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.

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.