Minor and

major Clavien complication rates do not differ

significantly between TA and PN.

Both percutaneous and laparoscopic approaches to TA

have similar efficacy.

323-326

However, the percutaneous

approach is associated with shorter procedure time,

quicker recovery, and lower narcotic requirements and

should be the preferred approach to TA. For instance,

Bandi and colleagues reported that percutaneous

cryoablation was associated with significantly reduced

anesthesia time (148 versus 247 minutes), shorter

mean hospital stay (1.1 versus 2.5 days), and shorter

time to complete recovery (13.5 versus 27.5 days)

when compared to laparoscopic cryoablation.

327

Many of

these considerations translate to an economic

advantage for the percutaneous approach. Hinshaw and

colleagues demonstrated 40% lower hospital charges

for percutaneous cryoablation compared to laparoscopic

cryoablation, and Castle et al. reported that total costs

for percutaneous RFA were over 50% lower than for

laparoscopic RFA.

301,323

Tumor location and complexity also play an important

role in selection for TA. Completely intrarenal lesions or

those immediately adjacent to the sinus or hilum are

more difficult to treat effectively by TA. Percutaneous

displacement techniques such as the use of fluid (hydro

-dissection), carbon dioxide, or spacer balloons

frequently enable separation of adjacent structures

from the anticipated zone of ablation, rendering many

cases suitable for percutaneous TA. A laparoscopic

approach is seldom needed except for occasional cases

in which adhesions prevent displacement of adjacent

structures or when the collecting system is at risk for

serious injury even with thermo-protective maneuvers

such as pyeloperfusion.

326

In such cases, laparoscopic

TA or PN can be considered.

26. Both radiofrequency ablation (RFA) and

cryoablation may be offered as options for

patients who elect TA. (Conditional

Recommendation; Evidence Level: Grade C)

There are no randomized studies directly comparing

cryoablation to RFA. Current retrospective comparisons

are limited by variability in patient selection, tumor size

and location, technique, and laparoscopic or

percutaneous approach. Two large single institution

studies with significant experience with both

cryoablation and RFA have reported comparable

oncologic outcomes (local recurrence-free survival and

cancer-specific survival), impact on renal function, and

complication rates for the two modalities.

328,329

Two

meta-analyses of the literature have confirmed no

significant differences between cryoablation and RFA in

treatment outcomes as defined by complications,

metastatic progression, or cancer-specific

survival.

75,85,330

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

Optimal TA requires an understanding of the

mechanism of action for each technique and

appropriate ablation monitoring. RFA utilizes high

frequency alternating current (460-500 kHz) to induce

ion agitation and frictional heating in adjacent

tissue.

331,332

This can be achieved through two types of

radiofrequency generator systems: a temperature-

based system, which drives the current to reach a

target temperature, or impedance-based systems,

which continue ablation until a predetermined

impedance level is reached.

16,331,332

RFA systems utilize

either single or multi-tined electrodes, which are

designed to optimize tissue volume ablation.

331,332

Impedance-based systems apply algorithmic gradual

increases in electrical current while monitoring for rapid

impedance changes that indicate tissue charring near

the electrode. Meta-analysis has demonstrated

reproducible outcomes for ablation of renal masses and

no superiority of either temperature or impedance-

based RFA.

333

Cryoablation systems leverage the Joule Thompson

effect to generate lethal temperatures below -20 to -40

°C, resulting in coagulative tissue necrosis.

332,334,335

The

volume of lethal temperature generated during

cryoablation is regulated by the duration of freezing,

number of freeze cycles, size and number of

cryoprobes, and local tissue interactions.

332,334-337

Woolley et al. showed in a dog model that larger

volumes of renal tissue necrosis result from a double

freeze compared to a single freeze. They found no

difference in volumes of necrosis between active and

passive thawing between the freezing cycles. However,

active thawing saves time.

336

Thus, a commonly used

protocol for renal tumor ablation is termed “10-8-10”,

and consists of two 10 minute freezing cycles separated

by an 8 minute active thawing cycle. Monitoring the

progress of cryoablation is done through real time

imaging of the iceball. Complete treatment of a tumor

requires that the iceball extend beyond the tumor

because the peripheral leading edge of the iceball is at

sub-lethal temperatures, and the iceball thus provides

an overestimate of the zone of ablation.

334,335

Lethal

temperatures are reached approximately 5 mm from

the periphery of the iceball.

332,334,335

RFA and cryoablation differ in how to ensure complete

coverage for larger or irregular tumors. For small

tumors optimally shaped for a given electrode type, a

single RFA application may be sufficient to create a

zone of ablation that covers the tumor. For irregularly

shaped tumors, larger tumors, and/or tumors where

the electrode is not optimally centered in the tumor,

multiple overlapping ablations may be required with

electrode repositioning between ablations to adequately

treat the entire tumor. In contrast to RFA, where

sequential overlapping ablations may be required,

cryoablation allows simultaneous activation of multiple

cryoprobes in the synergistic creation of an iceball that

is larger than the simple additive effect of each

cryoprobe.

334,335,337

Thus, treatment planning involves

choosing the correct number and size of cryoprobes as

well as their relative distribution within a renal tumor in

order to create a zone of lethal ice that covers the

entire tumor.

27. A RMB should be performed prior to

(preferred) or at the time of ablation to

provide pathologic diagnosis and guide

subsequent surveillance. (Expert Opinion)

Although solid, enhancing renal masses are most often

RCC, the differential diagnosis also includes benign

tumors, such as oncocytoma and AML, non-RCC

malignancies, and metastatic lesions. TA by its nature

will lead to tissue necrosis and therefore will not allow

clinicians to acquire diagnostic tissue after ablation has

been performed. A diagnostic RMB prior to TA is

therefore the only realistic opportunity to render a

diagnosis in patients who elect this management

strategy. Notwithstanding most patients’ desire to know

the histology of their tumor, failure to make such a

diagnosis could create significant challenges. These

include difficulty determining the intensity of

surveillance, which might be abbreviated or tailored for

patients who have a benign or indolent lesion.

338

addition, emerging evidence suggests that RCC subtype

may impact sensitivity to thermal injury and thereby

treatment success and recurrence risk.

339

Diagnosing a

metastatic lesion may significantly impact treatment or

surveillance for patients with other known

malignancies. Finally, should the patient develop a

recurrence after TA, particularly at a distant site,

knowledge of the primary tumor type could significantly

impact treatment decisions.

For all of these reasons, RMB prior to or concurrent with

TA is strongly advised. Performing RMB prior to TA as a

separate procedure may facilitate more rational

counseling and avoid treatment of benign tumors,

which may be particularly advantageous for patients in

whom the risk of TA may be increased due to

challenging tumor size and location, or for patients with

marginal renal function.

340,341

However, in many cases

RMB as a separate procedure can increase the risk and

cost associated with the TA management strategy.

Therefore, decisions about timing of RMB relative to TA

should be made on an individualized basis.

28. Counseling about TA should include

information regarding an increased likelihood

of tumor persistence or local recurrence after

primary TA relative to surgical excision, which

may be addressed with repeat ablation if

further intervention is elected. (Strong

Recommendation; Evidence Level: Grade B)

There are no prospective, randomized trials that

directly compare local recurrence-free survival (LRFS)

after TA to either RN or PN. The AHRQ meta-analysis

identified 14 retrospective studies (3,916 total patients)

that compared LRFS between TA and PN, while only two

studies (217 patients) compared TA to RN. The formal

analysis was updated and prioritized the limited number

of TA studies with longer follow-up (48 ± 12) to provide

a more meaningful comparison. Local recurrence was

significantly less common with PN when compared to

TA when only the primary ablation was considered (RR

0.55, 95% CI 0.33-091; Figure 5).

This corresponded

to local control rates for primary TA in the range of 85-

95% (interquartile range) compared to 97-100% for PN

across studies (Figure 5, see Statement 14). Patients

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

should be informed of these differences during

counseling about the relative merits and limitations of

TA. However, when the meta-analysis allowed for a

salvage or secondary ablation, no difference in local

control was noted (RR 0.97, 95% CI 0.47-2.00)(Figure

6).

A small minority of patients with local recurrence

after TA are not candidates for salvage TA due to tumor

progression and may require surgical salvage. In this

setting, post-ablation fibrosis may present substantial

challenges, and a minimally invasive approach may not

be feasible. However, PN is typically achievable even in

this salvage setting, although experience with this

scenario can be of considerable value.

342,343

There was

insufficient evidence to compare LRFS rates for TA

versus surgical extirpation based on the type of

ablation (RFA or cryoablation) or approach to ablation

(laparoscopic or percutaneous).

Active Surveillance (AS)

The decision to embark on a course of AS or expectant

management rather than treatment in the setting of a

localized renal mass presumed to be a renal cancer

requires thoughtful consideration by both the patient

and the physician. In making the decision, an objective

baseline evaluation of patient, tumor, and treatment-

related factors should be undertaken (Figure 7). This

should include formal decision-making tools whenever

possible leading to a well communicated risk-benefit

analysis unique to the individual patient’s

circumstances.

110,344-347

The shared decision-making

process should be consistent with the patient’s inherent

preferences and tolerance of uncertainty.

348

High level data regarding the optimal frequency and

preferred imaging modalities for renal mass

surveillance are lacking. Therefore, at the time of the

initial baseline assessment and during subsequent re-

assessments, the clinician should estimate how to best

achieve the goals of (1) preventing stage progression,

(2) maintaining renal function and (3) avoiding the

potential risks of treatment when it is unlikely to

provide an oncologic or survival benefit. At the onset of

AS, the clinician should request and evaluate prior

abdominal imaging that may demonstrate the existence

of the renal mass at an earlier time point to assess

growth rate or changes in clinical stage. Next, patients

placed on a program of non-intervention should be

considered for either AS or expectant management

(observation or watchful waiting) (Figure 7).

AS is most appropriate for patients in whom the

anticipated net benefit of AS is modest to significant

when compared to treatment. Excluded from this track

are patients who are reasonable candidates for

intervention if tumor size, infiltrative appearance,

interval growth, or RMB suggest the potential for cancer

progression, unless they are willing to accept the

associated increase in oncologic risk (see statement 31

and 32 below). Patients with no prior imaging should

have surveillance imaging initially every 3 to 6 months

to assess for interval growth, substantial radiographic

changes in the character of the lesion, or the presence

of rare occult synchronous metastases in the setting of

a small renal mass. The preferred modality is not well

established in the literature, but initial imaging should

preferably consist of contrast-enhanced cross-sectional

imaging. Subsequent imaging may include the same or

when appropriate an abdominal US can be substituted.

Abdominal US (as opposed to retroperitoneal US), may

have the additional benefit of a survey of the

intraabdominal organs for progression. Differences in

tumor dimension measurements between these

different modalities may be significant and should be

interpreted with caution when making treatment

decisions.

RMB can be considered for additional risk

stratification for patients with solid masses on AS. For

those with predominantly cystic lesions, RMB should be

avoided.

It is recognized that not all patients on AS will require

the same intensity of surveillance as their tumor

biology, risk calculations and tradeoffs, and personal

objectives may differ. Some patients may therefore

require more intensive AS while others require less

intensive AS. The decision as to the frequency and

imaging modality must therefore be customized and

informed by robust communication focusing on goals,

risks and triggers for intervention. RMB can be a helpful

adjunct to guide these clinical decisions (see statement

10). However, even when RMB suggests the tumor is

benign, the predictive value of a core biopsy is

imperfect due to tumor heterogeneity and the

possibility of collision tumors.

192,193

Currently there are

insufficient data to recommend that all patients with

benign RMBs can be advised that they no longer need

follow-up imaging. Judicious surveillance in appropriate

patients with benign appearing RMBs remains a prudent

strategy.

Expectant management (observation) is appropriate in

patients in whom treatment poses an unacceptably high

periprocedural or renal functional risk than surveillance.

In this setting, the use of abdominal US of the

retroperitoneal and intraperitoneal organs can be

performed more frequently than formal contrast based

cross-sectional imaging to screen for stage progression

which may trigger systemic or palliative therapy in the

appropriately selected patient.

Regardless of the intensity of surveillance, chest

imaging with plain radiography (CXR) is warranted

annually or if intervention triggers are encountered or

symptoms arise. The intensity of surveillance can be

attenuated if the renal mass exhibits slow growth

kinetics, is noted to be radiographically stable or if the

patient’s medical condition deteriorates. In cases such

as this, patients can cross over between AS and

expected management (observation) based on

changing risk profiles, performance status, absolute

tumor size, tumor growth kinetics, stage progression or

other recalibration triggers for possible

intervention.

349,350

While no level 1 data exist that

define these triggers precisely, they should generally be

based on changes in tumor-based risk (absolute size >

3cm, median growth rate in excess of 5mm/year, or

stage migration) or patient-based risks (co-morbidities)

with continual objective reassessments to include the

use of RMB when appropriate.

349,350

Published data

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

Figure 7. Algorithm for AS or expectant management of localized renal masses suspicious for

malignancy.

demonstrate that in most instances, judicious delayed

intervention for localized stage I renal masses remains

effective.

159,349-354

The key to successful AS of a localized renal mass

remains thoughtful and recurrent reassessments and

robust communication in partnership with the patient

and his/her caregivers. Prospective trials, ideally

randomized, of AS versus treatment, with improved

reporting and more extended follow-up, should be

prioritized to provide higher quality data about

oncologic, functional and survival outcomes.

29. For patients with a solid renal mass < 2cm, or

those that are complex but predominantly

cystic, clinicians may elect AS with potential

for delayed intervention for initial

management. (Conditional Recommendation;

Evidence Level: Grade C)

AS appears to be a safe and effective option for

selected patients who have been properly informed of

the risks and benefits of each management strategy. In

the published AS literature, in which patients were

primarily greater than 70 years old, tumor size

averaged approximately 2 cm, and follow-up ranged

from 12-36 months, cancer-specific and metastasis-free

survival rates were 98-100%.

349,350

When the oncologic

risks are particularly low and the pathology of the

lesion is uncertain, (e.g., tumors < 2 cm), AS with

potential delayed intervention is an acceptable option

for the initial management of all patients, not just those

with limited life expectancy or poor performance status.

More recent studies have demonstrated that complex

cystic masses, particularly Bosniak 3 category lesions

and those that are predominantly cystic, also often

have indolent tumor biology and favorable outcomes on

AS.

152-154

Repeat imaging in 3-6 months to assess for interval

growth or substantial radiographic changes in the

character of the lesion will provide an additional

opportunity to intervene if treatment is deemed

appropriate (Figure 7). Tumor factors that should

prompt consideration for treatment include tumor size

>3 cm, median growth rate >5 mm per year,

infiltrative appearance, clinical stage migration, or

aggressive histology on RMB (Table 6).

349,350

30. For patients with a solid or Bosniak 3/4

complex cystic renal mass, clinicians should

prioritize AS/expectant management when

the anticipated risk of intervention or

competing risks of death outweigh the

potential oncologic benefits of active

treatment. In asymptomatic patients, the

panel recommends periodic clinical

surveillance and/or imaging based on shared

decision making. (Clinical Principle)

It is recognized that surveillance of a likely (or

confirmed) renal malignancy poses some risk of

progression and death from disease. However, for

patients with limited life expectancy, those who

represent unacceptable surgical risks, or those who

potentially face ESRD and initiation of HD, surveillance/

expectant management is a rational non-interventional

nephron-sparing strategy that can save the patient

potentially serious perioperative risks of intervention.

Many localized small renal masses are relatively

indolent at inception and of less clinical significance

compared to other competing comorbidities in

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

Table 6. Patient and tumor related factors favoring AS/Expectant Management versus Intervention

Patient-related factors Tumor factors

Favor AS/ Expectant

Management

 Elderly

 Life expectancy < 5 years

 High calculated comorbidities

 Excessive perioperative risk

362

 Poor functional status

 Marginal renal function (>CKD3b)

 Patient preference to avoid treat-

ment risks

 Maximal tumor diameter < 3 cm

 Non-infiltrative on imaging

 Intralesional fat suggestive of an AML

 Favorable histology (if RMB per-

formed)

 Predominantly cystic features

 Median tumor growth < 5 mm per

year

Favor Intervention

 Young

 Life expectancy > 5 years

 Healthy: low calculated comorbid-

ity

 Acceptable perioperative risk

 Good functional status

 Anticipate adequate renal function

following intervention

 Patient preference for treatment

 Maximal tumor diameter > 3 cm

 Infiltrative on imaging

 Suspicion for advanced T stage

 Unfavorable histology (if RMB per-

formed)

 Median tumor growth > 5 mm per

year

populations at risk.

9,150,355

Thus, in some patients, the

competing risks of death from comorbidities (e.g.,

cardiovascular disease, chronic obstructive pulmonary

disease, or CKD) outweigh the potential oncological and

survival impact of a localized small renal mass. Hence,

expectant management (observation) with serial

imaging is a preferred initial management option for

such patients (Figure 7).

The decision to prioritize observation when the

anticipated risk of intervention or competing risks of

death outweigh the potential oncologic benefits of

active treatment should jointly involve the physician,

the patient and caregivers. Steps to ensure that

patients and loved ones are well informed are

important in engaging them as active participants in

this strategy. Studies show a link between good

communication between patient and physician and

eventual care outcomes.

348

Clinicians should orient and

subsequently re-orient patients regarding AS, and also

consider having both print and online resources

available to facilitate patient education. Patients and

caregivers should be included in the discussions and

encouraged to keep good records, noting improvements

or diminishments in symptoms or health conditions

once observation begins.

Discussions regarding a planned course of observation

should occur with the same depth and intensity of those

regarding treatment. Patients should experience a

supportive, empowered environment. The clinician

should share details of test results and take the time to

ensure the patient understands the dynamic context in

which the information is being provided. To ensure

comprehension, clinicians should speak slowly, avoid

overly technical terminology, and consider providing a

printed summary of key elements of the discussion.

Having the patient verbally reiterate key information

should also be considered to ensure that the goals of

AS/expectant management are understood.

31. For patients with a solid or Bosniak 3/4

complex cystic renal mass in whom the risk/

benefit analysis for treatment is equivocal and

who prefer AS, clinicians should consider RMB

(if the mass is solid or has solid components)

for further oncologic risk stratification. Repeat

cross-sectional imaging should be obtained

approximately 3-6 months later to assess for

interval growth. Periodic clinical/imaging

surveillance can then be based on growth rate

and shared decision-making with intervention

recommended if substantial interval growth is

observed or if other clinical/imaging findings

suggest that the risk/benefit analysis is no

longer equivocal or favorable for continued

AS. (Expert Opinion)

For patients with clinical T1 solid and complex cystic

renal masses, AS appears to be a safe and effective

option for selected patients who have been properly

informed of the risks and benefits of each management

strategy. In patients for whom the risk/benefit analysis

for treatment is equivocal and who prefer AS, diligent

follow-up at 3-6 months is recommended. Patients

should be informed that the risks of metastatic

progression in the short-term (median 24-36 months)

are low (<3%), but not zero.

78,80,159,349,350,356

Absolute

tumor size, tumor complexity, infiltrative appearance

and median growth may all predict progression (Table

6).

349,350

An initial period of AS with delayed intervention has

been shown to be associated with acceptable oncologic

outcomes, albeit with a small risk of upstaging in

selected patients.

78,159,349-351,355,356,361

Absolute triggers

for intervention have not been prospectively defined.

The decision to intervene is complex and based on

multiple risks and tradeoffs.

When calculating growth rate as a trigger for

intervention, the clinician should recognize that normal

variations in maximal tumor diameter and volume

calculations exist between imaging modalities and that

interreader variability may be significant. Moreover,

spider plots of tumor growth rates suggest that

localized renal masses under AS do not always exhibit

linear growth but rather may undergo episodic and/or

Gomertzian (sigmoid-shaped) growth patterns.

159,349,357-

360

Good clinical practice is for the urologist to review

films in sequence, preferably comparing similar

modalities, contrast phases and images over time to

calculate a median growth if this is the primary trigger

for intervention.

Whereas histology may improve stratification for

success or failure of AS, clinicians should consider RMB

in patients with an equivocal clinical risk/benefit

analysis who prefer AS.

200

Pursuing AS in such patients

without tissue confirmation will potentially expose them

to ongoing anxiety associated with an uncertain

diagnosis. Similarly, the knowledge of higher risk

histopathology may recalibrate the AS versus treatment

risk/benefit analysis. Please refer to guideline

statements 10 and 13, which include pertinent details

regarding the processes, risks and performance

characteristics of RMB and further considerations for

patient counseling.

32. For patients with a solid or Bosniak 3/4

complex cystic renal mass in whom the

anticipated oncologic benefits of intervention

outweigh the risks of treatment and

competing risks of death, clinicians should

recommend intervention. AS with potential for

delayed intervention may be pursued only if

the patient understands and is willing to

accept the associated oncologic risks. In this

setting, clinicians should encourage RMB (if

the mass is predominantly solid) for additional

risk stratification. If the patient continues to

prefer AS, close clinical and cross-sectional

imaging surveillance with periodic

reassessment and counseling should be

recommended. (Moderate Recommendation;

Evidence Level: Grade C)

Despite significant advances in the systemic

management of advanced kidney cancer, metastatic

RCC of any histology remains incurable. For this reason,

in patients in whom the oncologic benefits of

intervention outweigh the risks of treatment and

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

competing risks of death, clinicians should recommend

a proactive approach. Factors which favor intervention

may be patient-related or tumor-related (Table 6).

Patients with relatively low co-morbidity and an

anticipated life expectancy >5 years should be

prioritized for treatment, particularly when the renal

mass is >3 cm and/or demonstrates median growth of

> 5 mm/year. In these settings, AS may place the

patient at increased risk of local and distant

progression, and treatment may thus provide an

oncologic and survival advantage.

262,356,361

Increasing

tumor size correlates with increased incidence of high

nuclear grade, less favorable histology, and locally-

advanced features.

9,150

Infiltrative appearance on

imaging also suggests high nuclear grade and/or poorly

differentiated elements, such as sarcomatoid

features.

150,263

Median growth rates exceeding 5mm/

year are indicative of oncologically-active tumors and

have been associated with tumor progression and

metastasis.

159,349,350

In these patients, the decision to

pursue RMB should be individualized.

FOLLOW-UP AFTER INTERVENTION

General Principles

33. Clinicians coordinating follow-up for patients

who have undergone intervention for a renal

mass should discuss the implications of stage,

grade, and histology including the risks of

recurrence and possible sequelae of

treatment. Patients with pathologically-

proven benign renal masses should undergo

occasional clinical evaluation and laboratory

testing for sequelae of treatment but most do

not require routine periodic imaging. (Expert

Opinion)

After intervention, providers should discuss with

patients the information available on the pathology

report, including tumor histology, stage, grade, and

surgical margin status, as well as risk of recurrence

based on established nomograms/calculators. In

addition, post-procedural renal function and nephrology

referral should be discussed, as needed.

Given the reduced oncologic potential, routine

postoperative imaging is not required in most patients

after surgical treatment for a benign renal mass.

However, such patients should undergo at least one

postoperative visit to assess patient recovery and

laboratory testing to assess renal function. Further

surveillance for adverse sequelae of treatment, such as

progressive decline in renal function, may also be

required selectively. In addition, patients who have

only had a biopsy without definitive management, may

carry a small risk of a missed malignancy and should be

considered for attenuated surveillance.

34. Patients with treated malignant renal masses

should undergo periodic medical history,

physical examination, laboratory studies, and

imaging directed at detecting signs and

symptoms of metastatic spread and/or local

recurrence as well as evaluation for possible

sequelae of treatment. (Clinical Principle)

Interval patient history and physical examination are an

integral part of medical care, offering the opportunity to

yield critical information regarding the presence of

disease recurrence or adverse events related to

treatment effects. A myriad of signs and symptoms,

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

Figure 6. Meta-analysis of local recurrence-free survival for PN versus combined efficacy of primary

and/or repeat TA among studies with follow-up of 48 months ± 12 months.

Abbreviations: CI, confidence interval; IV, inverse variance; PN, partial nephrectomy; TA, thermal ablation.

Note: Total patients is defined as total patients with biopsy proven RCC treated with each modality. Events refer to

number of patients with local recurrence.

both organ-specific and systemic, including weight loss,

night sweats, shortness of breath, pleuritic chest pain,

hemoptysis, epistaxis, dermatologic involvement,

musculoskeletal pain, weakness, or focal neurological

deficits may herald disease recurrence/progression and/

or the development of a complication and serve as an

indication for further investigation. Physical

examination should assessment for masses in the

abdomen/abdominal wall, lymphadenopathy

(supraclavicular, axillary, groin), or lower extremity

edema that might suggest recurrence with IVC

involvement. Specific recommendations for

surveillance abdominal and chest imaging are provided

in statements 43 and 44.

35. Patients with treated malignant renal masses

should have periodic laboratory testing

including serum creatinine, eGFR, and

urinalysis. Other laboratory evaluations (e.g.,

complete blood count, lactate dehydrogenase,

liver function tests, alkaline phosphatase and

calcium level) may be obtained at the

discretion of the clinician or if advanced

disease is suspected. (Expert Opinion)

Please see the renal assessment background sections

for a discussion of the benefits of monitoring renal

function and referral to nephrology. This should include

periodic assessment of serum creatinine levels, eGFR,

and urinalyses to evaluate for proteinuria, hematuria,

or inflammatory changes.

LDH is included in several nomograms where it provides

prognostic information, in particular for patients with

advanced disease.

363,364

However, there are no data

that demonstrate that regular LDH measurements in

the non-metastatic setting improve detection of

metastatic disease, and this test should thus be used

selectively. Although no strong evidence exists for the

use of these laboratory tests in the follow-up of patients

with clinically localized renal cancers, a common-sense

approach dictates that measures of general organ

function are part of routine follow-up for patients who

are diagnosed with cancer.

While elevated pre-operative alkaline phosphates

365

is a

potential prognostic marker for RCC, retrospective

reviews do not demonstrate utility of either bone scan

or alkaline phosphatase in the initial evaluation or

routine follow-up of asymptomatic patients with

RCC.

366,367

36. Patients undergoing follow-up for treated

renal masses with progressive renal

insufficiency or proteinuria should be referred

to nephrology. (Expert Opinion)

The long-term impact of renal dysfunction increases

risks of osteoporosis, anemia, metabolic and

cardiovascular disease, hospitalization and death.

Effective treatment strategies are available to slow the

progression of CKD and reduce cardiovascular risks,

and therefore timely identification of progressive renal

dysfunction and/or proteinuria can provide opportunity

for medical intervention when indicated. The two

formulas for monitoring eGFR commonly reported in the

contemporary literature at this time are the

Modification of Diet in Renal Disease and CKD –

Epidemiology Collaboration (CKD-EPI) equations. Please

refer to the Presentation and Diagnosis section for

additional information.

37. Patients undergoing follow-up for treated

malignant renal masses should only undergo

bone scan if one or more of the following is

present: clinical symptoms such as bone pain,

elevated alkaline phosphatase, or

radiographic findings suggestive of a bony

neoplasm. (Moderate Recommendation;

Evidence Level: Grade C)

Studies that address the utility of an initial bone scan in

the evaluation of patients with of RCC show that,

although bone scan has a reasonable sensitivity and

specificity, the probability of finding bony neoplasms in

the absence of elevated alkaline phosphatase or bone

pain is low.

96-99

As such, the routine use of bone scan in

the absence of bone pain or elevated ALP should not be

pursued. However, with the presence of symptoms and/

or elevated markers, radionuclide bone scan can be a

useful test.

96,368

This recommendation is based on studies indicating

that an elevated alkaline phosphatase or the presence

of clinical symptoms, such as bone pain, raises the

probability of metastatic spread to a level >5%-10%.

Assuming a sensitivity of 94% and a specificity of 86%

with a pre-test probability of 5%, a negative bone scan

would drop the post-test probability below 1%, whereas

a positive test would raise the post-test probability to

26%, likely necessitating further diagnostic evaluation.

In this setting, the Panel judged the benefit to risk/

burden ratio to favor the performance of a bone scan in

the setting of symptoms or elevated alkaline

phosphatase.

369

There are no compelling data that supports the routine

use of bone scan in the follow-up of patients with non-

metastatic disease. This recommendation is based on

studies indicating that in the absence of an elevated

ALP or clinical symptoms, such as bone pain, the

prevalence of bony metastases is very low (<1%).

Routine imaging of these patients would result in a high

rate of false-positive findings necessitating further

burdensome, potentially invasive and resource

intensive studies.

38. Patients undergoing follow-up for treated

malignant renal masses with acute

neurological signs or symptoms should

undergo prompt magnetic resonance imaging

(MRI) or computed tomography (CT) scanning

of the brain and/or spine. (Strong

Recommendation; Evidence Level: Grade A)

This recommendation is based on high diagnostic

accuracy of neurologic cross-sectional (CT or MRI)

imaging to identify or exclude metastases to the brain

and/or spine, in addition to a high prevalence of

underlying management-altering pathology in patients

with these symptoms, including but not limited to

metastatic disease. MRI may be more sensitive than CT

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

scan for the detection of small CNS neoplasms. CT may

be used in the setting of acute neurological signs or

symptoms to diagnose abnormalities that require

emergent treatment,

370,371

but MRI is the most sensitive

and specific imaging test for detection of metastatic

neoplasms to the brain.

372

39. For patients undergoing follow-up for treated

malignant renal masses, additional site-

specific imaging can be ordered as warranted

by clinical symptoms suggestive of recurrence

or metastatic spread. Positron emission

tomography (PET) scan should not be

obtained routinely but may be considered

selectively. (Moderate Recommendation;

Evidence Level: Grade C)

Occasionally, patients will present with symptoms that

could be attributed to metastatic disease. These

symptoms may include, but are not limited to, new

onset bone pain, weight loss, anorexia, abdominal

discomfort, asthenia, fatigue, gross hematuria and

lower extremity edema. When patients present with

symptoms that could be attributed to disease

recurrence or metastasis, site-specific imaging should

be obtained, and the modality of imaging (CT, MRI, US,

bone scan, plain films) should be tailored to the specific

presenting symptoms.

PET scan should not be routinely obtained in the follow-

up of patients after RCC treatment, as a review of the

evidence failed to identify studies to conclusively

support a role for FDG-PET in this setting.

373

The main

limitations of FDG are its lack of sensitivity and

specificity for detecting RCC. False positive results can

be seen in postsurgical scarring,

374

and concurrent

infectious or inflammatory processes,

375,376

while false

negative results can be seen with small recurrence

374,375

and can be inherent to PET scanner limited resolution

or close proximity of the recurrence to the collecting

system and urinary tract which routinely lights up on

PET.

374

Well-designed prospective studies on the role of FDG

PET/CT are still needed prior to routine clinical use in

the follow-up of patients with kidney cancer after

definitive treatment. Future roles may exist for PET/CT

with newer imaging agents, such as Zirconium

girentuximab, which are currently being studied in

prospective trials.

374

40. Patients with findings suggestive of

metastatic renal malignancy should be

evaluated to define the extent of disease and

referred to medical oncology. Surgical

resection or ablative therapies should be

considered in select patients with isolated or

oligo-metastatic disease. (Expert Opinion)

After undergoing a thorough investigation with medical

history, physical examination, laboratory studies, and

imaging, patients with findings suggestive of metastatic

disease should be referred to a medical oncologist for

additional evaluation and management. For

appropriately selected patients with good performance

status and isolated or oligo-metastatic disease, surgery

and ablation should be considered after

multidisciplinary discussion.

378

Complete resection of

solitary or isolated metastases can lead to 5-year

disease-free status in 20-30% of patients with results

varying based on several prognostic factors, including

performance status, time from initial treatment to

metastasis, number and size of metastatic lesions, site

of metastases, and factors reflecting the tumor biology

of the primary lesion, including stage, grade, and

histology.

41. Patients with findings suggesting a new renal

primary or local recurrence of renal

malignancy should undergo metastatic

evaluation including chest and abdominal

imaging. If the new primary or recurrence is

isolated to the ipsilateral kidney and/or

retroperitoneum, a urologist should be

involved in the decision-making process, and

surgical resection or ablative therapies may

be considered. (Expert Opinion)

Local recurrence is defined as any persistent or

recurrent disease present in the treated kidney or

associated renal fossa after initial treatment. Local

recurrence or persistence after TA includes persistent

enhancement of any treated mass, a visually enlarging

neoplasm or new nodularity, or failure of regression in

size of the treated lesion(s), or new satellite or port site

lesions. Patients who are found to have a new renal

primary tumor, or a local recurrence as defined above

should undergo a metastatic evaluation (CT chest and

either CT or MRI abdomen are preferable). Additional

imaging can be obtained as needed. For appropriately

selected patients with good performance status and an

isolated new renal primary tumor or a local recurrence,

surgery or ablation should be considered for definitive

management.

Follow-up After Surgery

42. Clinicians should classify patients who have

been managed with surgery (PN or RN) for a

malignant renal mass into one of the following

risk groups for follow-up:

If final microscopic surgical margins are positive

for cancer, the risk category should be considered

at least one level higher, and increased clinical

vigilance should be exercised. (Expert Opinion)

The literature previously suggested that a variety of

algorithms or nomograms could provide relatively

Low Risk

(LR):

pT1 and Grade 1/2

Intermedi-

ate Risk

(IR):

pT1 and Grade 3/4, or pT2

any Grade

High Risk

(HR):

pT3 any Grade

Very High

Risk (VHR):

pT4 or pN1, or sarcomatoid/

rhabdoid dedifferentiation, or

macroscopic positive margin

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

robust and accurate prediction of risk of recurrence

after surgical management of RCC. However, Correa

and colleagues recently studied 8 of these RCC

recurrence models (UISS, SSIGN, Leibovich, Kattan,

MSKCC, Yaycioglu, Karakiewicz, and Cindolo) as applied

to the results of a phase III adjuvant therapy clinical

trial, with direct comparison of what would be predicted

by stage alone.

Model performance ranged from a c-

index of 0.556 (UISS) to 0.688 (SSIGN). Most of these

models only marginally outperformed the 2002 TNM

staging system (c-index of 0.60). With these data in

mind, the Panel formulated a simple grouping to keep

risk stratification convenient for routine patient care,

while differentiating risk groups in a clinically

meaningful fashion. The same follow-up schedule

applies to all RCC histologies. Data regarding the risk of

recurrence in each of these cohorts is listed below.

LR: Patients w ith pT1 have a recurrence rate of

9.2%, while patients with Grade 1 and Grade 2 have

recurrence rates of 6.4% and 15.4%, respectively.

379

IR: P atients w ith pT2 have a recurrence rate of

32%, while patients with organ-confined RCC, Grade

3/4 tumors have recurrence rates of approximately 20-

30%. Recurrence rates for Grade 4 tumors may be

higher in certain circumstances (larger tumor or non-

organ confined) and can be considered at least one risk

category higher at physician discretion.

379

VHR: M ost patients w ith pT4 present w ith

metastatic disease at the time of surgery. Of those who

are initially free of disease after surgical resection,

64.7% have disease recurrence (mostly distant alone,

but local often seen too).

380

Patients with nodal

involvement (pN1) who undergo complete surgical

resection have median cancer-specific survival of 2.8

years, with 64.3% dying of RCC after recurrence.

381

one study, patients with sarcomatoid dedifferentiation

were found to have a 72% recurrence rate, with a

median time to recurrence of 26.2 months.

382

Over

seventy percent presented with a single site of disease

at time of first recurrence (lung, 45%; local, 25%;

bone, 13%; liver, 13%).

383

In patients with grade 4 non

-metastatic RCC, sarcomatoid dedifferentiation was

associated with an 82% increased cancer-specific

death. Wood and colleagues studied patients with

positive surgical margins after PN and reported a tumor

bed recurrence rate of 15.9% (versus 3% in a matched

control group), indicating the need for closer follow-up

in patients with positive surgical margins after PN. The

risk for patients with macroscopic positive margins is

even higher, as these patients have residual disease

and are very high-risk for developing clinical local

recurrence.

43. Patients managed with surgery (PN or RN) for

a renal malignancy should undergo abdominal

imaging according to Table 1, with CT or MRI

pre- and post-intravenous contrast preferred.

(Moderate Recommendation; Evidence

Strength: Grade C). After 2 years, abdominal

ultrasound (US) alternating with cross-

sectional imaging may be considered in the LR

and IR groups at physician discretion. After 5

years, informed/shared decision-making

should dictate further abdominal imaging.

(Expert Opinion)

Merrill and colleagues studied the difference in survival

outcomes in 78 patients (of 737 surgically treated

patients) presenting with a symptomatic versus

asymptomatic recurrence.

384

Symptomatic recurrences

were associated with a 3-fold increased risk of cancer-

specific mortality. These results were consistent for

both local and systemic recurrences. Other studies

support the notion that the size of a local recurrence is

associated with survival outcomes, underscoring the

potential benefits of routine scheduled postoperative

surveillance for the detection of early recurrences while

still asymptomatic.

385

Beisland and colleagues prospectively followed 312

patients surgically treated for non-metastatic RCC using

a risk-stratified approach (using Leibovich risk

groups).

386

They noted that patients who were

diagnosed with a recurrence during the scheduled

follow-up program experienced longer survival and

were more frequently able to receive tumor-directed

therapy than those who were not. Such studies support

a proactive approach to follow-up after intervention,

which reflects most urologists’ clinical experience.

Duration of follow-up after intervention for RCC has

been controversial. Previous guidelines suggested that

surveillance can be either terminated or strongly

attenuated relatively soon (3-5 years) after surgery.

However, recent studies suggest that 30% of RCC

recurrences are diagnosed beyond 5 years after

surgery. Stewart and colleagues studied an institutional

cohort of 3,651 patients treated surgically for non-

metastatic RCC.

Patients were classified based on AUA

risk, and the recurrence detection rates based on

AUA,

387

NCCN 2013 and NCCN 2014 guidelines were

compared.

181

Of note, all 3 guidelines do not offer

scheduled imaging after 5 years from date of surgery.

29.8% of patients experienced cancer recurrence at a

median of 1.9 years after surgery. The authors found

that the 2013 NCCN, 2014 NCCN, and the AUA

guidelines captured 35.9%, 68.2%, and 66.9% of all

recurrences, respectively. Extending surveillance

protocols up to 10 years would have improved

recurrence detection rates to around 90%.

The option to use abdominal US instead of CT or MRI at

physician discretion after 5 years of follow-up is

intended to allow continuous monitoring after 5 years,

while minimizing radiation exposure/cost in the LR and

IR groups.

44. Patients managed with surgery (PN or RN) for

a renal malignancy should undergo chest

imaging (chest x-ray [CXR] for LR and IR; CT

chest preferred for HR and VHR) according to

Table 1. (Moderate Recommendation;

Evidence Strength: Grade C). After 5 years,

informed/shared decision-making discussion

should dictate further chest imaging and CXR

may be utilized instead of chest CT for HR and

VHR (Expert Opinion)

As pulmonary metastases are the most common site of

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

renal cancer recurrence, timely detection of recurrent

disease in the chest is optimized by a chest CT, which

can be performed at the same time as the abdominal

imaging and should be prioritized whenever CXR is

equivocal or suspicious. The option to use CXR instead

of chest CT after 5 years of follow up is intended to

allow continuous monitoring after 5 years, while

minimizing radiation exposure/cost in the HR and VHR

groups.

As the utility of adjuvant therapy is still limited, early

detection of metastatic disease is vital for improving

patient outcomes. Chest and abdominal metastases are

usually asymptomatic while small, with symptoms

developing mainly in advanced stages.

388

Early

intervention when surgical resection or ablation is

feasible could improve patient outcomes.

389

Follow-up After TA

45. Patients undergoing ablative procedures with

biopsy that confirmed malignancy or was non-

diagnostic should undergo pre- and post-

contrast cross-sectional abdominal imaging

within 6 months (if not contraindicated).

Subsequent follow-up should be according to

the recommendations for the IR postoperative

protocol (Table 1). (Expert Opinion)

The Panel considers urologists to be the experts in the

evaluation, management and follow-up of both the

small renal mass as well as renal cancer and the

treatment associated complications. Urologists should

be involved in the care of the patient whether or not

they perform the actual procedure. They should be

active partners of interventional radiologists, and

participation in the percutaneous procedure is

encouraged.

This recommendation is based on a 5-10% failure rate

of ablative therapy and places a high value on the early

detection by CT or MRI scans to direct potential

retreatment and successful salvage. Close attention to

overall pattern and morphology, with respect to

growth/shrinkage and nodularity of the neoplasm over

time, as well as contrast enhancement on serial follow-

up scanning is advised. Patients who cannot receive IV

contrast due to renal dysfunction or allergies should still

undergo cross-sectional MRI (preferably, and ideally

contrast-enhanced) or CT scan to assess for regression

of the treated lesion and to monitor for new nodularity

or growth. As previously stated, any growth in the size

of the treated lesion, lack of regression in size of the

lesion over time, new nodularity (in the kidney itself,

the surrounding soft tissue, or the port sites) or

enhancement beyond six months from ablation would

be concerning and should prompt further investigation,

including a biopsy as needed.

Patients who have undergone ablative treatment of

renal tumors are subsequently followed with radiologic

scanning using CT or MRI. Immediate post-procedural

imaging of the ablated tumor generally shows the

treatment bed to be larger than the pre-treatment

tumor size for RFA due to ablation of a peripheral

margin of normal tissue, and for cryoablation due to

extension of the iceball beyond the original tumor

margin. Radiological evolution of cryoablated tumors is

characterized by significant shrinkage and loss of

contrast enhancement on CT. Tumors successfully

treated with RFA demonstrate no IV contrast

enhancement but there is often minimal shrinkage

observed on cross-sectional imaging.

390

On MRI, the

imaging hallmark of successful renal tumor ablation is

lack of tumor enhancement with gadolinium-enhanced

imaging. Rim enhancement, believed to represent

reactive change, may occasionally be seen at early

postprocedural MR scanning after RFA or cryoablation,

which later resolves.

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

Table 1: Recommended follow-up schedule after surgery for renal cancer (in months)*

*Follow-up timeline is approximate and allows flexibility to accommodate reasonable patient, caregiver, and in-

stitutional needs. Each follow-up visit should include relevant history, physical examination, laboratory testing,

and abdominal and chest imaging. Overall, 30% of renal cancer recurrences after surgery are diagnosed beyond

60 months.

Informed/shared decision-making should guide surveillance decisions beyond 60 months.

Risk 3 6 9 12 18 24 30 36 48 60 72-84 96-120

LR x x x x x x

IR x x x x x x x x

HR x x x x x x x x x x

VHR x x x x x x x x x x x x

FUTURE DIRECTIONS

The most promising routes to advance the field in

localized renal cancer include (1) clinical trials, (2)

collaborative quality initiatives, (3) novel diagnostics/

biomarkers, and (4) improved technologies and

systemic therapies. Each of these requires an

unrelenting commitment to continuous clinical

improvement and scientific investigation.

The management of localized renal cancer is an area for

which there is a paucity of randomized clinical trials

(RCT’s). Improving the strength of evidence will require

an increased commitment to clinical trial design,

conduct, and funding. Although our understanding of

the nature and management of this disease continues

to progress, without adequate engagement and

support, our treatment paradigms will likely continue to

be more art than science.

An appropriate companion to RCT’s is the development

of collaborative quality initiatives (CQI’s).

391

Within a

CQI, participating hospitals and providers collect, share,

and analyze data through clinical registries. CQI

participants design and affect changes that improve

outcomes of complex, highly technical areas of care.

392

CQI registries allow for a more robust analysis of the

link between processes and outcomes than can occur

with retrospective single or multi-institutional studies;

particularly as more sensitive and specific diagnostics/

biomarkers are complemented by technologic

advances. Scientific inquiry will continue to provide

fundamental knowledge regarding the biological basis,

inherent risks, and natural history of localized renal

masses such that appropriate trade-offs can be made

when considering optimal management.

Evaluation and Diagnosis

The localized renal mass remains primarily a

radiographic diagnosis. The field of tumor radiomics,

artificial intelligence and molecular imaging promises

393

to improve our ability to discriminate tumor histology,

grade

394,395

and ultimately gene and protein expression

with prognostic implications. The development of more

sophisticated modeling of patient demographic features

as recorded in the electronic medical record, such as

age, gender, race, body mass index, comorbidities,

exposure to tobacco, and other risk factors are being

studied to contextualize and individualize management

options. Finally, tumor markers detected in biopsy,

blood, or urine should be studied to improve prognostic

models for RCC. Efforts based on gene and protein

expression have identified multiple promising markers

that may one day distinguish between subtypes of

malignant and benign renal tumors.

396,397

Recent work

through The Cancer Genome Atlas (TCGA)

398,399

identify genomic markers for clear cell RCC

400

, papillary

RCC

401

, and chromophobe RCC

402

holds great clinical

potential for more accurate diagnosis, prognostication,

and surveillance of renal masses. The promise of

measuring circulating tumor cells, or liquid tumor

biopsies, for diagnosis and surveillance for recurrence

and response to treatment is likely several years off,

but could substantially transform care models.

403-406

Counseling and Outcomes-Based Research

As data emerge regarding variability in treatments

performed for localized renal cancer, the impact of the

individual physician-patient interaction becomes more

evident. The quality of patient counseling can only be

improved by providing high quality data, particularly

from RCT’s. Given our current state of knowledge,

translation of information from research studies and

guidelines into practical materials for patients is not

straight-forward. The development of decision aids for

informed medical-decision making is ongoing.

407,408

The

appropriate application of data from large registries and

implementation sciences to improve processes and

standardization of care is an important initiative that

must move forward. Increased quality of data, including

improved assessment of tumor biology and prospective

trials of management options, is greatly needed to

facilitate more intelligent patient counseling.

Management

A major limitation of the literature supporting the

current guidelines for management of localized renal

cancer is the relatively low level of evidence.

Prospective comparative trials, ideally randomized,

comparing AS vs. active intervention (TA or excision)

should be prioritized to provide higher quality data

about oncologic and renal functional outcomes and to

assess the treatment-related morbidities or limitations

of each approach. With improved reporting and more

extended follow-up, multi-institutional observational

data will strengthen confidence in recommendations,

but not nearly to the extent that clinical trials can

provide.

Comparison of extirpative treatment modalities should

include prospective evaluation of PN versus RN,

prioritized in patients with a normal contralateral kidney

and no preexisting CKD/albuminuria, with the goal of

assessing the impact of new baseline functional status

on overall survival, cardiovascular health, and

subsequent renal stability on a longitudinal basis.

Ideally, patients with tumors with increased oncologic

potential (cT1b/T2) should be prioritized for such

trials.

259,409,410

Regarding nephron-sparing surgery,

improved data comparing the relative merits and

limitations of standard PN versus tumor enucleation

should be sought, ideally through prospective

evaluation incorporating improved reporting, and

standard assessment of surgical margins.

248

Multiple non-extirpative methods being actively

investigated in the management of renal masses

include stereotactic body radiation therapy (SBRT),

HIFU, microwave ablation (MWA), and laser interstitial

thermal therapy (LITT). These approaches differ in their

mechanisms of action, invasiveness, reported outcomes

and experience. Their use should be approached

systematically and with caution, and they should be

considered investigational at present. SBRT, also

frequently referred to as stereotactic ablative

radiotherapy (SABR), has been reported in a small

number of series. SBRT involves relatively intense

protocols (24 to 40 Gy) over one to five fractions and a

high degree of spatial precision, offering the potential

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

to be less invasive than surgical or conventional

ablative approaches.

411

Despite encouraging results, the

current body of evidence is limited due to small patient

numbers, short follow-up and inconsistent methods of

reporting outcomes.

411

Thus, SBRT in the management

of localized renal masses at present remains

investigational and should be primarily considered for

patients who are medically inoperable and are not

candidates for established TA approaches. Investigation

through clinical trials should be prioritized.

Similarly, HIFU remains investigational in the

management of renal masses, although it is currently

used clinically to treat prostate cancer and uterine

fibroids.

412

HIFU relies on the use of a lens or focused

transducer to deliver high-frequency sound waves to

tissue, typically 1 to 5 MHz. HIFU may be administered

in an entirely noninvasive means similar to

extracorporeal lithotripsy, thus minimizing the risk of

tumor seeding, urinary extravasation or

hemorrhage.

413I

nitial clinical investigations have

established the feasibility of transcutaneous HIFU;

however, distinct regions of renal masses are

frequently left untreated resulting in incomplete

ablation.

414-417

Similar to RFA, MWA delivers electromagnetic energy

through flexible probes inserted into a target lesion.

MWA produces target temperatures (>60° C) more

rapidly than RFA, and, thus, appears to have significant

potential as an ablative modality.

418

LITT uses optical

fibers that are inserted directly into the target tissue to

deliver laser light that is converted into thermal energy.

The most common laser type used in LITT is a

neodymium: yttrium-aluminum-garnet (Nd:YAG)

laser.

419

Outcomes of clinical investigations are limited

due to the small number of treated patients and short

follow-up.

420,421

Given the limited number of published

studies involving HIFU, MWA and LITT and lack of long-

term follow-up, appropriate use of these modalities in

the management of small renal masses remains poorly

defined. Larger prospective trials will be necessary to

develop and assess optimal use, risks and morbidity.

Follow-Up After Intervention

The proposed guidelines for follow-up after intervention

for renal cancer attempt to provide a risk-based

approach to surveillance and monitoring. Few high-

quality studies currently exist to help formulate

surveillance regimens, and many of the Panel’s

recommendations are thus based primarily on expert

opinion. Any cancer surveillance regimen is a balancing

act that includes many variables such as the likelihood

of disease recurrence at various sites, temporal

considerations, the potential benefits of therapeutic

interventions and effectiveness of these modalities

based on timing of recurrence detection, improvements

in diagnostic and initial interventions, patient

characteristics, and the burden and cost of monitoring.

As electronic medical records and quality and safety

initiatives intensify, tracking outcomes of all patients

will become increasingly codified and more usable for

research purposes. These data can then also be used

to inform the proper sequencing, timing, duration, and

type of follow-up that improves patient outcomes with

the most parsimonious monitoring.

Future research to make patient follow-up more

efficient and effective could include one or many of

these modalities: develop circulating biomarkers to

supplement currently available imaging, develop novel

functional imaging, conduct clinical trials to compare

currently available imaging modalities, as well as

clinical trials to guide the frequency of imaging/follow-

up, similar to studies done in testicular cancer (MRC

TE08)

422

, colon cancer (GLIDA)

423

, and non-small cell

lung cancer (IFCT-0302).

424

SUMMARY

In conclusion, improving the management of localized

renal tumors will require a concerted effort among

clinicians and allied fields to develop higher quality

evidence and facilitate more precise estimations of

relative risks and benefits of each therapeutic

approach.

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

Abbreviations

Acve Surveillance AS

Agency for Healthcare Research and Quality AHRQ

American College of Radiology ACR

American Society of Nephrology ASN

American Urological Associaon AUA

Angiomyolipoma AML

Birt Hogg-Dubé BHD

Chest X-Ray CXR

Chronic Kidney Disease CKD

College of American Pathologists CAP

Computed Tomography CT

End-Stage Renal Disease ESRD

Esmated Glomerular ltraon rate eGFR

Fine Needle Aspiraon FNA

Glomerular Filtraon Rate GFR

Hereditary Leiomyomatosis RCC HLRCC

Hereditary Papillary Renal Carcinoma HPRC

High Risk HR

High-Intensity Focused Ultrasound HIFU

Intermediate Risk IR

Laser Intersal Thermal Therapy LITT

Low Risk LR

Magnec Resonance Imaging MRI

Microwave Ablaon MWA

Paral Nephrectomy PN

Positron Emission Tomography PET

Pracce Guidelines Commiee PGC

Radical Nephrectomy RN

Radiofrequency Ablaon RFA

Randomized Controlled Trials RCT

Renal Cell Carcinoma RCC

Renal Mass Biopsy RMB

Society of Intervenonal Radiology SIR

Society of Urologic Oncology SUO

Stereotacc Body Radiaon Therapy SBRT

Thermal Ablaon TA

Ultrasound US

Very High Risk VHR

von Hippel-Lindau VHL

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

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Renal Mass and

Localized Renal Cancer

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Renal Mass and Localized Renal Cancer: Evalua-

tion, Management, and Follow-Up Panel, Consult-

ants, and Staff 2021

Steven Campbell, MD (Chair)

Cleveland Clinic Foundation

Cleveland, OH

Robert G. Uzzo, MD

Fox Chase Cancer Center

Philadelphia, PA

Peter Earl Clark, MD

Atrium Health

Charlotte, NC

Sam S. Chang, MD

Vanderbilt University Medical Center

Nashville, TN

Jose A. Karam, MD

MD Anderson Cancer Center

Houston, TX

Consultants

Lesley Souter, PhD

Staff

Marybeth Farquhar, PhD, MSN, RN

Erin Kirkby, MS

Leila Rahimi, MHS

Brooke Bixler, MPH

Emily Calvert, MSN, RN

CONFLICT OF INTEREST DISCLOSURES

All panel members completed COI disclosures. Disclo-

sures listed include both topic– and non-topic-related

relationships.

Consultant/Advisor: Sam S. Chang, MD, MBA:

GLG, Janssen, BMS, Pfizer, Urogen, Virtuoso Surgical,

mIR; Peter E. Clark, MD: Galil Medical, Merck; Jose A.

Karam: Merck, P fizer; Robert G. Uzzo, MD: UroGen

Pharma, Amgen

Scientific Study or Trial: Sam S. Chang, MD, MBA:

NIH; Jose A. Karam, MD: Roche/Genentech, Mirati;

Robert G. Uzzo, MD: Pfizer, Genentech

Investment Interest: Jose A. Karam, MD: MedTek,

Allogene, Romtech

Health Publishing: Sam S. Chang, MD, MBA: Uro

Today; Jose A. Karam, MD: Frontiers in Genitourinary

Oncology, Annals of Surgical Oncology, Cancer, Clinical

Genitourinary Cancer

Meeting Participant or Lecturer: Robert G. Uzzo,

MD: Janssen

Peer Reviewers 2021

We are grateful to the persons listed below who con-

tributed to the Guideline by providing comments during

the peer review process. Their reviews do not neces-

sarily imply endorsement of the Guideline.

AUA Reviewers (Board of Directors, Science and

Quality Council, Practice Guidelines Committee,

Journal of Urology):

Linda Baker, MD

Thomas Chi, MD

John Denstedt, MD

Martin K. Dineen, MD

James A. Eastham, MD

David A. Ginsberg, MD

David F. Green, MD

Melissa R. Kaufman, MD

Louis R. Kavoussi, MD

Barry A. Kogan, MD

Matthew Edward Nielsen, MD

Phillip M. Pierorazio, MD

Anthony Y. Smith, MD

Thomas Stringer, MD

Raju Thomas, MD

External Reviewers (Non-AUA Affiliates):

Jeffrey A. Cadeddu, MD

Anthony Chang, MD

Sherri M. Donat, MD

Brian R. Lane, MD

Kirill Shiranov, MD

Darius Unwala, MD

Renal Mass and Localized Renal Cancer Panel,

Consultants, and Staff 2017

Steven Campbell, MD (Chair)

Cleveland Clinic Foundation

Cleveland, OH

Robert G. Uzzo, MD (Vice Chair)

Fox Chase Cancer Center

Philadelphia, PA

Mohamad E. Allaf, MD

Johns Hopkins University School of Medicine

Baltimore, MD

Jeffrey A. Cadeddu, MD

UT Southwestern

Dallas, TX

Anthony Chang, MD

University of Chicago

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

Chicago, IL

Peter Earl Clark, MD (PGC Rep)

Vanderbilt University Medical Center

Nashville, TN

Brian J. Davis, MD, PhD

Mayo Clinic, Department of Radiation Oncology

Rochester, MN

Ithaar H. Derweesh, MD

University of California San Diego

La Jolla, CA

Leo Giambarresi, PhD (Pt. Advocate)

Debra A. Gervais, MD

Massachusetts General Hospital

Boston, MA

Susie L. Hu, MD

University Medicine

Providence, RI

Brian R. Lane, MD, PhD

Spectrum Health Medical Group - Urology

Grand Rapids, MI

Bradley C. Leibovich, MD, FACS

Mayo Clinic, Department of Urology

Rochester, MN

Phillip M. Pierorazio, MD

Johns Hopkins University School of Medicine

Baltimore, MD

Consultants

Eric B. Bass, MD, MPH

Johns Hopkins Medicine

Baltimore, MD

Staff

Heddy Hubbard, PhD, MPH, RN, FAAN

Abid Khan, MHS, MPP

Erin Kirkby, MS

Shalini Selvarajah, MD

Nenellia K. Bronson, MA

Leila Rahimi, MHS

Brooke Bixler, MPH

CONFLICT OF INTEREST DISCLOSURES

All panel members completed COI disclosures. Disclo-

sures listed include both topic– and non-topic-related

relationships.

Consultant/Advisor: Jeffrey A. Cadeddu, Levita

Magnetics; Peter E. Clark, Galil Medical, Genentech;

Phillip. M. Pierorazio, Myriad Genetics

Meeting Participant or Lecturer: Anthony Chang,

Alexion Pharmaceuticals; Robert G. Uzzo, Janssen

Scientific Study or Trial: Jeffrey A. Cadeddu, Levi-

ta Magnetics; Ithaar H. Derweesh, GalxoSmithKline,

Inc., Pfizer, Inc.

Leadership Position: Brian J. Davis, American Col-

lege of Radiology, American Board of Radiology; Leo I.

Giambarresi, ZERO-The End of Prostate Cancer

Investment Interest: Jeffrey A. Cadeddu, Titan

Medical Inc., Transenterix; Brian J. Davis, Pfizer Inc.

Health Publishing: Anthony Chang, Elsevier

Other: Leo I. Giambarresi, SAR International Inc.

Follow-up for Clinically Localized Renal Neo-

plasms Panel, Consultants and Staff 2013

Sherri Machele Donat, MD (Chair)

Memorial Sloan-Kettering Cancer Center

New York, NY

Sam S. Chang, MD (Vice-Chair)

Vanderbilt University Medical Center

Nashville, TN

Jay Todd Bishoff, MD

Intermountain Medical Group

Salt Lake City, UT

Jonathan A. Coleman, MD

Memorial Sloan-Kettering Cancer Center

New York, NY

Philipp Dahm MD, MHSc

University of Florida

Gainesville, FL

Ithaar H. Derweesh, MD

UCSD Moores Cancer

La Jolla, CA

S. Duke Herrell III, MD

Vanderbilt University Medical Center

Nashville, TN

Susan Hilton, MD

Hospital of the University of Pennsylvania

Philadelphia, PA

Eric Jonasch, MD

University of Texas MD Anderson Cancer Center

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

Houston, TX

Daniel Wei Lin, MD

University of Washington

Seattle, WA

Victor Edward Reuter, MD

Memorial Sloan-Kettering– Pathology

New York, NY

Consultants

Mieya Diaz, PhD

CONFLICT OF INTEREST DISCLOSURES

All panel members completed COI disclosures. Relation-

ships that have expired (more than one year old) since

the panel’s initial meeting, are listed. Those marked

with (C) indicate that compensation was received; rela-

tionships designated by (U) indicate no compensation

was received.

Board Member, Officer or Trustee: Victor E. Reu-

ter, United States and Canadian Academy of P a-

thology (U) (Expired).

Consultant/Advisor: Sam S. Chang, Allergan (C)

(Expired), Amgen (C) (Expired), Astellas (C), Centocor

Ortho Biotech (C) (Expired), Dendreon (C), ENDO (C)

(Expired), GE Health Services (C) (Expired), Predictive

Biosciences (C), Sanofi-Aventis (C) (Expired), Janssen

(Expired); Jonathan Coleman, Endocare (C) (Expired);

Ithaar H. Derweesh, Angiodynamics, I nc. (C)

(Expired), Covidien, Inc. (C) (Expired), Cryolife, Inc.

GlaxoSmithKline, Inc. (U); S. Duke Herrell, Aesculap

Inc. (C), Covidien Surgical Devices (C) (Expired); Eric

Jonasch, Aveo (C), Bayer P harmaceuticals (C),

Bristol Myers Squibb (C), Genentech (C), Glaxo Smith

Kline (C), Novartis (C), Pfizer (C), Wyeth (C) (Expired);

Daniel Lin, Caris Life Sciences (U) (Expired), Den-

dreon Corporation (C), GenProbe (U), Myriad (C), Pfizer

(C);

Meeting Participant or Lecturer: Sam S. Chang,

Janssen (C); Jay Todd Bishoff, Pfizer (C) (Expired);

Daniel Lin, Dendreon Corporation (C), Myriad (C). In-

vestment Interest: S. Duke Herrell, Veran Medical

Technologies (U).

Scientific Study or Trial: Jay Todd Bishoff, P fizer

(C); Jonathan Coleman, Steba (U); Philipp Dahm,

CureVac (C) (Expired); S. Duke Herrell, Galil Medical

(C), Wilex (C) (Expired); Eric Jonasch, Aveo (C), Bristol

Myers Squibb (C), Glaxo Smith Kline (C), Novartis (C),

Pfizer (C) (Expired); Daniel Lin, Department of Defense

(C), GenProbe (U), NIH/NCI (C), Veteran's Affairs (U).

Other, Employee: Mireya Diaz, Henry Ford Hospi-

tal - Vattikuti Urology Institute (C).

Other: Speaker's Bureau: Eric Jonasch, LW yeth

Peer Reviewers

We are grateful to the persons listed below who con-

tributed to the Guideline by providing comments during

the peer review process. Their reviews do not neces-

sarily imply endorsement of the Guideline.

Peter C. Albertsen, MD

Mark Ball, MD

Michael Blute, MD

Stephen Boorjian, MD

Rodney H. Breau, MD

Anthony Corcoran, MD

Paul Crispen, MD

John D. Denstedt, MD

James A. Eastham, MD

Pat Fox Fulgham, MD

William F. Gee, MD

David Ginsberg, MD

David F. Green, MD

Frederick A. Gulmi, MD

Kammi Henriksen, MD

Stephen Jackman, MD

Michael Jewett, MD

Kenar Jhaveri, MD

Melissa R. Kaufman,MD

Louis R. Kavoussi, MD

Raymond Leveillee, MD

Deborah J. Lightner, MD

Kevin R. Loughlin, MD

Viraj Master, MD

Surena Matin, MD

Patrick Hayes McKenna, MD

Randall B. Meacham, MD

Joshua J. Meeks, MD

Adam Metwalli, MD

Ravi Munver, MD

Gladell Paner, MD

Allan Pantuck, MD

Maria Picken, MD

Glenn M. Preminger, MD

Marcus Quek, MD

Jay Raman, MD

Stephen Riggs, MD

Paul Russo, MD

Arthur Sagalowsky, MD

Steven Salvatore, MD

Stephen J. Savage, MD

Roger E. Schultz, MD

Kirill Shiranov, MD

Marc Smaldone, MD

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer

Angela Smith, MD

Thomas F. Stringer, MD

Stephen Strup, MD

Li-Ming Su, MD

Chandru P. Sundaram, MD

Scott K. Swanson, MD

R. Houston Thompson, MD

Luan Truong, MD

Christopher Weight, MD

J. Stuart Wolf, Jr., MD

DISCLAIMER

This document was written by the Renal Mass Guideline

Amendment Panel of the American Urological Associa-

tion Education and Research, Inc., which was created in

2020. The Practice Guidelines Committee (PGC) of the

AUA selected the committee chair. Panel members were

selected by the chair. Membership of the Panel included

specialists in urology and primary care with specific ex-

pertise on this disorder. The mission of the panel was to

develop recommendations that are analysis based or

consensus-based, depending on panel processes and

available data, for optimal clinical practices in the treat-

ment of early stage testicular cancer. Funding of the

panel was provided by the AUA. Panel members re-

ceived no remuneration for their work. Each member of

the panel provides an ongoing conflict of interest disclo-

sure to the AUA, and the Panel Chair, with the support

of AUA Guidelines staff and the PGC, reviews all disclo-

sures and addresses any potential conflicts per AUA’s

Principles, Policies and Procedures for Managing Con-

flicts of Interest. While these guidelines do not neces-

sarily establish the standard of care, AUA seeks to rec-

ommend and to encourage compliance by practitioners

with current best practices related to the condition be-

ing treated. As medical knowledge expands and tech-

nology advances, the guidelines will change. Today

these evidence-based guidelines statements represent

not absolute mandates but provisional proposals for

treatment under the specific conditions described in

each document. For all these reasons, the guidelines do

not pre-empt physician judgment in individual cases.

Treating physicians must take into account variations in

resources, and patient tolerances, needs, and prefer-

ences. Conformance with any clinical guideline does not

guarantee a successful outcome. The guideline text

may include information or recommendations about

certain drug uses (‘off label‘) that are not approved by

the Food and Drug Administration (FDA), or about med-

ications or substances not subject to the FDA approval

process. AUA urges strict compliance with all govern-

ment regulations and protocols for prescription and use

of these substances. The physician is encouraged to

carefully follow all available prescribing information

about indications, contraindications, precautions and

warnings. These guidelines and best practice state-

ments are not intended to provide legal advice about

use and misuse of these substances. Although guide-

lines are intended to encourage best practices and po-

tentially encompass available technologies with suffi-

cient data as of close of the literature review, they are

necessarily time-limited. Guidelines cannot include

evaluation of all data on emerging technologies or man-

agement, including those that are FDA-approved, which

may immediately come to represent accepted clinical

practices. For this reason, the AUA does not regard

technologies or management which are too new to be

addressed by this guideline as necessarily experimental

or investigational.

American Urological Association (AUA)

Renal Mass and

Localized Renal Cancer