Rationale: Metastatic prostate cancer in the castration-resistant (mCRPC) setting remains challenging to treat. Prostate-specific membrane antigen (PSMA)-targeted alpha therapy (TAT) is emerging as a promising option. We aimed to systematically review the efficacy and safety of PSMA-TAT in patients with prostate cancer. Methods: A comprehensive search of PubMed/MEDLINE and EMBASE databases was conducted up to October 2024, adhering to the PRISMA guidelines. Selected studies were original research articles evaluating the efficacy and/or safety of PSMA-TAT including at least 10 patients. The outcomes measured included any prostate-specific antigen (PSA) response, ≥50% PSA reduction (PSA50), progression-free survival (PFS), overall survival (OS), and adverse events. PSA50 was pooled using a random-effects model, incorporating individual patient data on PSA50 and previous lines of treatment. Results: Eighteen studies involving 1,155 patients met the inclusion criteria. The majority included heavily pre-treated patients. The most commonly employed radiopharmaceutical was [225Ac]Ac-PSMA-617, in 15 studies. The pooled PSA50 response rate was 65% [95% Confidence interval (CI), 57-72%] with a moderate level of heterogeneity (I² = 81.17%, p < 0.001). Pooled response rates in patients who received none, one, and more than one prior line of treatment were 82% (95% CI, 73-90%), 72% (95% CI, 56-85%), and 55% (95% CI, 48-63%), respectively. PFS varied from 3 to 15 months, and OS from 8 to 31 months. Adverse events were predominantly mild (grades 1-2); severe adverse events (≥ grade 3) included anaemia (11%) and thrombocytopenia (6%). Conclusion: PSMA-TAT holds promising efficacy and an acceptable safety profile for treating metastatic prostate cancer. Randomised controlled trials are needed to optimise treatment protocols toward the implementation of PSMA-TAT into clinical practice.
Theranostics. 2025 Feb 20*** epublish ***
Gaia Ninatti, Pietro Scilipoti, Cristiano Pini, Francesco Barletta, Mattia Longoni, Fabrizia Gelardi, Martina Sollini, Giorgio Gandaglia, Mike Sathekge, Francesco Montorsi, Arturo Chiti, Alberto Briganti
Nuclear Medicine Department, IRCCS San Raffaele Hospital, Milan, Italy., Unit of Urology/Division of Oncology, Gianfranco Soldera Prostate Cancer Lab, IRCCS San Raffaele Scientific Institute, Italy., Department of Nuclear Medicine, University of Pretoria & Steve Biko Academic Hospital, Pretoria, South Africa.