The Association Between Cytoreductive Nephrectomy and Overall Survival in Metastatic Renal Cell Carcinoma with Primary Tumor Size ≤4 cm

Background It is unknown whether the survival benefit of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) applies to patients with primary tumor size <= 4 cm.Objective To test the association between CN on overall survival (OS) of mRCC patients with primary tumor size <= 4 cm.Design, setting, and participants Within the Surveillance, Epidemiology, and End Results (SEER) database (2006-2018), all mRCC patients with primary tumor size <= 4 cm were identified.Outcome measurements and statistical analysis Propensity score matching (PSM), Kaplan-Meier plots, multivariable Cox regression analyses, and 6-mo landmark analyses addressed OS according to CN status. Sensitivity analyses examined specific populations of special interest: systemic therapy exposed versus na & iuml;ve, clear-cell (ccmRCC) versus non-clear-cell (non-ccmRCC) mRCC histology, historical (2006-2012) versus contemporary (2013-2018), and young (<= 65 yr) versus old (>65 yr) patients.Results and limitations Of 814 patients, 387 (48%) underwent CN. After PSM, the median OS was 44 versus 7 mo (Delta = 37 mo; p < 0.001) in CN versus no-CN patients. CN was associated with higher OS in overall population (multivariable hazard ratio [HR]: 0.30; p < 0.001) as well as in landmark analyses (HR: 0.39; p < 0.001). In all sensitivity analyses, CN was independently associated with higher OS: systemic therapy exposed, HR: 0.38; systemic therapy na & iuml;ve, HR: 0.31; ccmRCC, HR: 0.29; non-ccmRCC, HR: 0.37; historical, HR: 0.31; contemporary, HR: 0.30; young, HR: 0.23; and old, HR: 0.39 (all p < 0.001).Conclusions The current study validates the association between CN and higher OS in patients with primary tumor size <= 4 cm. This association is robust, controlled for immortal time bias, and valid across systemic treatment exposure, histologic subtypes, years of surgery, and patient age.Patient summary In the current study, we tested the association between cytoreductive nephrectomy (CN) and overall survival in patients with metastatic renal cell carcinoma and small primary tumor size. We found a strong association between CN and survival, which persists even after several significant variations in patient and tumor characteristics.