Bone-related parameters are the main prognostic factors for overall survival in men with bone metastases from castration-resistant prostate cancer

Karim Fizazi, Christophe Massard, Matthew Smith, Michael Rader, Janet Brown, Piotr Milecki, Neal Shore, Stephane Oudard, Lawrence Karsh, Michael Carducci, Ronaldo Damiaõ, Huei Wang, Wendy Ying, Carsten Goessl

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Previous studies have reported on prognostic factors for castrationresistant 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 prostatespecific antigen (PSA) level < 10 ng/ml (p < 0.0001), hemoglobin >128 g/l (p < 0.0001), absence of visceral metastases (p < 0.0001), Eastern Co-operativeOncology Group (ECOG) score ≥1 (p = 0.017), and younger age (p = 0.008). Nomograms were generated based on the parameters included in the final validatedmodels (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. #2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Original languageEnglish (US)
Pages (from-to)42-50
Number of pages9
JournalEuropean Urology
Volume68
Issue number1
DOIs
StatePublished - 2015

Keywords

  • Bone metastases
  • Castration-resistant prostate cancer
  • Nomogram
  • Prognostic factors
  • Survival

ASJC Scopus subject areas

  • Urology

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