Real-world utilization and timing of initiation of bone-targeting agents (BTAs) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223: Results from Princess Margaret Cancer Centre (PM).

Abstract

68 Background: Patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases treated with Radium-223 are at high risk for skeletal-related events (SREs), which contribute substantially to morbidity and mortality. Bone-targeting agents (BTAs), including zoledronic acid (ZA) and denosumab (Dmab), are recommended by guidelines for SRE protection. We examined real-world utilization and timing of BTA initiation in this high-risk population at a high-volume academic center. Methods: We retrospectively reviewed 252 patients with mCRPC and bone metastases treated with Radium-223 at PM between 2015 and 2024. SREs were defined as spinal cord compression, pathological fracture, or bone metastases requiring radiotherapy or surgery. We assessed the timing of BTA initiation relative to SRE onset and Radium-223 initiation. Pre-planned multivariable analyses (MVA) adjusted for age, baseline PSA, ECOG performance status, and prior SRE history. Results: Radium-223 was administered to 252 patients for an average of 5 cycles. Median age was 73.8 years (39.6-93.4) and median PSA was 44.4 ng/mL (0.4-7238). All patients received prior hormonal therapy, 42.9% had prior Docetaxel; 56.3% had SREs before starting Radium-223. BTAs were prescribed in 153 patients (60.7%) for a median duration of 26.4 months (1.2-110.4). While 129 patients (51.2%) initiated BTAs before Radium-223, 54 (21.4%) started BTA therapy after experiencing an SRE BTAs used included ZA (19%), Dmab (38.9%), and both agents in 2.8%. BTA usage increased over time, from 43.3% in 2009-2015 to 71.6% in 2016-2024. After a median follow up of 14.9 months (0.2-81.5), SREs occurred in 177 patients (70.2%), and 129 (51.2%) experienced recurrent SREs despite BTA use. The rate of pathologic fractures was 23.2%. On MVA, prior SRE history (HR 6.83, 3.48-13.40, p < 0.001) was associated with an increased risk of recurrent SREs, while initiation of Dmab (HR 0.28, 0.13-0.62, p < 0.002) or ZA (HR 0.14, 0.06-0.36) p < 0.001) had an overall protective effect. Conclusions: In this real-world cohort at high risk for SREs, BTAs remained under-utilized and were frequently initiated after the onset of SREs, despite guideline recommendations for early SRE prevention. Although BTA utilization has improved over time, many patients continue to experience recurrent SREs despite BTA therapy. These data underscore the importance of earlier BTA initiation and highlight the need for strategies to further reduce SREs.