INTRODUCTION: A recent randomized trial questioned the role of cytoreductive nephrectomy in clear-cell metastatic renal cell carcinoma (ccmRCC). We reassessed the effect of cytoreductive nephrectomy on survival in a contemporary population-based ccmRCC cohort. PATIENTS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2010-2015), we focused on patients with ccmRCC. The primary endpoint consisted of overall mortality. Univariable and multivariable Cox regression models were applied in the overall cohort and in patients who underwent targeted therapy. Sensitivity analyses included 1:1 propensity score matching, 3- and 6-month landmark analyses, incremental survival benefit analyses, and metastases number and location-based stratifications. RESULTS: Of 4062 patients with ccmRCC, 2241 (55.1%) received targeted therapy; cytoreductive nephrectomy was performed in 2226 (54.8%) patients and 1168 (52.1%) patients in the overall and targeted therapy cohorts, respectively. Cytoreductive nephrectomy was associated with lower overall mortality in the overall cohort (median survival, 30 vs. 9 months; hazard ratio [HR], 0.43; P < .001), as well as in the targeted therapy cohort (median survival, 28 vs. 12 months; HR, 0.49; P < .001). In sensitivity analyses, cytoreductive nephrectomy was associated with lower overall mortality after 1:1 propensity score-matching (HR, 0.49; P < .001), in 3- and 6-month landmark analyses (HR, 0.49; P < .001 and HR, 0.51; P < .001, respectively), in metastases number and location-based stratifications, except for exclusive liver metastases, as well as in all incremental benefit analyses. CONCLUSION: Cytoreductive nephrectomy is associated with better survival in patients with ccmRCC, including those exposed to targeted therapy, after adjustment for multiple potential confounders.
