title: Bone-related Parameters are the Main Prognostic Factors for Overall Survival in Men with Bone Metastases from Castration-resistant Prostate Cancer.
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.
  
  
  METHODS
  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.
  
  
  METHODS
  We developed multivariate validated Cox proportional hazards models and nomograms to estimate 12-mo and 24-mo survival probabilities and median survival time.
  
  
  CONCLUSIONS
  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.
  
  
  RESULTS
  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.
authors.affiliation: Institut Gustave Roussy, University of Paris Sud, Villejuif, France. Electronic address: karim.fizazi@igr.fr.
authors.forename: Karim
authors.initials: K
authors.lastname: Fizazi
authors.affiliation: Institut Gustave Roussy, University of Paris Sud, Villejuif, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Massard
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, MA, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Smith
authors.affiliation: Nyack Hospital, Nyack, NY, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Rader
authors.affiliation: Cancer Research UK Experimental Cancer Medicine Centres, Leeds and Sheffield, UK.
authors.forename: Janet
authors.initials: J
authors.lastname: Brown
authors.affiliation: Department of Radiotherapy, Greater Poland Cancer Center and Department of Electroradiology, Medical University, Poznań, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Milecki
authors.affiliation: Carolina Urologic Research Center, Myrtle Beach, SC, USA.
authors.forename: Neal
authors.initials: N
authors.lastname: Shore
authors.affiliation: European Georges Pompidou Hospital, Paris, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Oudard
authors.affiliation: The Urology Center of Colorado, Denver, CO, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Karsh
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Carducci
authors.affiliation: Universitario Pedro Ernesto, Rio De Janeiro, Brazil.
authors.forename: Ronaldo
authors.initials: R
authors.lastname: Damião
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Huei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Ying
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Carsten
authors.initials: C
authors.lastname: Goessl
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary*; D024042:Collagen Type I / Q000652:urine; D000069448:Denosumab / Q000627:therapeutic use; D004164:Diphosphonates / Q000627:therapeutic use; D004311:Double-Blind Method; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007610:Kallikreins / Q000097:blood; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010455:Peptides / Q000652:urine; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D004164:Diphosphonates; D006454:Hemoglobins; D007093:Imidazoles; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D000069448:Denosumab; D000077211:Zoledronic Acid; D000469:Alkaline Phosphatase; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Bone metastases; Castration-resistant prostate cancer; Nomogram; Prognostic factors; Survival