Local Salvage Therapy Alone for Local Recurrence of Prostate Cancer After Radiotherapy

Importance: Standard-of-care management of radiorecurrent prostate cancer (PCa) involves systemic therapy; however, some patients seek to avoid the adverse events (AEs) that are associated with androgen-deprivation therapy (ADT). Objective: To determine outcomes of local therapy without systemic therapy for radiorecurrent PCa. Data Sources: MEDLINE, Embase, Web of Science Core Collection, and Google Scholar were searched from inception up to May 2025. No date or language filters were used. Data were analyzed from June to November 2025. Study Selection: Prospective and retrospective studies were selected that investigated local salvage therapies without concomitant systemic treatment for locally recurrent PCa after definitive radiotherapy. Eligible studies provided ADT-free survival (ADT-FS) and/or metastasis-free survival (MFS). Authors were contacted for additional data. Data Extraction and Synthesis: This study was prospectively registered and adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias was assessed using Risk of Bias Assessment Tool for Nonrandomized Studies, version 2. Individual patient data were reconstructed from Kaplan-Meier curves or retrieved from authors. ADT-FS, MFS, and rates of AEs were pooled in a random-effects models. Main Outcomes and Measures: Main outcomes were ADT-FS and MFS, which were modeled as pooled summary Kaplan-Meier curves, and rates of severe or worse AEs, which were modeled as proportions. Outcomes were stratified by treatment method. Results: Thirty-one studies (4525 patients) were identified that assessed salvage high-dose-rate brachytherapy (HDR-BT; 336 patients), low-dose-rate brachytherapy (LDR-BT; 92 patients), stereotactic body radiotherapy (SBRT; 213 patients), radical prostatectomy (sRP; 1476 patients), cryotherapy (1621 patients), high-intensity focused ultrasonography (HIFU; 677 patients), or mixed methods (110 patients). Prospective studies comprised approximately one-fourth of the evidence (1055 patients); however, none were identified for sRP. Pooled 2-year and 5-year ADT-FS (2887 patients) were 76.8% and 55.2%, respectively. Pooled 2-year and 5-year MFS (3425 patients) were 90.4% and 75.2%, respectively. Rates of severe or worse AEs (2308 patients) ranged from 14% for LDR-BT, 13% for sRP, 5% for HDR-BT, 5% for HIFU, 4% for SBRT, and 2% for cryotherapy. Risk of bias concerns primarily regarded patient selection. Limitations included a lack of randomized clinical trials. Conclusions and Relevance: The findings of this systematic review and meta-analysis suggest that local therapies alone have reasonable efficacy in well-selected patients with locally radiorecurrent PCa. ADT-free survival was maintained for more than three-quarters of patients at 2 years and more than half at 5 years. Approximately one in ten experience an early metastatic event. Rates of severe toxic effects were manageable, in particular for salvage HDR-BT, HIFU, SBRT, and cryotherapy.