AUA 2019: Management Paradigms for Advanced nccRCC in the Modern Era

Chicago, IL USA (UroToday.com) Non-clear cell renal cell carcinoma (nccRCC) is a less common and heterogeneous group of renal malignancies that are driven by unique mutational events as compared to clear cell renal cell carcinoma (ccRCC). The treatment for nccRCC, however, has mirrored the typical treatment paradigms for ccRCC and the survival for these uncommon tumors remains relatively poor, with a generally worse prognosis with ccRCC. nccRCC subtypes include papillary RCC, Chromophobe RCC, Renal Medullary RCC, Mucinous Tubular and Spindle Cell RCC, Xp11 Translocation RCC, and Unclassified RCC.

Dr. Nancy Davis, a medical oncologist from Vanderbilt University in Nashville, TN presented about the past and future of the treatment of nccRCC at the 2019 American Urologic Association Annual Meeting in Chicago, IL. She began by noting that historically, immunotherapy with high dose Interleukin-2 (IL-2) or interferon-alpha (IFN-a) treatment was the only potentially curative therapy in patients but came with severe side-effects. There were no randomized-controlled studies in nccRCC at the time. Next, chemotherapy was attempted in this disease state, but single agent activity was found to be low. There is a niche for chemotherapy, however in sarcomatoid and collecting duct variants of nccRCC.

In the early 2000’s we began to understand more clearly about the pathogenesis which lead to the development of small molecule-targeted inhibitors of VEGF, VEGFR, PDGFR, mTOR, and HIF-1a. Studies involving these drugs were most commonly done in ccRCC, however some nccRCC patients were enrolled in these trials to evaluate efficacy. These trials included ASPEN, ESPN, SWOG1107, RAPTOR, and NCT02127710. More recently, the development of immune checkpoint inhibitors has lead to several trials which allow nccRCC patients to be enrolled to evaluate efficacy, most of which continue to accrue. She hopes that these will lead to more standardized treatment regimens for nccRCC, which has typically mimicked the treatment for ccRCC.

Dr. Davis concluded that in the modern era, patients with nccRCC should be considered for enrollment into clinical trials so that we can obtain valuable outcome information. There are other treatment options, however, including MET inhibitors for papillary RCC. She stresses that patients with nccRCC should be considered for germline testing to evaluate for any actionable mutations.

Presented by: Nancy Davis, MD, Vanderbilt University Medical Center, Nashville, TN

Written by: Brian Kadow, MD. Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Philadelphia, PA. @btkmduro at the American Urological Association's 2019 Annual Meeting (AUA 2019), May 3 – 6, 2019 in Chicago, Illinois