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Updated: May 30, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
The Safety and Efficacy of Targeted Alpha Therapy, Ac-225 Prostate-Specific Membrane Antigen, in Patients With
Huseyin Besiroglu1, Mustafa Kadihasanoglu1
1Department of Urology, Istanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Istanbul, Turkey.
Background:
Metastatic castration resistance prostate cancer (mCRPC) is a challenging disease with a significant burden of mortality and morbidity. Most of the patients attain resistance to the available treatments, necessitating further novel therapies in this clinical setting. Actinium 225 (225Ac) prostate-specific membrane antigen (PSMA) radioligand therapy has emerged as a promising option and has been utilized for the last decade. Although a few meta-analyses were performed on the efficacy and safety of 225Ac-PSMA RLT in mCRPC patients, several current studies have been added to the literature since the latest meta-analysis. We aimed to gather all individual studies to perform up-to-date meta-analyses.
Methods:
We searched the literature using Pubmed-Medline, Web of Science, Elsevier-Sceince Direct, and Cochrane-Central databases. The data for any PSA decline, over 50% PSA decline, overall survival (OS), progression-free survival (PFS), and toxicity profile were captured from the studies eligible for meta-analysis. We utilized the random effect model to generate pooled estimates.
Results:
The sixteen eligible studies contained 1102 patients. Sixty-three percent of patients achieved more than 50% PSA decline, while 82% had any PSA decline after the completion of therapy. The pooled mean OS and PFS were 12.72 months (9.52-15.91) and 11.02 months (6.88-15.15), respectively. The most common adverse event was xerostomia, with a pooled proportion of 84%. Grade ≥ 3 anemia, thrombocytopenia, leucopenia, and nephrotoxicity were encountered in 9%, 5%, 4%, and 4% of the patients.
Conclusions:
225Ac-PSMA RLT is an efficacious and safe treatment for mCRPC. Future well-designed randomized controlled studies comparing 225Ac-PSMA RLT with other approved therapeutic options would better comprehend the exact role of this therapy in the treatment sequence of mCRPC.
Insights
Actinium-225 (225Ac) PSMA radioligand therapy shows efficacy in metastatic castration-resistant prostate cancer (mCRPC). This meta-analysis confirms its safety and effectiveness, with significant PSA decline and survival benefits in mCRPC patients.
Area of Science:
- Oncology
- Nuclear Medicine
- Radiopharmaceutical Therapy
Background:
- Metastatic castration-resistant prostate cancer (mCRPC) presents significant mortality and morbidity challenges.
- Treatment resistance necessitates novel therapeutic strategies for mCRPC.
- Actinium-225 (225Ac) prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) has emerged as a promising mCRPC treatment over the past decade.
Purpose of the Study:
- To conduct an up-to-date meta-analysis of individual studies on 225Ac-PSMA RLT in mCRPC.
- To evaluate the efficacy and safety of 225Ac-PSMA RLT based on recent literature.
Main Methods:
- Comprehensive literature search across Pubmed-Medline, Web of Science, Elsevier-Science Direct, and Cochrane-Central databases.
- Data extraction included Prostate-Specific Antigen (PSA) decline, Overall Survival (OS), Progression-Free Survival (PFS), and toxicity profiles.
- Random effect model utilized for generating pooled estimates.
Main Results:
- Sixteen studies with 1102 patients were included.
- 82% of patients experienced any PSA decline, with 63% achieving >50% PSA decline.
- Pooled mean OS was 12.72 months and PFS was 11.02 months. Most common toxicity was xerostomia (84%); Grade ≥3 anemia, thrombocytopenia, leucopenia, and nephrotoxicity occurred in 9%, 5%, 4%, and 4% of patients, respectively.
Conclusions:
- 225Ac-PSMA RLT demonstrates efficacy and a favorable safety profile for mCRPC.
- Further well-designed randomized controlled trials are warranted to define its precise role in mCRPC treatment sequencing.
