Risk factors of skeletal-related events in patients with bone metastatic castration-resistant prostate cancer undergoing treatment with zoledronate.

ABSTRACT

BACKGROUND: Skeletal-related events (SREs) are related to morbidity and mortality in patients with bone metastatic prostate cancer, and preventive strategies based on patient risk assessment are recommended. However, potentiating factors for SREs in patients with bone metastatic prostate cancer are not well elucidated. METHODS: We analyzed the clinical data from a controlled arm of a clinical trial comparing denosumab with zoledronate in patients with bone metastatic, castration resistant prostate cancer (ClinicalTrial.gov ID NCT00321620) available at Project Data Sphere, a broad-access research platform. The primary endpoint was the first SRE after the inclusion to the trial, and the time to the first SRE was analyzed using Cox proportional hazards model based on patients' baseline characteristics including age, race, ECOG performance status (PS), Gleason score, TNM stage at diagnosis, metastasis pattern, and urine and serum laboratory data. RESULTS: Seven hundred ten patients without documented history of osteopenia or osteoporosis whose data was available in the zoledronate arm of the trial were analyzed. The median age of the patients was 71 years old, the median follow-up was 225 days, and 295 patients (42%) had at least one SRE during this period. The univariate analysis showed that history of SREs, Gleason score ≥ 7, elevated serum alkaline phosphatase (ALP), and high urine N-telopeptide cross-links/creatinine ratio (NTx/Cre) are significant baseline risk factors for SREs. Patients with the characteristics of history of SREs, Gleason score ≥ 7 and elevated serum ALP also showed a significantly higher hazard ratio of SREs in multivariate analysis. CONCLUSIONS: The incidence of SREs in patients with bone metastatic prostate cancer may be higher in those with history of SREs, Gleason ≥ 7, and elevated serum ALP.