title: Mortality Among Men with Advanced Prostate Cancer Excluded from the ProtecT Trial.
abstract: Early detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PCa) may improve survival rates.
  
  
  
  To determine outcomes for men diagnosed with advanced PCa following prostate-specific antigen (PSA) testing who were excluded from the ProtecT randomised trial.
  
  
  
  Mortality was compared for 492 men followed up for a median of 7.4 yr to a contemporaneous cohort of men from the UK Anglia Cancer Network (ACN) and with a matched subset from the ACN.
  
  
  
  PCa-specific and all-cause mortality were compared using Kaplan-Meier analysis and Cox's proportional hazards regression.
  
  
  
  Of the 492 men excluded from the ProtecT cohort, 37 (8%) had metastases (N1, M0=5, M1=32) and 305 had locally advanced disease (62%). The median PSA was 17μg/l. Treatments included radical prostatectomy (RP; n=54; 11%), radiotherapy (RT; n=245; 50%), androgen deprivation therapy (ADT; n=122; 25%), other treatments (n=11; 2%), and unknown (n=60; 12%). There were 49 PCa-specific deaths (10%), of whom 14 men had received radical treatment (5%); and 129 all-cause deaths (26%). In matched ProtecT and ACN cohorts, 37 (9%) and 64 (16%), respectively, died of PCa, while 89 (22%) and 103 (26%) died of all causes. ProtecT men had a 45% lower risk of death from PCa compared to matched cases (hazard ratio 0.55, 95% confidence interval 0.38-0.83; p=0.0037), but mortality was similar in those treated radically. The nonrandomised design is a limitation.
  
  
  
  Men with PSA-detected advanced PCa excluded from ProtecT and treated radically had low rates of PCa death at 7.4-yr follow-up. Among men who underwent nonradical treatment, the ProtecT group had a lower rate of PCa death. Early detection through PSA testing, leadtime bias, and group heterogeneity are possible factors in this finding.
  
  
  
  Prostate cancer that has spread outside the prostate gland without causing symptoms can be detected via prostate-specific antigen testing and treated, leading to low rates of death from this disease.
authors.affiliation: Academic Urology Group, University of Cambridge, Cambridge, UK. Electronic address: thomasjohnston1@nhs.net.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Johnston
authors.affiliation: Academic Urology Group, University of Cambridge, Cambridge, UK; Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge, UK.
authors.forename: Greg L
authors.initials: GL
authors.lastname: Shaw
authors.affiliation: Academic Urology Group, University of Cambridge, Cambridge, UK; Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge, UK.
authors.forename: Alastair D
authors.initials: AD
authors.lastname: Lamb
authors.affiliation: Statistics and Epidemiology Unit & Cancer Research Centre, University of Warwick, Coventry, UK.
authors.forename: Deepak
authors.initials: D
authors.lastname: Parashar
authors.affiliation: National Cancer Registration Service - Eastern Office, Public Health England, Cambridge, UK.
authors.forename: David
authors.initials: D
authors.lastname: Greenberg
authors.affiliation: Academic Urology Group, University of Cambridge, Cambridge, UK.
authors.forename: Tengbin
authors.initials: T
authors.lastname: Xiong
authors.affiliation: Academic Urology Group, University of Cambridge, Cambridge, UK.
authors.forename: Alison L
authors.initials: AL
authors.lastname: Edwards
authors.affiliation: Academic Urology Group, University of Cambridge, Cambridge, UK.
authors.forename: Vincent
authors.initials: V
authors.lastname: Gnanapragasam
authors.affiliation: Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Holding
authors.affiliation: Academic Urology Group, University of Cambridge, Cambridge, UK.
authors.forename: Phillipa
authors.initials: P
authors.lastname: Herbert
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Davis
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mizielinsk
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: J Athene
authors.initials: JA
authors.lastname: Lane
authors.affiliation: Department of Cellular Pathology, North Bristol NHS Trust, Bristol, UK.
authors.forename: Jon
authors.initials: J
authors.lastname: Oxley
authors.affiliation: Department of Cellular Pathology, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK.
authors.forename: Mary
authors.initials: M
authors.lastname: Robinson
authors.affiliation: Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Mason
authors.affiliation: Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: John
authors.initials: J
authors.lastname: Staffurth
authors.affiliation: Department of Urology and Surgery, Western General Hospital, University of Edinburgh, Edinburgh, UK.
authors.forename: Prasad
authors.initials: P
authors.lastname: Bollina
authors.affiliation: Academic Urology Unit, University of Sheffield, Sheffield, UK.
authors.forename: James
authors.initials: J
authors.lastname: Catto
authors.affiliation: Department of Urology, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Doble
authors.affiliation: Department of Urology, Queen Elizabeth Hospital, Birmingham, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Doherty
authors.affiliation: Department of Urology, Southmead Hospital and Bristol Urological Institute, Bristol, UK.
authors.forename: David
authors.initials: D
authors.lastname: Gillatt
authors.affiliation: Department of Urology, University Hospitals of Leicester, Leicester, UK.
authors.forename: Roger
authors.initials: R
authors.lastname: Kockelbergh
authors.affiliation: Department of Urology, Cardiff and Vale University Health Board, Cardiff, UK.
authors.forename: Howard
authors.initials: H
authors.lastname: Kynaston
authors.affiliation: Department of Urology, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Prescott
authors.affiliation: Department of Urology, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Paul
authors.affiliation: Department of Urology, Freeman Hospital, Newcastle-upon-Tyne, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Powell
authors.affiliation: Academic Urology Unit, University of Sheffield, Sheffield, UK.
authors.forename: Derek
authors.initials: D
authors.lastname: Rosario
authors.affiliation: Department of Urology, Southmead Hospital and Bristol Urological Institute, Bristol, UK.
authors.forename: Edward
authors.initials: E
authors.lastname: Rowe
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Donovan
authors.affiliation: Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
authors.forename: Freddie C
authors.initials: FC
authors.lastname: Hamdy
authors.affiliation: Academic Urology Group, University of Cambridge, Cambridge, UK; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK. Electronic address: den22@cam.ac.uk.
authors.forename: David E
authors.initials: DE
authors.lastname: Neal
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D002423:Cause of Death; D015331:Cohort Studies; D055088:Early Detection of Cancer; D004608:Eligibility Determination; D006801:Humans; D007610:Kallikreins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009362:Neoplasm Metastasis; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D011878:Radiotherapy / Q000379:methods; D016032:Randomized Controlled Trials as Topic; D006113:United Kingdom
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018931:Antineoplastic Agents, Hormonal; C557414:cixutumumab; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Prostate cancer; Prostate-specific antigen screening; Survival