Biochemical recurrence after radical prostatectomy and postoperative radiotherapy: current evidence and controversial issues.

Purpose of review: This review explores challenges in managing biochemical recurrence (BCR) after radical prostatectomy and postoperative radiotherapy for prostate cancer (PCa) highlighting gaps in risk stratification, imaging, and emerging therapies, as well as advances in molecular imaging and personalized treatment.

Recent findings: Approximately half of PCa patients experience a second BCR after postoperative radiotherapy. Time to recurrence, PSA kinetics, adverse pathological features (ISUP 4-5, pT3-4, and positive surgical margins), alongside genetic profile, are key factors for risk stratification. Combination of androgen deprivation therapy (ADT) and novel androgen receptor pathway inhibitors (ARPIs) represents an established treatment choice. However, recent findings emphasize the growing role of prostate-specific membrane antigen (PSMA) PET in detecting recurrent disease and guide tailored strategies. Based on early phase II trials and retrospective studies, metastasis-directed therapy (MDT) has demonstrated promising efficacy in oligorecurrent PCa, although further validation is warranted.

Summary: BCR after radical prostatectomy and postoperative radiotherapy represents a challenge in PCa management. Risk stratification is key for guiding the addition of ARPIs to standard ADT. PSMA PET may further refine tailored strategies such as MDT, whose promising efficacy needs further exploration. Ongoing trials will clarify treatment sequencing and patient selection in the evolving paradigm of BCR management.