title: Survival with Newly Diagnosed Metastatic Prostate Cancer in the "Docetaxel Era": Data from 917 Patients in the Control Arm of the STAMPEDE Trial (MRC PR08, CRUK/06/019).
abstract: BACKGROUND
  Prostate cancer (PCa) is the second most common disease among men worldwide. It is important to know survival outcomes and prognostic factors for this disease. Recruitment for the largest therapeutic randomised controlled trial in PCa--the Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy: A Multi-Stage Multi-Arm Randomised Controlled Trial (STAMPEDE)--includes men with newly diagnosed metastatic PCa who are commencing long-term androgen deprivation therapy (ADT); the control arm provides valuable data for a prospective cohort.
  
  
  OBJECTIVE
  Describe survival outcomes, along with current treatment standards and factors associated with prognosis, to inform future trial design in this patient group.
  
  
  METHODS
  STAMPEDE trial control arm comprising men newly diagnosed with M1 disease who were recruited between October 2005 and January 2014.
  
  
  METHODS
  Overall survival (OS) and failure-free survival (FFS) were reported by primary disease characteristics using Kaplan-Meier methods. Hazard ratios and 95% confidence intervals (CIs) were derived from multivariate Cox models.
  
  
  CONCLUSIONS
  A cohort of 917 men with newly diagnosed M1 disease was recruited to the control arm in the specified interval. Median follow-up was 20 mo. Median age at randomisation was 66 yr (interquartile range [IQR]: 61-71), and median prostate-specific antigen level was 112 ng/ml (IQR: 34-373). Most men (n=574; 62%) had bone-only metastases, whereas 237 (26%) had both bone and soft tissue metastases; soft tissue metastasis was found mainly in distant lymph nodes. There were 238 deaths, 202 (85%) from PCa. Median FFS was 11 mo; 2-yr FFS was 29% (95% CI, 25-33). Median OS was 42 mo; 2-yr OS was 72% (95% CI, 68-76). Survival time was influenced by performance status, age, Gleason score, and metastases distribution. Median survival after FFS event was 22 mo. Trial eligibility criteria meant men were younger and fitter than general PCa population.
  
  
  CONCLUSIONS
  Survival remains disappointing in men presenting with M1 disease who are started on only long-term ADT, despite active treatments being available at first failure of ADT. Importantly, men with M1 disease now spend the majority of their remaining life in a state of castration-resistant relapse.
  
  
  RESULTS
  Results from this control arm cohort found survival is relatively short and highly influenced by patient age, fitness, and where prostate cancer has spread in the body.
authors.affiliation: University of Warwick, Coventry, UK. Electronic address: N.D.James@warwick.ac.uk.
authors.forename: Nicholas David
authors.initials: ND
authors.lastname: James
authors.affiliation: Medical Research Council Clinical Trials Unit at University College London, London, UK.
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Spears
authors.affiliation: Department of Urology, The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: Noel W
authors.initials: NW
authors.lastname: Clarke
authors.affiliation: Institute of Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, London and Sutton, UK.
authors.forename: David P
authors.initials: DP
authors.lastname: Dearnaley
authors.affiliation: Institute of Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, London and Sutton, UK.
authors.forename: Johann S
authors.initials: JS
authors.lastname: De Bono
authors.affiliation: Queen Alexandra Hospital, Portsmouth, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Gale
authors.affiliation: Hull & East Yorkshire Hospitals NHS Trust, Hull, UK.
authors.forename: John
authors.initials: J
authors.lastname: Hetherington
authors.affiliation: Mount Vernon Hospital, Northwood, Middlesex, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hoskin
authors.affiliation: University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow, UK.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Jones
authors.affiliation: Royal Surrey County Hospital, Guildford, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Laing
authors.affiliation: Velindre Hospital, Cardiff, UK.
authors.forename: Jason F
authors.initials: JF
authors.lastname: Lester
authors.affiliation: Western General Hospital, Edinburgh, UK.
authors.forename: Duncan
authors.initials: D
authors.lastname: McLaren
authors.affiliation: Institute of Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, London and Sutton, UK.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Parker
authors.affiliation: Medical Research Council Clinical Trials Unit at University College London, London, UK.
authors.forename: Mahesh K B
authors.initials: MKB
authors.lastname: Parmar
authors.affiliation: Medical Research Council Clinical Trials Unit at University College London, London, UK.
authors.forename: Alastair W S
authors.initials: AWS
authors.lastname: Ritchie
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
authors.forename: J Martin
authors.initials: JM
authors.lastname: Russell
authors.affiliation: Kantonsspital Graübunden, Chur, Switzerland.
authors.forename: Räto T
authors.initials: RT
authors.lastname: Strebel
authors.affiliation: Department of Urology, University Hospital, Bern, Switzerland.
authors.forename: George N
authors.initials: GN
authors.lastname: Thalmann
authors.affiliation: Velindre Hospital, Cardiff, UK.
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Mason
authors.affiliation: Medical Research Council Clinical Trials Unit at University College London, London, UK.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Sydes
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D015331:Cohort Studies; D018572:Disease-Free Survival; D000077143:Docetaxel; D055088:Early Detection of Cancer / Q000401:mortality; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis / Q000175:diagnosis / Q000473:pathology / Q000628:therapy*; D010809:Physical Fitness; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D012307:Risk Factors; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D043823:Taxoids; D000077143:Docetaxel; D017430:Prostate-Specific Antigen
keywords: Control arm cohort; Hormone-naïve; Metastatic; Natural history; Prognostic factors; Prospective data; Prostate cancer; Survival; Time to progression