title: Improved survival in a cohort of trial participants with metastatic castration-resistant prostate cancer demonstrates the need for updated prognostic nomograms.
abstract: BACKGROUND
  Median overall survival (OS) in men with metastatic castration-resistant prostate cancer (CRPC) was 13-16 mo in the predocetaxel era. Prognostic nomograms for survival estimation in CRPC were constructed prior to the introduction of docetaxel and other novel treatments.
  
  
  OBJECTIVE
  To examine whether prognostic models still accurately reflect survival in a large cohort of trial participants.
  
  
  METHODS
  Survival analysis of 442 men with CRPC sequentially treated in clinical trials at our institution from June 2003 to December 2011.
  
  
  METHODS
  Predicted survival by Halabi and Smaletz nomograms was compared to observed survival. Cox model multivariate analysis (MVA) used variables at referral, including performance status (PS); levels of prostate-specific antigen (PSA), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), haemoglobin (Hb), and albumin; presence of visceral disease, and metastatic disease at diagnosis.
  
  
  CONCLUSIONS
  From point of referral, chemotherapy-naïve patients had a median OS of 30.6 mo (95% confidence interval [CI], 27.6-36.5 mo). In contrast, predicted survival using the Halabi and Smaletz models was 21 and 18 mo, respectively. In these patients, poor PS, lower Hb level, and increasing LDH level were the strongest predictors in the MVA. In patients referred after chemotherapy, survival from referral was 17.5 mo (95% CI, 16.0-19.5 mo) and increasing LDH level and presence of visceral metastases were the strongest predictors of survival. Median OS from diagnosis of CRPC was 40.7 mo in the overall cohort (95% CI, 36.8-44.0 mo). Clinical trial participation was safe, with low mortality rate. This cohort of men participated in phase 1, 2 and 3 trials and expanded access programs; their data may not reflect survival in all CRPC patients.
  
  
  CONCLUSIONS
  Due to the impact of highly effective novel therapies on survival, prognostic nomograms in current use require revalidation regarding their ability to predict survival in CRPC.
authors: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, Downs Road, Sutton, Surrey, UK.
authors: Aurelius
authors: A
authors: Omlin
authors: Carmel
authors: C
authors: Pezaro
authors: Deborah
authors: D
authors: Mukherji
authors: Amy
authors: A
authors: Mulick Cassidy
authors: Shahneen
authors: S
authors: Sandhu
authors: Diletta
authors: D
authors: Bianchini
authors: David
authors: D
authors: Olmos
authors: Roberta
authors: R
authors: Ferraldeschi
authors: Gal
authors: G
authors: Maier
authors: Emilda
authors: E
authors: Thompson
authors: Chris
authors: C
authors: Parker
authors: Gerhardt
authors: G
authors: Attard
authors: Johann
authors: J
authors: de Bono
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002986:Clinical Trials as Topic; D003661:Decision Support Techniques; D004739:England; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007610:Kallikreins / Q000097:blood; D053208:Kaplan-Meier Estimate; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D049451:Nomograms; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D006454:Hemoglobins; D007770:L-Lactate Dehydrogenase; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Castration-resistant prostate cancer; Prognostic factors; Prognostic nomogram; Survival