The optimal sequence and combination of radium-223 therapy (Ra-223) for castration-resistant prostate cancer with bone metastasis (mCRPC) remain unclear. This study aimed to explore the prognostic factors after Ra-223 administration and to determine the optimal treatment strategy. We enrolled 64 patients with mCRPC who underwent Ra-223 therapy from June 2016 to July 2022 at a single institution in Japan. Overall survival (OS) and pain progression-free survival (p-PFS), which was proposed as a measure of quality of life (QOL), were analyzed using Cox proportional hazards models and log-rank tests, and between-factor analysis was performed with the Mann–Whitney U (MWU) test. Univariable and multivariable analyses revealed prognostic factors; specifically, early treatment (≤third line), completion of six treatment cycles, low bone scan index (BSI) (<0.61), alkaline phosphatase (ALP) (<140 U/L), prostate-specific antigen (PSA; <22.9 ng/mL), lactate dehydrogenase (LDH; <240 U/L), high hemoglobin (Hb) (≥11.4 g/dL), and prior denosumab use significantly prolonged OS. Low BSI, low ALP, and early Ra-223 treatment also prolonged p-PFS in the log-rank tests. The MWU test showed that high BSI (≥0.61) was associated with high PSA and high ALP and a tendency for Hb to decrease. Late Ra-223 treatment (≥fourth line) was significantly associated with low Hb and high PSA. Early Ra-223 treatment was significantly associated with improved OS, and administering Ra-223 before novel hormonal or anticancer agents may be meaningful.
