The efficacy and safety of 225Ac-PSMA RLT targeted therapy for metastatic castration-resistant prostate cancer: A systematic review and meta-analysis.

Objective: Using radiolabeled prostate-specific membrane antigen (PSMA) ligands for the treatment of metastatic prostate cancer is a promising therapeutic approach. This systematic review and meta-analysis aims to assess the efficacy and safety of actinium-225 (²²⁵Ac)-PSMA radioligand therapy (RLT) for prostate cancer.

Materials and methods: The systematic review and meta-analysis adheres to the preferred reporting items for systematic reviews and meta-analyses (PRISMA). Searches were conducted in databases including PubMed, Web of Science, Medline, CNKI, and VIP, for studies related to ²²⁵Ac-PSMA RLT for prostate cancer from inception until April 2024. The primary endpoint was the therapeutic effect as measured by post-treatment biochemical response evaluation criteria, while secondary endpoints included evaluating overall survival (OS), progression-free survival (PFS), molecular responses.

Results: A total of 17 studies involving 1042 patients were included. The pooled proportion of patients with PSA reduction was 85% (95% confidence interval [CI]: 80%-91%), and the pooled rate of PSA reduction >50% was 66% (95% CI: 58%-75%). The combined values for OS and PFS were 13.79 months (95% CI: 11.11-16.48 months) and 9.67 months (95% CI: 6.99-12.35 months), respectively. The molecular response rate was 71% (95% CI: 56-87%). The most common side effect of ²²⁵Ac-PSMA RLT was xerostomia, accounting for 63.5%. Anemia, leukopenia, thrombocytopenia, and renal toxicity were observed in 54.3%, 30.4%, 31.8%, 32.0%, respectively.

Conclusion: Actinium-225 -PSMA RLT is an effective and safe treatment for metastatic castration-resistant prostate cancer (mCRPC) patients, with a low incidence of treatment-related adverse reactions. Additionally, a history of lutetium-177 (¹⁷⁷Lu) treatment may have an impact on PSA reduction in mCRPC patients.