title: Prostate-specific antigen-based prostate cancer screening: reduction of prostate cancer mortality after correction for nonattendance and contamination in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer.
abstract: BACKGROUND
  Large randomized screening trials provide an estimation of the effect of screening at a population-based level. The effect of screening for individuals, however, is diluted by nonattendance and contamination in the trial arms.
  
  
  OBJECTIVE
  To determine the prostate cancer (PCa) mortality reduction from screening after adjustment for nonattendance and contamination.
  
  
  METHODS
  A total of 34,833 men in the core age group, 55-69 yr, were randomized to a screening or control arm in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC). Prostate-specific antigen (PSA) testing was offered to all men in the screening arm at 4-yr intervals. A prostate biopsy was offered to men with an elevated PSA. The primary end point was PCa-specific mortality.
  
  
  METHODS
  Nonattendance was defined as nonparticipation in the screening arm. Contamination in the control arm was defined as receiving asymptomatic PSA testing or a prostate biopsy in the absence of symptoms. Relative risks (RRs) were calculated with an intention to screen (ITS) analysis and after correction for nonattendance and contamination using a method that preserves the benefits obtained by randomization.
  
  
  CONCLUSIONS
  The ITS analysis resulted in an RR of 0.68 (95% confidence interval [CI], 0.53-0.89) in favor of screening at a median follow-up of 13 yr. Correction for both nonattendance and contamination resulted in an RR of 0.49 (95% CI, 0.27-0.87) in favor of screening.
  
  
  CONCLUSIONS
  PCa screening as conducted in the Rotterdam section of the ERSPC can reduce the risk of dying from PCa up to 51% for an individual man choosing to be screened repeatedly compared with a man who was not screened. This benefit of screening should be balanced against the harms of overdiagnosis and subsequent overtreatment.
  
  
  BACKGROUND
  ISRCTN49127736.
authors: Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: l.bokhorst@erasmusmc.nl.
authors: Leonard P
authors: LP
authors: Bokhorst
authors: Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Chris H
authors: CH
authors: Bangma
authors: Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Geert J L H
authors: GJ
authors: van Leenders
authors: STAR-Medical Diagnostic Center, Rotterdam, The Netherlands.
authors: Jan J
authors: JJ
authors: Lous
authors: Centre for Cancer Prevention, Wolfson Institute for Preventive Medicine, Queen Mary University of London, London, United Kingdom.
authors: Sue M
authors: SM
authors: Moss
authors: Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Fritz H
authors: FH
authors: Schröder
authors: Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Monique J
authors: MJ
authors: Roobol
mesh_terms: D000368:Aged; D001706:Biopsy; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D010349:Patient Compliance; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000401:mortality* / Q000473:pathology; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D015854:Up-Regulation
chemical_list: C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Biopsy; Contamination; Nonattendance; PALGA; Prostate-specific antigen; Prostatic neoplasms; Screening