Effects of Cytoreductive Nephrectomy on Nivolumab Outcomes in Patients with Metastatic Clear Cell Renal Carcinoma: A Retrospective Observational Real-Life Data of Turkish Oncology Group

Abstract Renal cell carcinoma is the fourteenth most common cancer in the world with a male to female ratio of 2:1, and clear cell renal cell carcinoma (ccRCC) is the most common histological subtype. Nivolumab is preferred as subsequent therapy in patients with metastatic ccRCC who show progress after at least one line of anti-vascular endothelial growth factor (anti-VEGF) agents. For several decades, removal of the primary tumor, called cytoreductive nephrectomy, was the cornerstone in the treatment of newly diagnosed metastatic ccRCC. There is limited information about how cytoreductive nephrectomy affects survival outcomes in metastatic ccRCC patients treated with nivolumab. In our study, we aimed to investigate the effect of cytoreductive nephrectomy on nivolumab survival outcomes in metastatic ccRCC patients. Our study included 106 de novo metastatic ccRCC patients with a history of nephrectomy at the time of diagnosis from 20 oncology centers in the Turkish Oncology Group. Multivariate Cox regression analysis was performed to investigate the factors affecting survival in patients receiving nivolumab. The median age of the patients was 60.0 (minimum 18.7-maximum 79.2) years. Eighty-three (78.3%) of the patients had undergone cytoreductive nephrectomy. The median overall survival (OS) of the patients receiving nivolumab was 22.7 months (95% CI 16.1–29.3), and the median time-to-treatment discontinuation (TTD) was 12.0 months (95% CI 8.7–15.3). In the multivariate analysis, cytoreductive nephrectomy (p = 0.011) and the International Metastatic RCC Database Consortium (IMDC) risk score (p = 0.024) were among the significant factors affecting TTD, and the IMDC risk score (p = 0.006) was among the significant factors affecting OS. Our study showed that TTD of nivolumab was longer in metastatic ccRCC patients treated with cytoreductive nephrectomy and progressed after at least one line of anti-VEGF agents.