The Safety and Efficacy of Targeted Alpha Therapy, Ac-225 Prostate-Specific Membrane Antigen, in Patients With Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis


BEŞİROĞLU H., KADIHASANOĞLU M.

PROSTATE, cilt.85, sa.6, ss.541-557, 2025 (SCI-Expanded, Scopus) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 85 Sayı: 6
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1002/pros.24857
  • Dergi Adı: PROSTATE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Gender Studies Database, Veterinary Science Database
  • Sayfa Sayıları: ss.541-557
  • Anahtar Kelimeler: Actinium-225, meta-analysis, metastatic castration resistance prostate cancer, prostate cancer, prostate-specific membrane antigen-targeted therapy, targeted alpha therapy
  • İstanbul Üniversitesi-Cerrahpaşa Adresli: Evet

Özet

BackgroundMetastatic 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.MethodsWe 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.ResultsThe 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.Conclusions225Ac-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.