title: Failure-Free Survival and Radiotherapy in Patients With Newly Diagnosed Nonmetastatic Prostate Cancer: Data From Patients in the Control Arm of the STAMPEDE Trial.
abstract: OBJECTIVE
  The natural history of patients with newly diagnosed high-risk nonmetastatic (M0) prostate cancer receiving hormone therapy (HT) either alone or with standard-of-care radiotherapy (RT) is not well documented. Furthermore, no clinical trial has assessed the role of RT in patients with node-positive (N+) M0 disease. The STAMPEDE Trial includes such individuals, allowing an exploratory multivariate analysis of the impact of radical RT.
  
  
  OBJECTIVE
  To describe survival and the impact on failure-free survival of RT by nodal involvement in these patients.
  
  
  METHODS
  Cohort study using data collected for patients allocated to the control arm (standard-of-care only) of the STAMPEDE Trial between October 5, 2005, and May 1, 2014. Outcomes are presented as hazard ratios (HRs) with 95% CIs derived from adjusted Cox models; survival estimates are reported at 2 and 5 years. Participants were high-risk, hormone-naive patients with newly diagnosed M0 prostate cancer starting long-term HT for the first time. Radiotherapy is encouraged in this group, but mandated for patients with node-negative (N0) M0 disease only since November 2011.
  
  
  METHODS
  Long-term HT either alone or with RT, as per local standard. Planned RT use was recorded at entry.
  
  
  METHODS
  Failure-free survival (FFS) and overall survival.
  
  
  RESULTS
  A total of 721 men with newly diagnosed M0 disease were included: median age at entry, 66 (interquartile range [IQR], 61-72) years, median (IQR) prostate-specific antigen level of 43 (18-88) ng/mL. There were 40 deaths (31 owing to prostate cancer) with 17 months' median follow-up. Two-year survival was 96% (95% CI, 93%-97%) and 2-year FFS, 77% (95% CI, 73%-81%). Median (IQR) FFS was 63 (26 to not reached) months. Time to FFS was worse in patients with N+ disease (HR, 2.02 [95% CI, 1.46-2.81]) than in those with N0 disease. Failure-free survival outcomes favored planned use of RT for patients with both N0M0 (HR, 0.33 [95% CI, 0.18-0.61]) and N+M0 disease (HR, 0.48 [95% CI, 0.29-0.79]).
  
  
  CONCLUSIONS
  Survival for men entering the cohort with high-risk M0 disease was higher than anticipated at study inception. These nonrandomized data were consistent with previous trials that support routine use of RT with HT in patients with N0M0 disease. Additionally, the data suggest that the benefits of RT extend to men with N+M0 disease.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00268476; ISRCTN78818544.
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, United Kingdom2University Hospitals Birmingham NHS Foundation Trust, The Medical School, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: James
authors.affiliation: Medical Research Council Clinical Trials Unit, University College, London, United Kingdom.
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Spears
authors.affiliation: Department of Urology, Christie NHS Foundation Trust, Manchester, United Kingdom.
authors.forename: Noel W
authors.initials: NW
authors.lastname: Clarke
authors.affiliation: Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, United Kingdom.
authors.forename: David P
authors.initials: DP
authors.lastname: Dearnaley
authors.affiliation: Velindre Hospital, Cardiff, United Kingdom.
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Mason
authors.affiliation: Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, United Kingdom.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Parker
authors.affiliation: Medical Research Council Clinical Trials Unit, University College, London, United Kingdom.
authors.forename: Alastair W S
authors.initials: AW
authors.lastname: Ritchie
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: J Martin
authors.initials: JM
authors.lastname: Russell
authors.affiliation: Medical Research Council Clinical Trials Unit, University College, London, United Kingdom.
authors.forename: Francesca
authors.initials: F
authors.lastname: Schiavone
authors.affiliation: Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, United Kingdom.
authors.forename: Gerhardt
authors.initials: G
authors.lastname: Attard
authors.affiliation: Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, United Kingdom.
authors.forename: Johann S
authors.initials: JS
authors.lastname: de Bono
authors.affiliation: Royal Preston Hospital, Preston, United Kingdom.
authors.forename: Alison
authors.initials: A
authors.lastname: Birtle
authors.affiliation: Cantonal Hospital St Gallen, St Gallen, Switzerland.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Engeler
authors.affiliation: Greater Manchester Group, Manchester, United Kingdom.
authors.forename: Tony
authors.initials: T
authors.lastname: Elliott
authors.affiliation: Leeds Beckett University, Leeds, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Matheson
authors.affiliation: Belfast City Hospital, Belfast, United Kingdom.
authors.forename: Joe
authors.initials: J
authors.lastname: O'Sullivan
authors.affiliation: Singleton Hospital, Swansea, United Kingdom.
authors.forename: Delia
authors.initials: D
authors.lastname: Pudney
authors.affiliation: Royal Shrewsbury Hospital, Shrewsbury, United Kingdom.
authors.forename: Narayanan
authors.initials: N
authors.lastname: Srihari
authors.affiliation: Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom.
authors.forename: Jan
authors.initials: J
authors.lastname: Wallace
authors.affiliation: Velindre Hospital, Cardiff, United Kingdom.
authors.forename: Jim
authors.initials: J
authors.lastname: Barber
authors.affiliation: CCO Liverpool Warrington Aintree, Liverpool, United Kingdom.
authors.forename: Isabel
authors.initials: I
authors.lastname: Syndikus
authors.affiliation: Medical Research Council Clinical Trials Unit, University College, London, United Kingdom.
authors.forename: Mahesh K B
authors.initials: MK
authors.lastname: Parmar
authors.affiliation: Medical Research Council Clinical Trials Unit, University College, London, United Kingdom.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Sydes
mesh_terms: D000368:Aged; D019583:Dose Fractionation, Radiation; D006801:Humans; D007610:Kallikreins / Q000097:blood; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy*; D011878:Radiotherapy / Q000009:adverse effects / Q000379:methods; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen