Evaluating Risk Factors Associating With Late Recurrence After Low‐Dose‐Rate Brachytherapy for Prostate Cancer Using Machine Learning

BACKGROUND: The Phoenix definition is widely used to define biochemical recurrence (BCR) after radiation therapy for prostate cancer; however, a definitive definition of cure remains unclear. This study aimed to identify factors associated with late BCR after low-dose-rate brachytherapy (LDR-BT), defined as BCR occurring ≥ 5 years after treatment among patients who remained recurrence-free during the first 5 years, using machine-learning methods. METHODS: We retrospectively analyzed 1419 patients who underwent LDR-BT between 2004 and 2019. Of these, 52 (3.7%) experienced BCR within 5 years, and 244 patients did not have ≥ 5 years of follow-up because of death or loss to follow-up. The remaining 1123 patients were recurrence-free at 5 years and formed the analysis cohort for late BCR (≥ 5 years). Random survival forest (RSF) and survival decision-tree analyses were applied to identify predictive factors, and recurrence-free survival was estimated using the Kaplan-Meier method. RESULTS: The 10-year BCR-free survival rate was 94.8%. RSF identified the 5-year prostate-specific antigen (PSA) value, PSA doubling time (PSA-DT) at 5 years, primary Gleason pattern, and NCCN risk classification as the most important predictors. Optimal cutoff values were 0.93 ng/mL for PSA at 5 years and 5.3 years for PSA-DT. Patients with lower PSA or longer PSA-DT had significantly higher 10-year recurrence-free rates than those at higher risk (97.3% vs. 11.1% and 99.0% vs. 68.1%, respectively; p < 0.001). CONCLUSIONS: PSA level and PSA-DT at 5 years were strong predictors of late BCR after LDR-BT. These findings suggest that follow-up intervals may be safely extended for low-risk patients, thereby reducing the burden of hospital visits and healthcare costs.