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Evolving Epidemiologic Trends of Renal Cell Cancer by Histologic Subtype: An Updated Analysis of the California Cancer Registry

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Background: While most renal cell carcinomas (RCC) are of the clear cell subtype, other histologic subtypes are well described and have distinct clinical behavior. This study seeks to evaluate survival of clear and non-clear cell RCC retrospectively from a large, population-based cancer registry. Objectives: The key objectives of this study were to determine cancer-specific survival (CSS) and overall survival (OS) of RCC by histologic subtype and to examine survival by histologic subtype since the advent of anti-angiogenesis therapy in 2006. Methods: Within the California Cancer Registry (CCR), we used multivariable Cox proportional hazards models to assess the association of histologic subtype with CSS and OS, adjusted for sociodemographic and clinical factors. Results: In the CCR, 33,539 RCC patients were diagnosed between 2004 and 2014. The most common subtype, clear cell RCC, comprised 82.6% (n=27,717) of cases. The next most common subtypes were papillary (8.8%, 2,948) and chromophobe (5.2%, 1,759). RCC was more common in men (62.9%, 21,097) compared to women (37.1%, 12,442). Across histologic subtypes, patients with low neighborhood socioeconomic status had lower CSS (HR=1.07, 95% CI 1.02-1.13, p=0.011) and OS (HR=1.14, 95% CI: 1.10-1.19, p<0.001). On multivariate analysis, we observed an interaction between histologic subtype and CSS, finding that patients in the anti-angiogenesis treatment era with clear cell had a significant improvement in CSS (HR: 0.87, 95% CI: 0.82-0.92, p<0.001) as did patients with collecting duct subtype (HR: 0.25, 95% CI: 0.12-0.51, p<0.001), while there were no differences in outcomes over time among patients with chromophobe or papillary subtypes. After 2006, compared to clear cell subtype, patients with chromophobe subtype had a better CSS (HR=0.40, 95% CI: 0.30-0.53, p<0.001), while those with collecting duct carcinomas had a poorer CSS (HR=1.83, 95% CI: 1.29-2.59, p=0.001). Conclusions: In the era following anti-angiogenesis therapy development, patients with chromophobe subtype RCC continue to have a better prognosis compared with clear cell RCC, and patients with collecting duct subtype continue to have a significantly worse prognosis, with more advanced disease at diagnosis. There have been improvements in CSS in patients with clear cell and collecting duct subtypes since the advent of anti-angiogenesis therapy.

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