Angeles Sanchez-Galvez

Prostate cancer (PCa) is a prevalent malignancy in men worldwide, and both androgen deprivation therapy (ADT) and radiotherapy (RT) are key components of its management. However, these treatments significantly affect bone health by inducing bone mineral density (BMD) loss, osteopenia, osteoporosis and increased fracture risk. ADT promotes a high bone turnover state through hormonal suppression and molecular mechanisms involving increased RANKL expression and osteoclast activation. RT generates direct cytotoxic damage and inflammatory changes that compromise bone microarchitecture. Combined ADT + RT exerts synergistic detrimental effects. This narrative review synthesizes the molecular basis, clinical evidence, preventive strategies and emerging technologies related to bone health in men with PCa undergoing ADT and/or RT.

Background/Objectives: Biochemical recurrence (BCR) occurs in 15–40% of men within five years of radical prostatectomy (RP), presenting a major challenge for long-term disease control. While salvage radiotherapy (SRT) and androgen deprivation therapy (ADT) are established post-RP interventions, the optimal integration of ADT with SRT—regarding timing, duration, and patient selection—remains unclear. We aimed to synthesize current clinical evidence on the efficacy and safety of combining ADT with SRT in patients experiencing BCR after RP. Methods: A narrative review was conducted, encompassing retrospective cohort studies, prospective randomized controlled trials (notably RTOG 9601, GETUG-AFU 16, RADICALS-HD, and SPPORT), and meta-analyses. Studies were selected based on relevance to combined ADT + SRT versus SRT alone, with outcomes of interest including biochemical progression-free survival (bPFS), metastasis-free survival (MFS), and overall survival (OS). Trial characteristics, ADT duration (short-term [4–6 months] versus long-term [≥24 months]), radiation scheme, and prostate specific antigen (PSA) thresholds at SRT initiation were extracted and compared. Results: The combination of ADT and SRT represents a promising strategy for the treatment of prostate cancer with BCR after RP. Current evidence supports its benefit in terms of disease control and survival, particularly in high-risk patients. Conclusions: Differences in inclusion criteria, ADT duration, and the heterogeneous quality of the available studies limit the formulation of universal recommendations. Well-designed prospective trials are needed to optimize therapeutic approaches and personalize treatment based on each patient’s risk profile.