title: Active monitoring, radical prostatectomy, or radiotherapy for localised prostate cancer: study design and diagnostic and baseline results of the ProtecT randomised phase 3 trial.
abstract: BACKGROUND
  Prostate cancer is a major public health problem with considerable uncertainties about the effectiveness of population screening and treatment options. We report the study design, participant sociodemographic and clinical characteristics, and the initial results of the testing and diagnostic phase of the Prostate testing for cancer and Treatment (ProtecT) trial, which aims to investigate the effectiveness of treatments for localised prostate cancer.
  
  
  METHODS
  In this randomised phase 3 trial, men aged 50-69 years registered at 337 primary care centres in nine UK cities were invited to attend a specialist nurse appointment for a serum prostate-specific antigen (PSA) test. Prostate biopsies were offered to men with a PSA concentration of 3·0 μg/L or higher. Consenting participants with clinically localised prostate cancer were randomly assigned to active monitoring (surveillance strategy), radical prostatectomy, or three-dimensional conformal external-beam radiotherapy by a computer-generated allocation system. Randomisation was stratified by site (minimised for differences in participant age, PSA results, and Gleason score). The primary endpoint is prostate cancer mortality at a median 10-year follow-up, ascertained by an independent committee, which will be analysed by intention to treat in 2016. This trial is registered with ClinicalTrials.gov, number NCT02044172, and as an International Standard Randomised Controlled Trial, number ISRCTN20141297.
  
  
  RESULTS
  Between Oct 1, 2001, and Jan 20, 2009, 228,966 men were invited to attend an appointment with a specialist nurse. Of the invited men, 100,444 (44%) attended their initial appointment and 82,429 (82%) of attenders had a PSA test. PSA concentration was below the biopsy threshold in 73,538 (89%) men. Of the 8566 men with a PSA concentration of 3·0-19·9 μg/L, 7414 (87%) underwent biopsies. 2896 men were diagnosed with prostate cancer (4% of tested men and 39% of those who had a biopsy), of whom 2417 (83%) had clinically localised disease (mostly T1c, Gleason score 6). With the addition of 247 pilot study participants recruited between 1999 and 2001, 2664 men were eligible for the treatment trial and 1643 (62%) agreed to be randomly assigned (545 to active monitoring, 545 to radiotherapy, and 553 to radical prostatectomy). Clinical and sociodemographic characteristics of randomly assigned participants were balanced across treatment groups.
  
  
  CONCLUSIONS
  The ProtecT trial randomly assigned 1643 men with localised prostate cancer to active monitoring, radiotherapy, or surgery. Participant clinicopathological features are more consistent with contemporary patient characteristics than in previous prostate cancer treatment trials.
  
  
  BACKGROUND
  UK National Institute for Health Research Health Technology Assessment Programme.
authors.affiliation: University of Bristol, Bristol, UK.
authors.forename: J Athene
authors.initials: JA
authors.lastname: Lane
authors.affiliation: University of Bristol, Bristol, UK.
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Donovan
authors.affiliation: University of Bristol, Bristol, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Davis
authors.affiliation: University of Bristol, Bristol, UK.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Walsh
authors.affiliation: University of Bristol, Bristol, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Dedman
authors.affiliation: University of Bristol, Bristol, UK.
authors.forename: Liz
authors.initials: L
authors.lastname: Down
authors.affiliation: University of Bristol, Bristol, UK.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Turner
authors.affiliation: Cardiff University, Cardiff, UK.
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Mason
authors.affiliation: University of Bristol, Bristol, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Metcalfe
authors.affiliation: University of Bristol, Bristol, UK.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Peters
authors.forename: Richard M
authors.initials: RM
authors.lastname: Martin
authors.affiliation: Cambridge University and Cambridge University Hospitals NHS Trust, Cambridge, UK.
authors.forename: David E
authors.initials: DE
authors.lastname: Neal
authors.affiliation: Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK. Electronic address: freddie.hamdy@nds.ox.ac.uk.
authors.forename: Freddie C
authors.initials: FC
authors.lastname: Hamdy
mesh_terms: D000368:Aged; D001707:Biopsy, Needle; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology*; D018579:Patient Selection; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy / Q000379:methods* / Q000401:mortality; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D020266:Radiotherapy, Conformal / Q000379:methods* / Q000401:mortality; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome; D006113:United Kingdom; D057832:Watchful Waiting / Q000379:methods*
chemical_list: D017430:Prostate-Specific Antigen