Elevated Bone Turnover Markers Predict Poor Survival in Castration-Resistant Prostate Cancer

Background: Elevated markers of bone turnover have been suggested to predict poor survival in patients with castration-resistant prostate cancer (CRPC). The role of these markers in predicting the effectiveness of bone-targeted therapy, however, remains unclear.

Methods: In a prospective evaluation, researchers analyzed the prognostic and predictive value of bone biomarkers in sera from CRPC patients participating in a placebo-controlled phase III trial. The trial involved treatment with docetaxel, with or without the bone-targeted endothelin-A receptor antagonist atrasentan (SWOG S0421). Markers for bone resorption (N-telopeptide and pyridinoline) and formation (C-terminal collagen propeptide and bone alkaline phosphatase) were assayed in pretreatment and serial sera. Cox proportional hazards regression models were used to assess overall survival, adjusted for clinical variables and multiple comparisons.

Results: Analysis of sera from 778 patients showed that elevated baseline levels of each marker were associated with worse survival (P < .001). Increasing marker levels by week nine of therapy also correlated with subsequent poor survival (P < .001). Notably, patients with the highest marker levels (upper 25th percentile for all markers) not only had a poor prognosis but also experienced a survival benefit from atrasentan (HR = 0.33; 95% CI = 0.15 to 0.71; median survival = 13 [atrasentan] vs 5 months [placebo]; P interaction = .005).