Effects of 225Ac-labeled prostate-specific membrane antigen radioligand therapy in metastatic castration-resistant prostate cancer: A meta-analysis.

Prostate-specific membrane antigen (PSMA), overexpressed in prostate cancer, has become a popular target for radionuclide-based theranostic applications in the advanced stages of prostate cancer. We conducted a meta-analysis of the therapeutic effects of PSMA-targeting alpha therapy [225Ac-PSMA radioligand therapy (RLT)] in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: A systematic search was performed using the keywords "mCRPC," "225Ac-PSMA," and "alpha therapy". Therapeutic responses were analyzed as the pooled proportions of patients with more than 50% of prostate-specific antigen (PSA) decline and any PSA decline. Survival outcomes were analyzed by estimating summary survival curves for progression-free survival (PFS) and overall survival (OS). Adverse events were analyzed as the pooled proportions of patients with xerostomia and severe hematotoxicity (anemia, leukocytopenia, and thrombocytopenia). Results: Nine studies with 263 patients were included in our meta-analysis. The pooled proportions of patients with more than 50% of PSA decline and any PSA decline were 60.99% [95% confidence interval (CI) = 54.92-66.83%] and 83.57% (95% CI = 78.62-87.77%), respectively. The estimated mean PFS and mean OS were 9.15 months (95% CI = 6.69-11.03 months) and 11.77 months (95% CI = 9.51-13.49 months), respectively. The pooled proportions of patients with adverse events were 62.81% (95% CI = 39.34-83.46%) for xerostomia, 14.39% (95% CI = 7.76-22.63%) for anemia, 4.12% (95% CI = 0.97-9.31%) for leukocytopenia, and 7.18% (95% CI = 2.70-13.57%) for thrombocytopenia. Conclusion: In our study, around 61% of patients had more than 50% of PSA decline and 84% of patients had any PSA decline after 225Ac-PSMA RLT. The common adverse events in 225Ac-PSMA RLT were xerostomia in 63% of patients and severe hematotoxicity in 4-14% of patients.