Clinicopathological and survival analysis of clinically advanced papillary and chromophobe renal cell carcinoma

Introduction: Clinically, the papillary (pRCC) and chromophobe (chRCC) histologic subtypes of renal cell carcinoma (RCC) are viewed as more indolent compared to the more-common clear cell histology (ccRCC). However, there remain advanced cases of these purportedly less-aggressive histologies that lead to significant mortality. We therefore sought to evaluate outcomes of advanced pRCC and chRCC compared to ccRCC utilizing the National Cancer Database's registry of RCC patients. Materials and methods: A total of 115,365 ccRCC patients, 28,344 pRCC patients, and 11,942 chRCC patients met eligibility criteria. Overall survival (OS) was estimated using the Kaplan-Meier method (median follow-up 3.6 years). OS was compared between stage III and IV ccRCC, pRCC, and chRCC using multivariable Cox proportional hazards model adjusted for clinical and treatment characteristics. Results: A total of 25.7% of ccRCC patients, 14.1% of pRCC patients, and 14.8% of chRCC patients had stage III to IV disease. The 5-year OS for stage III ccRCC, pRCC, and chRCC was 66.9%, 63.6%, and 80.5%, respectively. The 5-year OS for stage IV ccRCC, pRCC and chRCC was 19.7%, 13.3%, and 22.0%, respectively. The hazard of death was significantly higher for stage IV pRCC vs. ccRCC (hazard ratio = 1.29; 95% confidence interval = 1.19, 1.39; P < 0.01) and similar for stage IV chRCC vs. ccRCC (hazard ratio = 1.01; 95% confidence interval = 0.85, 1.21; P = 0.885). Conclusions: pRCC and chRCC are rare but similarly fatal compared to ccRCC when advanced or metastatic. With most clinical trials devoted toward ccRCC, greater efforts to identify aggressive variants and treatment strategies for metastatic pRCC and chRCC are necessary.