Bone-related Parameters are the Main Prognostic Factors for Overall Survival in Men with Bone Metastases from Castration-resistant Prostate Cancer.

Abstract

Previous studies have reported on prognostic factors for castration-resistant prostate cancer (CRPC); however, most of these studies were conducted before docetaxel chemotherapy was approved for CRPC. To evaluate the prognostic value of multiple parameters in men with bone metastases due to CRPC using a contemporary dataset. The analysis included 1901 patients with metastatic CRPC enrolled in an international, multicenter, randomized, double-blind phase 3 trial conducted between May 2006 and October 2009. We developed multivariate validated Cox proportional hazards models and nomograms to estimate 12-mo and 24-mo survival probabilities and median survival time. The median (95% confidence interval) overall survival was 20 (18, 21) mo. The final model included 12 of the 15 potential prognostic variables evaluated (concordance index 0.72). Seven bone-related variables were associated with longer survival in the final model: alkaline phosphatase ≤143 U/l (p<0.0001); bone-specific alkaline phosphatase (BSAP) <146 U/l (p<0.0001); corrected urinary N-telopeptide (uNTx) ≤50 nmol/mmol (p=0.0008); mild or no pain (Brief Pain Inventory-Short Form [BPI-SF] score ≤4) (p<0.0001); no previous skeletal-related event (SRE; p=0.0002); longer time from initial diagnosis to first bone metastasis (p<0.0001); and longer time from first bone metastasis to randomization (p<0.0001). Other significant predictors of improved survival included prostate-specific antigen (PSA) level <10 ng/ml (p<0.0001), hemoglobin >128g/l (p<0.0001), absence of visceral metastases (p<0.0001), Eastern Co-operative Oncology Group (ECOG) score ≤1 (p=0.017), and younger age (p=0.008). Nomograms were generated based on the parameters included in the final validated models (with/without uNTx and BSAP). One limitation was that lactate dehydrogenase (LDH) levels, a known prognostic factor, were not available in this study. Bone-related parameters are strong prognostic variables for overall survival in patients with bone metastases from CRPC. Survival time is variable in patients with bone metastases from prostate cancer. We found that factors related to bone help to predict how long a patient will live.