Postoperative radiotherapy improves survival in node-positive prostate cancer, particularly in patients receiving androgen deprivation therapy

The optimal adjuvant management of pathologically node-positive (pN1) prostate cancer following radical prostatectomy remains controversial, with conflicting retrospective evidence regarding the survival benefit of postoperative radiotherapy. This study aimed to evaluate the association between postoperative radiotherapy and long-term cancer-specific survival (CSS) and overall survival (OS) in a large population-based cohort. Patients with pN1 prostate adenocarcinoma who underwent radical prostatectomy between 2010 and 2022 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were stratified into radical prostatectomy alone (RP-only) and radical prostatectomy plus postoperative radiotherapy (RP + RT) groups. Propensity score matching (1:1) was performed to balance baseline covariates. Multivariable Cox regression, propensity score–matched analyses, and inverse probability of treatment weighting (IPTW) were used to estimate hazard ratios (HRs) for CSS and OS. Competing risk and subgroup analyses were conducted as sensitivity analyses. A total of 7,250 eligible patients were included, comprising 5,006 in the RP-only group and 2,244 in the RP + RT group. Propensity score matching yielded 1,702 well-balanced pairs. In the matched cohort, postoperative radiotherapy was significantly associated with improved CSS (HR = 0.786, 95% CI: 0.635–0.973, P = 0.027) and OS (HR = 0.770, 95% CI: 0.649–0.915, P = 0.003). These findings were consistent in multivariable Cox regression analyses (CSS: HR = 0.825, P = 0.044; OS: HR = 0.792, P = 0.002). Subgroup analyses demonstrated that the survival benefit was most pronounced in patients receiving concurrent androgen deprivation therapy (CSS: HR = 0.575, 95% CI: 0.456–0.726) and in those with pT4 disease (OS: HR = 0.441, 95% CI: 0.235–0.829). Postoperative radiotherapy is associated with improved cancer-specific and overall survival in patients with pN1 prostate cancer following radical prostatectomy. The benefit appears to be greatest in patients receiving concurrent ADT and those with locally advanced disease. These findings support the use of multimodal adjuvant therapy and suggest that radiotherapy alone may be insufficient in this high-risk population.