BackgroundRadical prostatectomy (RP) may occasionally be performed in patients with metastatic prostate cancer (mPCa). However, the role of lymph node dissection (LND) for such cases is unknown. ObjectiveTo test the contemporary effect of LND at RP on cancer-specific mortality (CSM), overall mortality (OM), and early postoperative outcomes compared with no LND in mPCa patients. Design, setting, and participantsWe identified surgically treated mPCa patients within the Surveillance, Epidemiology, and End Result (SEER) database (2004–2014) and the Nationwide Inpatient Sample (NIS) database (2004–2013). Outcome measurements and statistical analysisIn the SEER-based analyses, Kaplan-Meier plots and multivariable Cox regression models (CRMs) were used after inverse probability of treatment weighting (IPTW) adjustment. In the NIS-based analyses, multivariable logistic regression (MLR) and multivariable Poisson regression (MPR) models were used after IPTW and adjustment for clustering. Results and limitationsWithin the SEER database, 199 (60.3%) of 330 mPCa patients treated with RP underwent LND. After IPTW, multivariable CRMs showed lower CSM (hazard ratio [HR]: 0.52, confidence interval [CI]: 0.31–0.87; p=0.01) and OM (HR: 0.38, CI: 0.24–0.60; p<0.001) rates after LND at RP in patients. Within the NIS database, 1186 (71.3%) of 1663 mPCa patients treated with RP underwent LND. After IPTW, MLR models showed higher rates of transfusions (odds ratio [OR]: 1.54, CI: 1.03–2.30; p=0.03) after LND versus no LND. No difference was observed in overall complications (OR: 1.04, CI: 0.77–1.41, p=0.7). In MPR, LND at RP did not affect the length of stay (OR: 1.05, CI: 0.97–1.14, p=0.2). ConclusionsWe are the first to demonstrate that LND at RP is associated with lower CSM and OM in the setting of mPCa, but not with higher rates of perioperative complications. Patient summaryLymph node dissection might further improve the survival benefit of radical prostatectomy in metastatic prostate cancer patients. In consequence, lymph node dissection at radical prostatectomy should strongly be considered in the metastatic setting.