Exploring new frontiers: Outcomes and feasibility of a third radiotherapy course in recurrent prostate cancer

BACKGROUND AND PURPOSE: Re-irradiation is increasingly recognized as a viable and safe treatment option for prostate cancer (PCa) local recurrence. The aim of this study is to present the safety profile, feasibility, and efficacy of a third radiation therapy (RT) course with stereotactic image-guided technique for PCa local relapse through a retrospective analysis of a tertiary centre experience. MATERIALS AND METHODS: Inclusion criteria for the third RT course were as follows: (1) histologically confirmed PCa initial diagnosis; (2) history of two prior courses of RT targeting the prostate gland or the prostate bed; (3) no evidence of greater than grade 2 genitourinary (GU) or gastrointestinal (GI) late events from previous treatments; (4) diagnosis of local recurrence at the restaging imaging in hormone sensitive patients performed after second RT biochemical recurrence. Primary endpoint was incidence of adverse events (AEs) and secondary endpoints included biochemical recurrence-free survival (BRFS) and clinical progression-free survival (CPFS). RESULTS: From 2013 to 2024, 18 and five patients received a third RT course to a radiologicaly-detectable intraprostatic or prostate-bed recurrence, respectively. Androgen deprivation therapy (ADT) was not routinely used and only seven patients received concurrent ADT. Five patients had follow-up of less than 12 months. Of the remaining 18 patients, five were considered disease-free at a median follow-up of 48.5 months. Median BRFS following third RT was 22.6 months in patients with intraprostatic recurrence and 27.0 months in patients with prostate bed recurrence, while median CPFS was 30.9 months and 33.8 months, respectively. Three grade 3 acute GU events, two grade 3 late GU events, one grade 4 late GU event, and one grade 3 late GI event were recorded. No grade 5 events were observed. CONCLUSIONS: This unique series shows that a third RT can be proposed to highly selected patients as a salvage therapy in experienced centers with an acceptable safety profile, potentially prolonging relapse-free survival and ADT-free interval. Further studies are necessary to fully evaluate the most suitable patients population, optimal dose prescription, and dosimetric constraints to organs at risk.