# 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

## TL;DR

This study shows that combining high-dose-rate brachytherapy with external radiation effectively controls aggressive prostate cancer with minimal side effects.

## Contribution

The study provides long-term evidence for HDR-BT in very high-risk and regional prostate cancer under updated NCCN criteria.

## Key findings

- HDR-BT combined with external beam radiotherapy achieved low recurrence rates and high survival rates in high-risk prostate cancer patients.
- Pre-RT PSA levels above 0.1 ng/mL and cT4 disease were significant predictors of cancer recurrence.
- The treatment was associated with low toxicity, with no serious gastrointestinal side effects observed.

## Abstract

This study investigated the effectiveness of high-dose-rate brachytherapy (HDR-BT) combined with external radiation in controlling very aggressive forms of prostate cancer (PC), including cases with tumor spread to nearby lymph nodes. We analyzed the long-term clinical results of an over 200-patient cohort treated with combined HDR-BT and external beam radiotherapy. This study specifically utilizes the revised NCCN criteria to focus on those classified within the highest-risk categories at our institution. This approach provided strong cancer control for many years, with low recurrence rates and very few serious adverse events. Patients with cancer that had grown outside the prostate or with insufficient pre-HDR-BT prostate-specific antigen level decline were more likely to experience recurrence. By clarifying the significance of HDR-BT in very high-risk PC management, this study informs future research directions focused on mitigating the risk of systemic failure and improving oncological outcomes.

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.