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

Eur Urol. 2014 Feb;65(2):329-36. doi: 10.1016/j.eururo.2013.08.005. Epub 2013 Aug 11.


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.

Design, setting, and participants: 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.

Outcome measurements and statistical analysis: 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.

Results and limitations: 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.

Trial registration: ISRCTN49127736.

Keywords: Biopsy; Contamination; Nonattendance; PALGA; Prostate-specific antigen; Prostatic neoplasms; Screening.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biopsy
  • Humans
  • Kallikreins / blood*
  • Male
  • Mass Screening / methods*
  • Middle Aged
  • Netherlands / epidemiology
  • Odds Ratio
  • Patient Compliance*
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Prostate-Specific Antigen / blood*
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / mortality*
  • Prostatic Neoplasms / pathology
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Up-Regulation


  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen

Associated data

  • ISRCTN/ISRCTN49127736