Trends in bone health agent use and skeletal events in metastatic castration-resistant prostate cancer

Bone health agents (BHAs) prevent symptomatic skeletal events (SSEs) in bone-metastatic castration-resistant prostate cancer (mCRPC). We evaluated contemporary BHA utilization and SSE incidence (2016-2021) compared with a historical cohort (2010-2015), during a period of substantial changes in mCRPC treatment.

Data from 2,115 CRPC patients with bone metastases (Dutch CAPRI-3 registry) were compared to the CAPRI-2 cohort (N = 1,923). Clinical evolution and SSE outcomes were analysed in 1,792 patients receiving life-prolonging drugs (LPDs), categorized by BHA timing relative to the first LPD: no BHA, early BHA (≤4 weeks), or late BHA (>4 weeks).

Compared to the historical cohort (2010-2015), patients in the 2016-2021 cohort were older (75 vs. 73 years), frailer (Charlson Comorbidity Index ≥5: 44% vs. 13%), and received LPDs in metastatic castration-sensitive setting more frequently (35% vs. 0%). BHA utilization dropped from 60% to 28%, with only 8% receiving guideline-recommended timing of BHA initiation. However, the overall SSE incidence declined from 0.26 to 0.21 events/patient-year between cohorts. Early BHA initiation was predominantly reserved for high-risk disease; this group experienced the highest SSE density (0.29) and shortest median SSE-free survival (8.7 vs. 14.6 months; p < 0.001) compared with the group without BHA.

As the mCRPC population becomes older and more pre-treated, guideline-recommended BHA timing remains limited. Although overall skeletal morbidity declined, the high SSE density in high-risk patients underscores the need to identify those patients most likely to benefit from early bone protection.