To date, radio-recurrent prostate cancer (PCa) ranks as the fourth most common urological malignancy when considering the number of men with localized PCa who undergo radiation treatment and subsequently experience a biochemical recurrence. This systematic review aimed to summarize available evidence about the outcomes of local salvage strategies in patients with local PCa recurrence following primary external-beam radiation therapy (EBRT). We conducted a comprehensive bibliographic search on MEDLINE, Scopus, and Web of Science Core Collection databases in October 2023 to identify studies published in the last 20 years evaluating outcomes of local salvage procedures in patients with locally radio-recurrent PCa following EBRT. The meta-analysis was performed using ProMeta 3 software when two or more studies reported the same outcome. The effect size (ES) was estimated using rates reported with its 95% confidence interval (CI). Overall, 28 studies (6 prospective and 22 retrospective) including 1544 patients were included in the review. Two-year recurrence-free survival (RFS) was 84.0% (95% CI: 67.0-93.0%), 69.0% (95% CI: 42.0-87.0%), 58.0% (95% CI: 43.0-71.0%), and 45% (95% CI: 38.0-52.0%), for patients undergoing brachytherapy (BT), EBRT, Cryotherapy and High-Intensity Focused Ultrasound (HIFU), respectively. After salvage prostatectomy, RFS ranged from 75% to 78.5% at a median follow-up ranging from 18 to 35 months. Estimates for severe gastrointestinal toxicity were 2%, 3%, 3%, 4%, and 11% following cryotherapy, BT, HIFU, EBRT, and salvage radical prostatectomy, respectively. In patients who underwent EBRT as primary treatment, prostate salvage re-irradiation through BT or EBRT represents the modality providing the best balance between efficacy and safety. Unfortunately, due to the low level of evidence, strong recommendations regarding the choice of any of these techniques cannot be made.
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