To conduct a meta-analysis to provide the latest evidence of nonsurgical local salvage options in the first-line radiotherapy failure setting for localized prostate cancer patients.Recurrence of localized prostate cancer after primary radiotherapy (RT) remains a clinical challenge. There is no consensus on optimal nonsurgical local salvage therapies, which mainly consist of cryotherapy (CRYO), high-intensity focused ultrasound (HIFU), high/low-dose-rate brachytherapy (HDR/LDR), and stereotactic body radiotherapy (SBRT).Our study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We systematically searched PubMed, Web of Science, Cochrane Library and ClinicalTrials.gov up to September 2023 to identify potentially relevant studies. The risk of bias was assessed using the European Association of Urology (EAU) items. Biochemical recurrence-free survival (bRFS) and genitourinary/gastrointestinal toxicities were the outcomes of interest. Pooled rates with 95% confidence intervals (CIs) were evaluated.A total of 99 studies comprising 8440 patients were included. The pooled rate of 1-year biochemical control (BC) was highest for LDR (0.88, 95%CI 0.72-0.95) and lowest for SBRT (0.68, 95%CI 0.49-0.83). The pooled rate of 5-year BC was highest for CRYO (0.52, 95%CI 0.33-0.69) and lowest for HDR (0.23, 95%CI 0.08-0.51). HIFU presented the worst outcome of grade ≥3 genitourinary toxicities (GU3), with a rate of 0.22 (95%CI 0.12-0.3). Conversely, CRYO (0.09, 95%CI 0.04-0.14), HDR (0.05, 95%CI 0.02-0.07), LDR (0.10, 95%CI 0.06-0.14) and SBRT (0.06, 95%CI 0.03-0.09) presented low rates of GU3. All subgroups induced a quite low incidence of grade ≥3 gastrointestinal toxicities (GI3).Nonsurgical salvage therapies are promising modalities for prostate cancer in the local radiorecurrence setting. Based on the preliminary evidence from this study, CRYO and SBRT might present a relatively steady efficacy of BC with acceptable treatment-related toxicities.Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.