High-Dose-Rate Brachytherapy Combined with External Beam Radiotherapy for Newly Defined Very High-Risk and Regional Prostate Cancer: A 17-Year Single-Institution Experience.

Background: The updated National Comprehensive Cancer Network (NCCN) criteria redefine the very high-risk (VHR) prostate cancer (PC) category, identifying patients with highly aggressive disease. Evidence regarding the outcomes of high-dose-rate brachytherapy (HDR-BT) in these patients, including those with regional disease, is limited. Therefore, the present study focused on analyzing the long-term clinical performance of HDR-BT-based radiotherapy (RT) for patients meeting the NCCN criteria for VHR or regional PC. Methods: A total of 215 patients with VHR (n = 179) or regional disease (n = 36) treated with HDR-BT with external beam RT between 2006 and 2022 were retrospectively reviewed. Recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were assessed using Kaplan-Meier methods, and prognostic factors were analyzed using Cox regression. Results: Recurrence occurred in 19 (8.8%) patients, and 22 (10.2%) died, including 4 PC-specific deaths. The 5-year RFS, CSS, and OS rates were 92.5%, 98.9%, and 96.2%, respectively, and the 8-year rates were 88.5%, 97.8%, and 90.8%, respectively. Multivariate analysis revealed that pre-RT prostate-specific antigen (PSA) > 0.1 ng/mL (HR 3.93; p = 0.010) and cT4 disease (HR 4.49; p = 0.032) were independent predictors of inferior RFS. Grade ≥ 3 genitourinary toxicity was observed in 1.9% of patients, and no Grade ≥ 3 gastrointestinal toxicity occurred. Conclusions: HDR-BT-based RT provides durable disease control and low toxicity in patients with NCCN-defined VHR and regional PC. Pre-RT PSA and T stage may inform risk-adapted treatment strategies. The present findings demonstrate the importance of HDR-BT as an effective component of multimodal therapy for highly aggressive PC.