Kidney Cancer: Acting on Disparities and Intervening for Small Renal Masses

During the morning of the second day of the Society of Urologic Oncology Annual Meeting, Solomon L. Woldu, MD, of UT Southwestern, and Phillip M. Pierorazio, MD, of University of Pennsylvania Medicine, presented on disparities in kidney cancer care and outcomes and appropriate active surveillance in small renal masses, respectively.

Dr. Woldu began by showing how cancer disparities, particularly kidney cancer disparities, is a growing PubMed search in recent years. The known causes of healthcare disparities are numerous, including race, ethnicity, gender, language, religion, economic, insurance, comorbidities, and others. “There are a number of challenges with existing disparity research, and any individual disparity is going to be linked to other disparities,” he said, noting how it is difficult to isolate the cause of disparities. Furthermore, negative studies have a hard time getting published, and while large sample sizes in retrospective cohort analyses lend themselves to large P-values, clinical significance may not be present.

“Okay, so now what,” Dr. Woldu posed, or in other words, how do we get these studies in disparity research into something actionable? “We need to get away from broad generalizations and instead focus on specific clinical scenarios where knowledge of a disparity may be actionable,” he asserted.

There are numerous risk factors for racial disparities in kidney cancer, he continued, categorizing them as non-modifiable (eg, age, genetic predisposition, and gender), modifiable (eg, obesity, smoking, alcohol consumption, exercise, blood pressure, and CKD), and environmental or occupational. Significant differences exist in some of these modifiable risk factors, the most prevalent of which is obesity across race; obesity rates in Black and Hispanic populations are substantially higher than that of White populations in the US, and this problem is getting worse. Data suggests there is a rising rate of kidney cancer for all racial groups, but at a “quicker clip” for Black patients than White patients, perhaps related to obesity or CKD.

Furthermore, there are differences in kidney cancer subtypes among racial groups. Notably, Black patients are 3-to-4 times more likely to be diagnosed with papillary renal cell carcinoma (RCC) than White patients.

Dr. Woldu continued with mention that Black and Hispanic are typically diagnosed 4 to 5 years earlier than White patients, though paradoxically, Black patients are more likely to be diagnosed in a localized stage. Differences in treatment patterns also suggest Black and Hispanic patients have higher rates of non-guideline-based treatment, higher odds of “under treatment,” and lower rates of “over treatment.” Clinical trial enrollment is a well-document disparity, and longstanding data suggests that to this day, Black patients with RCC have lower overall survival (OS) than White patients, even when isolating for age, stage, and tumor subtype.

While these differences are broad generalizations, how do we actually diminish disparities? “As urologists, we need to focus on things we can control and positively impacting the patients in front of us,” he said, highlighting a study performed at UT Southwestern on socioeconomic and demographic disparities in immunotherapy for advanced clear cell RCC. Researchers found that age, comorbidities, education, and income level were predictors of receiving immunotherapy, but the “striking” finding was the Black and Hispanic patients were about 20% less likely to receive immunotherapy.

“By compartmentalizing issues of disparity and cancer outcomes, we might get to more discreet things,” Dr. Woldu concluded. “In this case, to move away from the ‘psychic numbing’ phenomenon, when we see underrepresented minority patients in clinic, we can spend the extra time and counsel them on adjuvant immunotherapy.”

Next to the podium was Dr. Pierorazio to argue when and how to intervene past active surveillance for small renal masses. “We know now with at least 10 years of data that active surveillance is safe and non-inferior for small renal masses,” he began, citing slow growth rates, very low rates of metastatic progression, and the safety of delayed intervention. However, non-operative management is still underutilized in the US. Approximately 60% of surgeons offer active surveillance for small renal masses.

“Interestingly, when stratified by age, life expectancy, or tumor size, the greatest predictor of choice of management is the first urologist patients meet with and what their practice patterns are,” he stated. Data suggests that practices that do more prostate and thyroid cancer active surveillance are more likely to recommend active surveillance for small renal masses. Of the 7 factors that influence a patient’s perception, the most important is a physician’s recommendation.

When it comes to reliable triggers and timing for intervention, growth rate, histology, increasing tumor stage, symptoms, and patient preference are considerations, though tumor size is the most reliable predictor of metastatic potential, Dr. Pierorazio noted, adding that “80% to 90% of masses under 4 cm are either benign or low-grade organ-confined RCC that nobody is ever going to die from.” Metastatic rates are low, with less than 2% for 4 cm tumors and less than 1% for masses under 3 cm. He highlighted a study showing that metastases are rare and are often due to initial screening errors to identify metastases and larger renal masses at presentation. Small renal masses are more likely to develop metastases at 6 to 7 cm and during a period of non-compliance or rapid growth in patients who did not show up for appointments.

Thus, he continued, not only is tumor size the most reliable predictor of metastatic potential, but it is also the best trigger for intervention. In current recommendations, 2 cm masses are at very low-risk for metastases (virtually 0%), 3 to 4 cm masses are at low-risk for metastases (less than 1%), and greater than 4 cm masses are at favorable intermediate-risk (1% to 2%).

Growth rate informs active surveillance, Dr. Pierorazio contended, adding three “provocative” statements: zero growth equals zero risk of metastatic disease, clear cell RCC is more likely to grow quickly (but not always), and elevated growth predicts intervention (but not oncologic outcomes). He showcased data and waterfall plots to support all three statements. Regarding the third statement, he highlighted a Fox Chase Cancer Center dataset showing that fast-growing and slow-growing small renal masses have similar pathologic stage at resection, metastatic recurrence, and OS. Growth rates are predictable on active surveillance, and histology is not necessary to predict growth.

“We also know that delayed intervention is safe, and despite annual tumor growth rate, there is no compromise in pathologic stage, oncologic outcomes, or the nephron-sparing window,” he mentioned. Furthermore, elevated growth does not predict metastatic potential for small renal masses under 4 cm.

Dr. Pierorazio concluded his presentation with arguments and supporting data for 2 other statements related to active surveillance for small renal masses: biopsy informs growth rate expectations and helps avoid unnecessary surgery for benign masses, and illness uncertainty and patient preference are strong predictors of active surveillance choice and durability.