Bone-related Parameters Are the Main Prognostic Factors for Overall Survival in Men With Bone Metastases From Castration-resistant Prostate Cancer

Eur Urol. 2015 Jul;68(1):42-50. doi: 10.1016/j.eururo.2014.10.001. Epub 2014 Oct 29.

Abstract

Background: 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.

Objective: To evaluate the prognostic value of multiple parameters in men with bone metastases due to CRPC using a contemporary dataset.

Design, setting, and participants: 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.

Outcome measures and statistical analysis: We developed multivariate validated Cox proportional hazards models and nomograms to estimate 12-mo and 24-mo survival probabilities and median survival time.

Results and limitations: 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.

Conclusions: Bone-related parameters are strong prognostic variables for overall survival in patients with bone metastases from CRPC.

Patient summary: 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.

Keywords: Bone metastases; Castration-resistant prostate cancer; Nomogram; Prognostic factors; Survival.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Alkaline Phosphatase / blood
  • Bone Density Conservation Agents / therapeutic use
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / secondary*
  • Collagen Type I / urine
  • Denosumab / therapeutic use
  • Diphosphonates / therapeutic use
  • Double-Blind Method
  • Hemoglobins / metabolism
  • Humans
  • Imidazoles / therapeutic use
  • Kallikreins / blood
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Peptides / urine
  • Prognosis
  • Proportional Hazards Models
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms, Castration-Resistant / metabolism
  • Prostatic Neoplasms, Castration-Resistant / mortality
  • Prostatic Neoplasms, Castration-Resistant / pathology*
  • Zoledronic Acid

Substances

  • Bone Density Conservation Agents
  • Collagen Type I
  • Diphosphonates
  • Hemoglobins
  • Imidazoles
  • Peptides
  • collagen type I trimeric cross-linked peptide
  • Denosumab
  • Zoledronic Acid
  • Alkaline Phosphatase
  • Kallikreins
  • kallikrein-related peptidase 3, human
  • Prostate-Specific Antigen