Adjuvant radiation therapy or observation with or without early salvage radiation therapy for men with node positive prostate cancer after surgery and negative pre-operative conventional imaging: A multicenter study

Purpose:To assess the survival outcomes of adjuvant radiation therapy (aRT) versus observation with or without early salvage RT (Obs±esRT) for cN0M0 pN1 PCa and to create a model for clinical decision making.Materials and Methods:We retrospectively identified 1,103 patients with cN0M0 PCa with pN1 PCa after surgery (2000-2021) at 18 referral centers. Kaplan-Meier curves, Cox proportional hazards were used.Results:Overall, 670 (61%) had ISUP 4-5 and the median number of positive nodes was 1. On multivariable analyses, ≥3 positive nodes (HR 2.03,95% CI 1.22-3.37; p=0.006) and ISUP 5 (HR 1.92,95% CI 1.15-3.18; p=0.01) were associated with an increased all-cause mortality. Based on pT stage, ISUP and positive nodes, a two risk categories model was created. In men undergoing observation, seven years disease-free survival was 27% (95%CI 20.4-36) for low-intermediate and 11% (95%CI 6.7-17) for high risk patients; aRT had higher OS rates in the high-risk group (92%;95%CI 87-96 vs observation 84%, 95%CI 77-90; p=0.006). In interaction term analyses aRT confirmed its protective effect on mortality in high risk patients (HR 0.28, 95% CI 0.09-0.84, p=0.024). Results were comparable when excluding men with PSA persistence.Conclusions:In cN0M0 pN+ PCa, aRT yields a survival benefit compared to Obs±esRT 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.