Introduction:

While immunotherapy has become first line therapy for metastatic renal cell carcinoma (mRCC) of clear cell (ccRCC) and non-clear cell (nccRCC) histology, in the setting of high-risk localized RCC, nccRCC has been sparsely investigated for adjuvant therapy. We sought to compare outcomes of high risk localized ccRCC and nccRCC.

Methods:

Prospectively collected data from a multicenter database, including University of California San Diego Health (USA), IRCCS San Raffaele Hospital (Italy), Emory University Hospital (USA) and Tokyo Medical and Dental University (Japan), were retrospectively analyzed. A total of 6014 non-metastatic patients treated with radical or partial nephrectomy were included. The cohort was divided between ncc and ccRCC groups for descriptive and survival analyses. Kaplan-Meier analyses (KMA), Log-rank test and Cox regression analyses (Cox) were conducted to evaluate for cancer-specific survival (CSS) and overall survival (OS) and predictors of cancer-specific mortality (CSM) and all-cause mortality (ACM).

Results:

With a median follow-up of 61 months, 4759 patients with ccRCC, 932 papillary, 241 chromophobe, and 82 variant-histology RCCs were analyzed. KMA comparing nccRCC high-grade (G3-G4) tumors and ccRCC high-grade (HG) tumors showed no difference in 5-year CSS rates (nccRCC-HG 91% vs ccRCC-HG 88%, p=0.08) and 5-year OS (nccRCC-HG 79% vs ccRCC-HG, p=0.1). KMA also demonstrated comparable 5-year CSS in patients with nccRCC and positive lymph-nodes (nccRCC-N1) versus ccRCC-N1 (nccRCC-N1 50% vs. ccRCC-N1 52%, p=0.07) and 5-year OS (nccRCC-N1 38% vs ccRCC-N1 37%, p=0.6). Comparing T3 stage tumors between nccRCC and ccRCC, KMA also showed similar 5-year CSS (nccRCC-T3 83% vs. ccRCC-T3 84%, p=0.05) and 5-year OS (nccRCC-T3 73% vs ccRCC-T3 73%, p=0.2). Cox regression for predictors of mortality showed that histology was not an independent predictor of CSM (p=0.17) and ACM (p=0.11).

Conclusion:

While focus of most RCC adjuvant therapy clinical trials has been on ccRCC, aggressive features in nccRCC patients yield similar 5-year cancer-specific and overall survival rates. This study highlights the need for further clinical trials to evaluate efficacy of adjuvant systemic therapy in the setting of unfavourable groups of non-clear cell RCC.

Funding: N/A