Abstract
<title>Abstract</title> <p>Background The role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) remains debated, and contemporary real-world evidence with rigorous confounding control is limited. Methods Using the SEER database (17 registries, 2005–2020), we identified 19,974 patients with metastatic (M1) RCC of the kidney (ICD-O-3 C64.9). The exposure was CN versus no surgery; the co-primary outcomes were overall survival (OS) and cancer-specific survival (CSS). Confounding by indication was addressed primarily by inverse-probability weighting using a covariate-balancing propensity score (CBPS), with Fine–Gray competing-risks models and sensitivity analyses (propensity-score matching, entropy balancing, landmark analyses, and the E-value). Results Overall, 7,497 patients (37.5%) underwent CN. After CBPS weighting, CN was associated with improved OS (hazard ratio [HR] 0.44, 95% CI 0.41–0.47) and CSS (HR 0.45, 0.41–0.48; both P < 0.001); median OS was 25 versus 7 months, and the association persisted in a doubly robust model (HR 0.41). CN was associated with a lower hazard of cancer-specific death (subdistribution HR 0.51, 0.48–0.55) but not non-cancer death (0.97; P = 0.814). The benefit was consistent across subgroups, greatest in lower T stages (P-interaction < 0.001), and robust across all sensitivity analyses (E-value 2.91). Conclusions In this contemporary population-based cohort, CN was independently associated with substantially better overall and cancer-specific survival in real-world mRCC, particularly in lower-stage disease, supporting its risk-adapted consideration within multidisciplinary management.</p>