To further determine the efficacy and safety of bipolar androgen therapy (BAT) on patients with metastatic castration-resistant prostate cancer (mCRPC) after progression on abiraterone (ABI) or enzalutamide (ENZA).We systematically searched the Pubmed, Web of Science and ClinicalTrials.gov up to June 2021. Literature review, study selection, and data extraction were conducted by 2 reviewers. Risk of bias was assessed according to the methodology of the European Association of Urology (EAU). A systematic review and pooled analysis were performed. The primary outcomes were PSA50 after BAT and AR-targeted therapy rechallenge, objective response rate (ORR) after BAT, and AEs after BAT. The definition of PSA50 was that participants achieving a PSA decline ≥50% according to Prostate Cancer Working Group (PCWG2) criteria. The ORR determined by determined by Response Evaluation Criteria in Solid Tumors (RECIST) included patients experienced partial response (PR) or complete response (CR).In a total of 74 unique records, 5 studies were eligible for inclusion. Participants who underwent BAT achieved PSA50 of 0.26 (95% CI [0.20, 0.32]) and objective response rate (ORR) of 0.32 (95% CI [0.21, 0.44]). Patients completed BAT proceeded to AR-target therapy (ABI or ENZA) achieved moderate response (PSA50 0.54, 95% CI [0.30, 0.76]). Based on our multiple subgroup analysis, type of post-BAT AR-target therapy had a strong impact on PSA50 of AR-target therapy rechallenge. Most of adverse events (AEs) were low grade.The present study indicated that BAT could induce clinical responses in mCRPC patients after progression on ABI or ENZA, with an acceptable side effects profile. BAT could also be able to restore sensitivity to ABI and ENZA rechallenge in a subset of patients.Copyright © 2021 Elsevier Inc. All rights reserved.