Adjuvant Radiation Therapy or Observation With or Without Early Salvage Radiation Therapy for Men With Node-Positive Prostate Cancer After Surgery and Negative Preoperative Conventional Imaging: A Multicenter Study.

[PURPOSE] Our goals were to assess the survival outcomes of adjuvant radiation therapy (aRT) vs observation with or without early salvage radiation therapy for cN0M0 pN1 prostate cancer (PCa) and to create a model for clinical decision-making.

[MATERIALS AND METHODS] We retrospectively identified 1103 patients with cN0M0 PCa with pN1 PCa after surgery (2000-2021) at 18 referral centers. Kaplan-Meier curves and Cox proportional hazards models were used.

[RESULTS] Overall, 670 patients (61%) had International Society of Urological Pathology (ISUP) 4 to 5, and the median number of positive nodes was 1. On multivariable analyses, ≥ 3 positive nodes (HR, 2.03, 95% CI, 1.22-3.37; = .006) and ISUP 5 (HR, 1.92, 95% CI, 1.15-3.18; = .01) were associated with an increased all-cause mortality. Based on pT stage, ISUP, and positive nodes, a 2 risk categories model was created. In men undergoing observation, 7-year disease-free survival was 27% (95% CI, 20.4-36) for low- to intermediate-risk and 11% (95% CI, 6.7-17) for high-risk patients; aRT had higher overall survival rates in the high-risk group (92%; 95% CI, 87-96 vs observation 84%, 95% CI, 77-90; = .006). In interaction term analyses, aRT confirmed its protective effect on mortality in high-risk patients (HR, 0.28, 95% CI, 0.09-0.84, = .024). Results were comparable when excluding men with PSA persistence.

[CONCLUSIONS] In cN0M0 pN+ PCa, aRT yields a survival benefit compared with observation with or without early salvage radiation therapy only in men with a high-risk disease based on unfavorable prognostic factors. We created a risk model to guide clinical decision-making in this setting.