On behalf of the AUA Guidelines Panel: Steven C. Campbell, Robert G. Uzzo, Peter E. Clark, Sam S. Chang, Jose A. Karam and Lesley Souter

Conflict of Interest: Dr. Campbell has no conflict of interest or disclosure regarding this educational activity.

The AUA Guidelines for Renal Mass and Localized Kidney Cancer were revised in 2021, and an update regarding this will be provided at the AUA Plenary Session on May 13, 2022. Dr. Steven Campbell will present this summary on behalf of the panel, which included Robert G. Uzzo, Peter E. Clark, Sam S. Chang, Jose A. Karam and Lesley Souter. The full version of the Guideline is available at https://www.auanet.org/guidelines/guidelines/renal-mass-and-localized-renal-cancer-evaluation-management-and-follow-up and is also presented more concisely in Executive Summaries published by The Journal of Urology®.^1,2 The methodology for this process was rigorous and evidence-based, including a systematic literature review and meta-analysis. Input from related societies and stakeholders involved in the care of this patient population was incorporated, and all recommendations underwent extensive peer review. The 2021 Guideline represents a substantial update of the 2017 Guideline for Renal Mass and Kidney Cancer, and it also incorporates other important changes.

What Is New or Different for 2021−22?

• The literature has been updated to 2021
• Updated risk-based surveillance protocols for patients after intervention are merged into this document—this was a separate Guideline previously
• The indications for genetic counseling have been expanded
• For the first time, the issue of adjuvant therapy has been addressed
• Regarding imaging, magnetic resonance imaging (MRI) with contrast can now be used even in patients with severe chronic kidney disease (CKD) or end-stage renal disease
• The indications for renal mass biopsy (RMB) are now more clearly defined, emphasizing a utility-based approach
• The issue of deciding about radical nephrectomy (RN) vs partial nephrectomy (PN) is now more clearly stated to make the recommendations more granular and useful
• The indications and rationale for active surveillance (AS) are now more granular, and followup on AS is now defined in a more robust manner

The algorithms for evaluation, counseling and intervention are illustrated in figure 1, AS principles and protocols are illustrated in figure 2 and similar specifications for followup after intervention are highlighted in figure 3.

Figure 1. Algorithms for evaluation, counseling and intervention. CBC, complete blood count. CMP, comprehensive metabolic panel. eGFR, estimated glomerular filtration rate. FNA, fine needle aspiration. GFR, glomerular filtration rate. UA, urinalysis.

One important statement in the Guidelines relates to the utilization of RN (fig. 1). This specifies that RN should be considered whenever increased oncologic potential is suggested by increased tumor size, RMB suggesting aggressive grade/histology, and/or imaging features suggesting infiltrative or locally advanced features. In this setting, the Guidelines advise that RN is preferred if all of the following criteria are also met: 1) the tumor is high complexity and PN would be challenging even in experienced hands, 2) the patient does not have preexisting CKD/proteinuria and 3) the patient has a normal contralateral kidney and the new baseline estimated glomerular filtration rate will likely be >45 ml/minute/1.73 m² even if RN is performed. If all these criteria are not met, PN should be considered unless there are overriding concerns about the safety or oncologic efficacy of PN. In general, which patients should undergo RN vs PN has been very controversial, and the European Association of Urology and National Comprehensive Cancer Network^® guidelines leave it up to the surgeon to decide based primarily on whether PN is potentially feasible. The AUA Guidelines are unique in that they provide granular information to help clinicians make solid decisions with the goal of providing RN to patients who really need it while avoiding the overutilization of RN that has been a major concern in the field.

Figure 2. AS principles and protocols. LFT, liver function test. mRCC, metastatic RCC. Rx, management. sCr, serum creatinine. US, ultrasound.

Figure 3. Followup after intervention. CBC, complete blood count. CT, computerized tomography. eGFR, estimated glomerular filtration rate. LDH, lactate dehydrogenase. LFT, liver function test. PE, physical examination. PET, positron emission tomography. SCr, serum creatinine.

Another important development is that MRI with contrast can now be obtained even in patients with severe CKD or end-stage renal disease. The risk of nephrogenic fibrosis with second- and third-generation gadolinium agents is extremely low (essentially nonexistent), and this will represent a real game changer for our daily practices.

The indications for genetic counseling have been expanded, and it is now recognized that >6% of all renal cell carcinoma (RCC) cases are familial. Genetic counseling is now recommended for all patients ≤46 years of age with renal cancer, those with multifocal or bilateral renal masses, or whenever 1) the personal or family history suggests a familial RCC syndrome, 2) there is a first- or second-degree relative with a history of RCC, or a known genetic or clinical diagnosis of a familial renal neoplastic syndrome, even if RCC has not been observed, or 3) whenever the pathology demonstrates histology suggestive of such a syndrome.

The Guidelines now provide recommendations about adjuvant therapy after surgery in high-risk patients, reflecting recent studies suggesting potential benefits of targeted therapies or immune checkpoint inhibitors in certain cohorts of patients. Additional data about this topic are expected in the near future that might further impact patient management.

Regarding thermal ablation (TA), RMB is now recommended prior to TA as a separate procedure. This is preferred over RMB at the time of TA because it will facilitate more rational management.

The Guidelines now recommend consideration of AS for patients with solid masses <2 cm and for those with complex but predominantly cystic renal mass, reflecting a relatively low oncologic risk when observing such patients (fig. 2). For various cohorts of patients on AS, the Guidelines now provide specific recommendations about counseling, intensity of surveillance and potential role for RMB.

Followup after intervention has now been updated and merged into the Guidelines, with detailed recommendations regarding general principles and risk-based protocols for surveillance (fig. 3). Appropriate counseling, laboratory testing, and abdominal and chest imaging are reviewed, and the limited role of bone scans, central nervous system imaging and positron emission tomography scans is discussed. For patients with findings suspicious for metastases, the extent of disease should be defined and the patient should be referred to medical oncology. If isolated or oligometastatic disease is identified, surgical resection or ablative therapies should be considered in select patients. Patients with a new renal primary or local recurrence should undergo thorough metastatic evaluation, and if the disease is isolated to the ipsilateral kidney and/or retroperitoneum, a urologist should be involved in the counseling and surgical resection, or ablative therapies can be considered. For various risk categories, a surveillance schedule is provided, defining the intensity and duration of surveillance (fig. 3).

The Guidelines should prove helpful for urologists in their daily practice for the evaluation, counseling, management and surveillance of patients with renal cancer.