Phase II study of salvage HDR brachytherapy combined with external beam radiotherapy for isolated prostate bed relapse after radical prostatectomy: preliminary clinical results.

Abstract

Background: Biochemical recurrence after radical prostatectomy is common, and conventional salvage external beam radiotherapy (EBRT) achieves suboptimal control with significant late morbidity. Advances in PSMA PET/CT and multiparametric MRI enable precise detection of isolated prostate bed relapse (IPBR) at low PSA values. High-dose-rate (HDR) brachytherapy offers focal dose escalation with steep gradients, potentially improving control while sparing organs at risk (OARs).

Methods: We conducted a prospective phase I-II study (NCT06982469) of combined salvage high-dose-rate (HDR) brachytherapy followed by external beam radiotherapy (EBRT) for patients with IPBR. HDR was delivered as 19 Gy in two fractions prescribed to the clinical target volume (CTV) with strict organ-at-risk (OAR) constraints. EBRT to the whole prostate bed and elective pelvic lymph nodes followed combined with 6-month ADT. Toxicity was assessed using CTCAE v5.0 and quality of life with EORTC QLQ-PR25.

Results: Sixteen patients were enrolled between 2020 and 2024. Median PSA at salvage was 0.36 ng/mL. After HDR planning, all dosimetric objectives were met. At a median follow-up of 3.7 years (range, 2.3 - 5.2), 15 out of 16 patients (93.8 %) remained biochemically controlled, with no local failures. Grade 2 late urinary toxicity was documented in one case and no grade 3 late toxicites occurred. Patient-reported urinary and bowel domains showed only minor, non-significant changes at 6 months from baseline.

Conclusions: Combined salvage HDR brachytherapy followed by EBRT for PSMA-detected IPBR is feasible, achieves excellent early biochemical control, and preserves quality of life with favorable toxicity. The trial was closed without completing the target size due to slow accrual although these results warrant confirmation in larger multicenter trials.