Abstract

To test the hypothesis that cytoreductive nephrectomy (CN) improves overall survival (OS) of patients with synchronous metastatic renal cell carcinoma (mRCC), who subsequently receive targeted therapies (TT). We identified 261 patients who received TT for synchronous mRCC with or without prior CN. To achieve balance in baseline characteristics between groups, we used the inverse probability of treatment weighting (IPTW) method. We conducted OS analyses, including IPTW-adjusted Kaplan-Meier curves, Cox regression models, interaction term, and landmark and sensitivity analyses. Of the 261 patients, 97 (37.2%) received CN and 164 (62.8%) did not. IPTW-adjusted analyses showed a statistically significant OS benefit for patients treated with CN (HR 0.63, 95% CI 0.46-0.83, P=0.0015). While there was no statistically significant difference in OS at 3months (P=0.97), 6months (P=0.67), and 12months (P=0.11) from diagnosis, a benefit for the CN group was noted at 18months (P=0.005) and 24months (P=0.004). On interaction term analyses, the beneficial effect of CN increased with better performance status (P=0.06), in women (P=0.03), and in patients with thrombocytosis (P=0.01). IPTW-adjusted analysis of our patient cohort suggests that CN improves OS of patients with synchronous mRCC treated with TT. On the whole, the survival difference appears after 12months. Specific subgroups may particularly benefit from CN, and these subgroups warrant further investigation in prospective trials.

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