The treatment landscape for metastatic hormone-sensitive prostate cancer continues to evolve, with systemic treatment being the mainstay of current treatment. Prognostic and predictive factors such as tumour volume and disease presentation have been studied to assess responses to different treatments. Intensification and de-escalation strategies arouse great interest, so several trials are being developed to further personalize the therapy in these populations. Is there an optimal sequence and a possible option to de-intensify treatment in selected patients with a favourable profile? This and other goals will be the subject of this review.

Local recurrence of prostate cancer following radical prostatectomy (RP) and adjuvant or salvage external beam radiotherapy (a/sEBRT) presents a therapeutic challenge. Salvage high-dose-rate brachytherapy (HDR-BT) is a promising modality, though evidence remains limited. We retrospectively analyzed 90 patients treated with salvage HDR-BT after RP and a/sEBRT across 10 UroGEC-ESTRO-affiliated European centers. Eligible patients had biopsy- or imaging-confirmed local recurrence and ECOG performance status 0-2. Primary endpoints were local recurrence-free survival (LRFS) and toxicity; secondary endpoints included biochemical failure-free survival (BFFS), metastasis-free survival (MFS), progression-free survival (PFS), and overall survival (OS). The median follow-up was 47 months. The 5-year LRFS was 81.1 %, BFFS 62 %, MFS 77.5 %, PFS 58.0 %, and OS 95.9 %. Biopsy-confirmed recurrence and use of androgen deprivation therapy (ADT) were associated with improved LRFS and PFS. Grade ≥3 genitourinary toxicity occurred in 5.5 % (acute) and 8.9 % (late) of patients; gastrointestinal grade 3 toxicity was observed in 1.1 %. HDR-BT is a safe and effective salvage option for well-selected patients with local recurrence after RP and a/sEBRT. Our data support its feasibility, acceptable toxicity, and favorable oncologic outcomes. Biopsy confirmation and ADT use may improve results and should be considered in treatment planning. These findings warrant further prospective evaluation to optimize patient selection and refine salvage strategies.