Impact of radium-223 on bone imaging and biochemical markers with and without bone-modifying agents in bone-metastatic castration-resistant prostate cancer: results from the kyucog-1901 study

BACKGROUND: Radium-223 dichloride (Ra-223) improves survival in men with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases, but its interaction with bone-modifying agents remains unclear. METHODS: The KYUCOG-1901 prospective multicenter study enrolled Japanese men with mCRPC and bone metastases treated with up to six cycles of Ra-223. Serial assessments included bone scan index (BSI), serum bone metabolic markers (BMMs; BAP, P1NP, and TRACP-5b), and bone mineral density (BMD) from baseline (BL) through one year. Clinical outcomes including radiographic progression-free survival (rPFS), time to symptomatic skeletal event and overall survival were assessed by BSI and serum BMMs. RESULTS: BSI remained stable throughout treatment and follow-up. High BL BSI predicted early discontinuation and shorter rPFS, and increases in BSI correlated with worse rPFS. BAP exhibited a transient decline in patients treated with and without bone-modifying agents (BMAs), while TRACP-5b declined in those receiving BMAs. Elevated BAP at BL and BMMs at end of treatment, and increases in P1NP during therapy, were associated with rPFS. Lumbar spine BMD increased modestly over 1 year in both patients treated with and without BMAs, while femoral BMD remained unchanged. CONCLUSION: Ra-223 stabilized skeletal tumor burden, transiently suppressed serum BMMs, and improved lumbar BMD in men with mCRPC. BSI and serum BMMs provided prognostic information, supporting their integration into longitudinal monitoring. These findings highlight the potential of combining Ra-223 with bone-modifying agents to optimize outcomes.