PURPOSE: High-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy (EBRT) is an effective treatment for patients with high- and very-high-risk prostate cancer. We sought to identify the factors associated with reduced biochemical recurrence rates following HDR-BT. METHODS: A total of 304 patients with high- or very-high-risk prostate cancer who underwent HDR-BT and EBRT were analyzed. EBRT comprised 50 Gy in 25 fractions and HDR-BT comprised 18 Gy in 2 fractions. Biochemical recurrence was defined as an increase in prostate specific antigen (PSA) by ≥2.0 ng/mL from the nadir level. RESULTS: The median follow-up time was 8.2 years (range, 3.4‒13.7 years) after HDR-BT. The 5-year biochemical progression-free survival (bPFS), overall survival, and cause-specific survival rates were 87.4%, 93.3%, and 100%, respectively. In univariate and multivariable analyses, a biologically effective dose (α/β = 1.5) ≥ 240 Gy and androgen deprivation therapy (ADT) were significantly associated with better bPFS (p = 0.020 and 0.007, respectively), whereas pretreatment PSA ≥ 40 ng/mL and Gleason score group 5 were significantly associated with worse bPFS (p = 0.080 and 0.021, respectively). Grade ≥ 3 rectal toxicities occurred in 0.3% of patients and grade ≥ 3 urinary toxicities occurred in 3.4% of patients. CONCLUSION: In patients with high- and very-high-risk prostate cancer treated with EBRT and HDR-BT, dose escalation and ADT were associated with improved tumor control. By comparison, Gleason score group 5 and pretreatment PSA >
40 ng/mL were associated with worse tumor control.