Managing Small Renal Masses: A Point-by-Point Consideration of ASCO’s Clinical Practice Guideline


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“More than one guideline exists…. Thankfully, all these guidelines are using practically the same data and are providing generally consistent recommendations.”
— Jose A. Karam, MD, FACS

As reviewed in this issue of The ASCO Post, a recent issue of the Journal of Clinical Oncology featured an ASCO Clinical Practice Guideline on the management of small renal masses reported by Finelli and colleagues.1 This comprehensive guideline is written by a group of well-regarded and well-published experts in the field of kidney cancer and follows a rigorous and thorough methodology.

Notably, but not surprisingly, the vast majority of the data behind the recommendations are from individual retrospective series or ­meta-analyses/systematic reviews of such series, with few truly randomized clinical trials. 

While it is important to establish recommendations and guidelines, it should be ­noted that more than one guideline exists—others include guidelines from the American Urological Association,2 the European Association of Urology (which will be updated in 2017),3 and the National Comprehensive Cancer Network,4 to name a few. Thankfully, all these guidelines are using practically the same data, occasionally with overlapping authors, and are providing generally consistent recommendations. But which one should the practicing clinician be most familiar with and use in daily practice? 

Let’s dissect each of the ASCO recommendations:

Renal Tumor Biopsy

“Recommendation 1.0: On the basis of tumor-specific findings and competing risks of mortality, all patients with [a small renal mass] should be considered for renal tumor biopsy when the results may alter management.”

Given the safety and reliability of modern renal tumor biopsy, this is certainly a welcome recommendation, in both the standard settings of suspected lymphoma, metastasis, or infection and patients whose management could change based on renal tumor biopsy result. Caution should be taken to avoid using the finding of a low tumor grade to guide therapy, as grade determination is still not accurate with renal tumor biopsy, partly due to tumor grade heterogeneity. Renal tumor biopsy in patients whose only realistic option is active surveillance should be avoided if possible, as, by definition, it will not change management. 

Active Surveillance

“Recommendation 2.0: Active surveillance should be an initial management option for patients who have significant comorbidities and limited life expectancy.”

Managing Small Renal Masses

Do a biopsy when you need to, do a partial nephrectomy (or ablation) when you can, do a radical nephrectomy when you can’t, do active surveillance when the patient can’t, and refer to a nephrologist when you should.

While this is certainly consistent with all studies and other guidelines, the best objective way to quantify comorbidities and life expectancy is still unclear. For example, what Charlson Comorbidity Index cutoff, if any, should be used to recommend active surveillance? Although the authors suggest using nomograms incorporating comorbidity measures in order to refine selection for active surveillance,5,6 caution should be taken, as these nomograms were based on patients over age 65, and more importantly, all patients already had surgical intervention. 

While these nomograms are potentially helpful in patients who already had surgery, applying them in cases of an untreated tumor is inaccurate and misleading. Similar work is needed in patients on active surveillance, which can be done ideally by pooling data from multiple centers with large prospective active surveillance registries. As far as life expectancy is concerned, what life tables/tools does the ASCO panel suggest for this assessment, and how do these life tables differ in terms of the geographic, educational, demographic, and socioeconomic status of the patient?

Partial Nephrectomy

“Recommendation 3.1: Partial nephrectomy for [small renal masses] is the standard treatment that should be offered to all patients for whom an intervention is indicated and who possess a tumor that is amenable to this approach.”

This recommendation is consistent with other guidelines and results in little controversy, although it is based purely on retrospective data. 

Percutaneous Thermal Ablation

“Recommendation 3.2: Percutaneous thermal ablation should be considered an option for patients who possess tumors such that complete ablation will be achieved. A biopsy should be obtained before or at the time of ablation.”

In the current guidelines, this recommendation appears to be purely based on anatomic/technical features and differs from both the American Urological Association and the European Association of Urology guidelines, where ablation is generally recommended for high-risk surgical candidates, including elderly or comorbid patients (arguably the same population that active surveillance can be offered to). This is certainly an interesting recommendation given the paucity of studies and long-term data with ablation therapy, especially in the “healthy” patient population.

Radical Nephrectomy

“Recommendation 3.3: Radical nephrectomy for [small renal masses] should be reserved only for patients who possess a tumor of significant complexity that is not amenable to partial nephrectomy or where partial nephrectomy may result in unacceptable morbidity even when performed at centers with expertise.” 

There is consensus here among the guidelines, which does not come as a surprise. This might be a group of patients in whom doing a biopsy could change management, as a benign finding on biopsy could avoid potential end-stage renal disease, among other possible complications.

As ASCO has been encouraging and endorsing clinical trials as vital to patient care in recently published guidelines, two potential trials (with appropriate stratification factors and endpoints) come to mind in the setting of small renal masses: A randomized trial of ablation therapy vs active surveillance in patients with significant comorbidities and a randomized trial of partial nephrectomy vs ablation (in masses amenable to both) in “healthy” patients. Admittedly, the latter trial concept has proven difficult to study: The CONSERVE trial in the UK (clinicaltrials.gov NCT01608165) was terminated early due to poor accrual. However, an ongoing prospective clinical trial in China (clinicaltrials.gov NCT03094949) is comparing microwave ablation with partial nephrectomy in a nonrandomized fashion, with results pending hopefully in 2017 or 2018.  A randomized trial of partial nephrectomy vs radical nephrectomy for a small renal mass seems to have lost its equipoise and is unlikely to be conducted again.

To simplistically summarize the management of small renal masses per the ASCO guidelines: Do a biopsy if you need to, do a partial nephrectomy (or ablation) when you can, do a radical nephrectomy when you can’t, do active surveillance when the patient can’t, and refer to a nephrologist when you should. 

Disclosure: Dr. Karam is a consultant for and on the advisory board for Pfizer, EMD Serono, and Novartis.

References

1. Finelli A, Ismaila N, Bro B, et al: Management of small renal masses: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 35:668-680, 2017. 

2. Campbell SC, Novick AC, Belldegrun A, et al: Guideline for management of the clinical T1 renal mass. J Urol 182:1271-1279, 2009.

3. Ljungberg B, Bensalah K, Canfield S, et al: EAU guidelines on renal cell carcinoma: The 2014 update. Eur Urol 67:913-924, 2015.

4. NCCN Clinical Practice Guidelines in Oncology: Kidney cancer, version 2.2017. Available at www.nccn.org/professionals/physician_gls/pdf/kidney.pdf. Accessed May 15, 2017.

5. Kutikov A, Egleston BL, Wong YN, et al: Evaluating overall survival and competing risks of death in patients with localized renal cell carcinoma using a comprehensive nomogram. J Clin Oncol 28: 311-317, 2010.

6. Kutikov A, Egleston BL, Canter D, et al: Competing risks of death in patients with localized renal cell carcinoma. J Urol 188:2077-2083, 2012. 


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