For a study, researchers sought to assess the function of cytoreductive nephrectomy (CN) in mRCC patients, including those undergoing contemporary treatments. From the de-identified national Flatiron Health database, investigators included patients with synchronous mRCC between 2011 and 2020. Systemic therapy alone, CN followed by systemic therapy (up-front CN [uCN]), and systemic therapy followed by CN was the 3 categories they investigated (deferred CN [dCN]). The main endpoint was the median overall survival (mOS) in patients receiving systemic treatment alone vs uCN. Overall survival in patients receiving uCN as opposed to dCN was a secondary endpoint. First-treatment, landmark, and time-varying covariate analyses were done to get around the immortal time bias. To evaluate the impact of treatment on survival, weighted Kaplan-Meier curves, log-rank tests, and Cox proportional hazards regressions were utilized. A total of 1,910 patients with mRCC received systemic therapy in 972 (57%) cases, uCN in 605 (32%) cases, dCN in 142 (8%) cases, and CN alone in 191 (10%) cases, while 433 (23%) patients got immunotherapy-based treatment. In first-treatment, landmark, and time-varying covariate analyses, the adjusted mOS considerably improved in patients getting CN (mOS 26.6 vs 14.6 months, 36.3 vs 21.1 months, and 26.1 vs 12.2 months, respectively). The timing of systemic therapy relative to CN among patients receiving both CN and systemic therapy was not significantly associated with overall survival (HR=1.0, 95% CI 0.76-1.32, P=0.99). Their results suggested that CN plays an oncologic role in a subset of patients with mRCC. The survival benefit for both up-front and postponed CN in patients receiving both CN and systemic therapy was comparable to systemic therapy alone.