Real-World Outcomes of Radium-223 Therapy in Metastatic Castration-Resistant Prostate Cancer: Predictive Value of PSA Doubling Time and Enzalutamide Continuation.

Abstract

BackgroundRadium-223 dichloride (Ra-223) is an effective treatment for metastatic castration-resistant prostate cancer (mCRPC) with bone metastases. However, predictive factors associated with treatment efficacy remain unclear. This study evaluated prognostic factors associated with the efficacy of Ra-223 and investigated outcomes according to enzalutamide (ENZ) combination patterns.MethodsWe retrospectively analyzed 34 patients with mCRPC treated with Ra-223 between 2016 and 2024. Progression-free survival (PFS) and overall survival (OS) were evaluated according to time to CRPC, pre-treatment prostate-specific antigen (PSA), PSA doubling time (PSADT), metastatic burden, and ENZ treatment patterns. Cutoff values were determined using the Contal-O'Quigley method. This study was approved by the Institutional Review Board of Gunma University (Approval No. 1662).ResultsThe median time to CRPC, pre-treatment PSA level, and PSADT were 17 months, 6.2 ng/mL, and 2.2 months, respectively. Shorter time to CRPC (≤ 19 months), higher pre-treatment PSA (> 2.67 ng/mL), and shorter PSADT (≤ 2 months) were significantly associated with shorter PFS. Patients with ≥ 4 bone metastatic regions had significantly worse OS than those with ≤ 3 regions. Among the ENZ treatment patterns, continuous ENZ administration combined with Ra-223 was associated with significantly longer PFS than discontinuation of ENZ.ConclusionsTime to CRPC, pre-treatment PSA, and PSADT may represent potentially useful candidate markers for identifying patients more likely to benefit from Ra-223 therapy. Continued ENZ administration during Ra-223 therapy was associated with favorable PFS in selected patients; however, this finding should be considered exploratory and requires validation in larger cohorts.