High-dose-rate brachytherapy boost with external beam radiotherapy for localized prostate cancer: Long-term outcomes and toxicity in 607 predominantly high-risk patients.

OBJECTIVE: To report long-term outcomes and late toxicity after external beam radiotherapy (EBRT) with single-fraction high-dose-rate brachytherapy boost (HDR-BTB) for localized prostate cancer, examining HDR-BT sequencing and risk stratification. METHODS AND MATERIALS: We retrospectively analyzed 607 (2012-2023) men treated with EBRT (37.5 Gy/15 or 46 Gy/23 fractions) and 15 Gy HDR-BTB, stratified by CPG, NCCN, and ISUP grade. PRIMARY ENDPOINTS: bPFS and MFS; secondary endpoints: OS and PCSS. Late toxicities were graded using CTCAE v5. RESULTS: Median follow-up was 70 months; 73.4% were NCCN high-risk, 67% CPG 4-5. Six-year outcomes: bPFS 94.1%, MFS 94.2%, OS 92.7%, PCSS 98.1%. Increasing ISUP grade was significantly associated with all outcomes (HR 1.3 OS, 3.2 PCSS, 1.7 MFS, 1.6 bPFS). ISUP 5 had the poorest outcomes (6-year: OS 90.3%, PCSS 93.5%, MFS 88.6%, bPFS 85.2%). Six-year bPFS was 99.3% intermediate-unfavorable vs 89.7% high-risk (HR 7; 95% CI 1.7-28.7; p=0.007). Late grade ≥3 GI/GU toxicity: 0.5%/2.1%; urethral stricture 2.5%; pad-requiring incontinence 1.8%. HDR-BT sequencing did not affect outcomes. CONCLUSIONS: 15 Gy HDR-BTB with EBRT provides excellent disease control with low severe late toxicity in this predominantly high-risk cohort. ISUP grade was the strongest prognostic factor. Treatment sequencing did not affect outcomes, supporting scheduling flexibility.