Upfront Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors or Targeted Therapy: An Observational Study from the International Metastatic Renal Cell Carcinoma Database Consortium

Background: The role of upfront cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) in the era of immune checkpoint inhibitors is unclear. Objective: To evaluate the relationship between upfront CN and clinical outcomes in the setting of mRCC treated with immune checkpoint inhibitors or targeted therapy. Design, setting, and participants: Using the International Metastatic RCC Database Consortium, we retrospectively identified patients diagnosed with de novo mRCC treated with immune checkpoint inhibitors or targeted therapy. Outcome measurements and statistical analysis: Overall survival (OS) was compared between the two groups using the Kaplan-Meier method and multivariable Cox regressions adjusting for known prognostic factors. Results and limitations: We identified a total of 4639 eligible patients with mRCC. Among the 4202 patients treated with targeted therapy and 437 patients treated with immune checkpoint inhibitors, 2326 (55%) and 234 (54%) patients received upfront CN prior to treatment start. In multivariable analyses, CN was associated with significantly better OS in both the immune checkpoint inhibitor–treated (hazard ratio [HR]: 0.61; 95% confidence interval [CI], 0.41–0.90, p = 0.013) and the targeted therapy treatment (HR: 0.72; 95% CI, 0.67–0.78, p < 0.001) group. There was no difference in OS benefit of CN between the immune checkpoint inhibitor and targeted therapy treatment groups (interaction p = 0.6). Limitations include selection of patients from large academic centers and the retrospective nature of the study. Conclusions: Upfront CN is associated with a significant OS benefit in selected patients treated by either immune checkpoint inhibitors or targeted therapy, and still has a role in selected patients in the era of immune checkpoint inhibitors. Patient summary: Before effective systemic therapies were available for metastatic kidney cancer, surgical removal of the primary (kidney) tumor was the mainstay of treatment. The role of removing the primary tumor has recently been called into question given that more effective systemic therapies have become available. In this study, we find that removal of the primary kidney tumor still has a benefit for selected patients treated with highly effective modern systemic therapies, including targeted therapies and immune checkpoint inhibitors.