New studies of renal masses may assist in patient counseling

Feb. 19, 2019

Thorough and informative patient counseling is paramount in the management of small renal masses (SRMs), masses that are ≤ 4 cm in diameter. A study from Mayo Clinic published in the October 2018 issue of European Urology may help improve the effectiveness of patient counseling, affording patients the opportunity to make a more personalized management decision.

Over the last 30 years, the paradigm of renal mass management has evolved dramatically. Although ideas and pursuits of partial nephrectomy for imperative indications have been present for over 100 years, the concept of employing nephron-sparing management strategies such as partial nephrectomy, thermal ablation and active surveillance in the setting of a normal contralateral kidney is rather contemporary, as chronicled by Harry W. Herr, M.D., in the Journal of Urology in 2005.

The last few decades have seen increased adoption of partial nephrectomy, including both open and laparoscopic techniques, thermal ablative procedures and active surveillance by the broader urologic community, largely in response to growing wisdom of the nature and behavior of renal masses. This is especially true of the SRM.

A seminal paper addressing the phenotypic nature of SRMs was authored by Igor Frank, M.D., a urologic surgeon at Mayo Clinic's campus in Rochester, Minnesota. In this study, which was published in the Journal of Urology in 2003, Dr. Frank and colleagues reviewed over 2,700 nephrectomy specimens to better understand how the size of the renal mass correlated with the rates of benign versus malignant pathology.

It was observed that tumors < 1 cm in size were benign in 46.3 percent of cases and tumors between 1 and 4 cm were benign approximately 20 percent of the time; conversely, tumors ≥ 7 cm were rarely benign, as only 6.3 percent of cases demonstrated nonmalignant histology.

Moreover, the authors reported that 81.3 percent of renal cell carcinomas (RCCs) < 5 cm were low grade (nuclear grade 1 or 2) compared with only 8 percent of tumors ≥ 5 cm. Since its publication, this study has been cited nearly 700 times and is the basis for much of the understanding of the nature of SRMs.

In 2003, around the time that Dr. Frank's study was published, the notion of active surveillance was in its infancy. Interestingly, in an editorial comment to Dr. Frank's paper, Eila C. Skinner, M.D., chair of Urology at Stanford University, envisaged a situation where select cohorts of otherwise healthy patients might safely undergo observation or watchful waiting, and went so far as to propose the structuring of a prospective clinical trial that could evaluate the feasibility of such a strategy.

Furthermore, Dr. Skinner poignantly asked the urologic community to consider the following question: "Can we identify those in whom disease might be more aggressive?"

Seeking to build on Dr. Frank's work and help answer the question Dr. Skinner posed, Bimal Bhindi, M.D., a recent graduate of the Urologic Oncology Fellowship at Mayo Clinic, and colleagues published the aforementioned Mayo Clinic study on the probability of aggressive versus indolent histology based on renal tumor size and the implications for surveillance and treatment for patients. Study results were published in European Urology in 2018.

Using Mayo Clinic's institutional nephrectomy registry, which includes over 8,000 patients with renal masses that were managed with surgery, Dr. Bhindi and colleagues reassessed the rates of malignancy relative to tumor size as well as evaluated the rates of aggressive malignancy. After applying inclusion criteria, 2,650 patients were included in the study. Aggressive malignancy was defined by the presence of sarcomatoid elements, necrosis or any of the following histologies of RCC:

  • High-grade clear cell RCC
  • High-grade papillary RCC
  • Collecting duct RCC
  • Translocation-associated RCC
  • Hereditary leiomyomatosis RCC
  • Unclassified RCC
  • Malignant non-RCC tumors

The authors demonstrated that tumors measuring 2 cm, 3 cm and 4 cm carried an estimated 18 percent, 24 percent and 29 percent likelihood of aggressive histology, respectively. An important corollary to this finding was that those tumors classified as indolent or aggressive had corresponding 10-year cancer-specific survivals of 96 percent and 81 percent, respectively. "These numbers may be helpful in the modern era, where we know many indolent RCCs can undergo surveillance," said Dr. Bhindi.

The authors furthered stratified their analysis by gender and found that among men, tumors measuring 2 cm, 3 cm, 4 cm, 7 cm and 10 cm had aggressive cancers in 21 percent, 28 percent, 33 percent, 45 percent and 53 percent of individuals, respectively. In women, rates of aggressive histology for tumors of similar sizes were 13 percent, 17 percent, 21 percent, 31 percent and 39 percent, respectively.

In commenting on these findings, Dr. Bhindi said, "A tumor in a male carries a comparable risk of aggressive histology to that of a tumor that's twice as big in a female. This argues for perhaps using sex-specific estimates and perhaps having different thresholds for surveillance for men versus women."

Active surveillance of SRMs is now a widely accepted management strategy. In fact, the updated guideline for the management of clinically localized renal masses set forth by the American Urological Association in 2017 now recognizes active surveillance as an option for all patients with SRMs. Authors of the guideline advise that this strategy be most strongly considered in individuals with a tumor < 2 cm or in those with an unfavorable comorbidity profile that may negate the potential benefit of active treatment. Dr. Bhindi's findings further support the use of active surveillance in the contemporary management of SRMs.

Despite the growing body of evidence supporting use of more-conservative strategies for incidentally detected SRMs, this approach remains widely underutilized. Paras H. Shah, M.D., a urologic oncology fellow at Mayo Clinic in Rochester, Minnesota, authored a multi-institutional collaboration, published in the Journal of Urology in 2018, that queried the National Cancer Database and identified 52,804 patients diagnosed with a renal mass ≤ 4 cm between 2010 and 2014 in the United States.

Although there was noted to be a 25 percent increase in the utilization of active surveillance over the study period, absolute rates of active surveillance remained low (4.8 percent in 2010 and 6.0 percent in 2014), suggesting underutilization.

Interestingly, the authors noted that during this same time period, there was a significant increase in the rates of robotic renal surgery being performed for SRMs (22.1 percent in 2010 and 39.7 percent in 2014), despite increased understanding of the relatively indolent natural history for many SRMs.

Moreover, a similar and disproportionate increase in robotic surgery relative to active surveillance was observed in patients age 75 and older as well as those with several comorbid conditions ― populations for whom active surveillance is advocated by the current American Urological Association guideline. The study went on to raise the issue of whether the steep increase in robotic partial nephrectomy utilization relative to active surveillance during this time hints that robotic technology may possibly have propagated the continued overtreatment of a tumor type characterized in many instances by a relatively indolent natural history.

There is no substitute for evidence-based patient counseling to foster an environment of shared decision-making between patient and provider. With regard to the decision to pursue a surgical approach or an ablative procedure, or monitor the tumor with an active surveillance strategy, the recent work by Drs. Bhindi and Shah has expanded providers' abilities to better educate patients, provide patients with a context of management strategies employed across the country and enable patients to make more-informed decisions.

For more information

Bhindi B, et al. The probability of aggressive versus indolent histology based on renal tumor size: Implications for surveillance and treatment. European Urology. 2018;74:489.

Dr. Bhindi is a native of Canada and completed his urologic oncology fellowship at the Mayo Clinic in 2018. He is currently in practice at the University of Calgary and the Southern Alberta Institute of Urology, where he is actively seeing patients and continuing his research pursuits.

Herr HW. A history of partial nephrectomy for renal tumors. Journal of Urology. 2005;173:705.

Frank I, et al. Solid renal tumors: An analysis of pathological features related to tumor size. Journal of Urology. 2003;170:2217.

Skinner EC. Editorial comment. Journal of Urology. 2003;170:2220.

Campbell S, et al. Renal mass and localized renal cancer: AUA guideline. Journal of Urology. 2017;198:520.

Shah PH, et al. The temporal association of robotic surgical diffusion with overtreatment of the small renal mass. Journal of Urology. 2018;200:981.

Dr. Shah is from New York and will be completing his urologic oncology fellowship in the summer of 2019. He will be returning to New York where he will join the staff of Albany Medical Center as a urologic oncologist in the fall.