ABSTRACT Objective Treatment outcomes for metastatic renal cell carcinoma (mRCC) have significantly improved with immune checkpoint inhibitors (ICIs); however, optimal treatment strategies remain incompletely defined. This study evaluated treatment outcomes in mRCC patients with intact primary renal tumors, focusing on the survival impact of cytoreductive nephrectomy (CN). Methods We retrospectively analyzed 104 consecutive mRCC patients (2019–2024) treated with immuno‐oncology combinations (IO+IO) or IO plus tyrosine kinase inhibitors (IO+TKI). Surgical timing was classified as upfront CN, deferred CN, or non‐CN. Landmark analyses at 6 and 12 months minimized immortal time bias. Multivariable analyses identified survival predictors. Results IO+IO patients were younger (63 vs. 68 years; p = 0.033) with higher progressive disease rates (31% vs. 2%), but similar objective response rates (50% vs. 47%) compared to IO+TKI. Of 104 patients, 25 underwent upfront CN, 25 deferred CN, and 54 non‐CN. Deferred CN independently predicted improved survival versus non‐CN in multivariable analysis (HR 0.17; 95% CI 0.05–0.57) and 6‐month landmark analysis (HR 0.22; 95% CI 0.06–0.83), but not at the 12‐month landmark, suggesting time‐varying effects. Conclusions IO+IO and IO+TKI demonstrated comparable efficacy with distinct profiles. Deferred CN may improve survival when performed within an optimal therapeutic window in selected patients, emphasizing the importance of treatment timing and response‐adapted selection in the ICI era.
Nemoto et al. (Sun,) studied this question.