Prostate cancer mortality reduction by prostate-specific antigen-based screening adjusted for nonattendance and contamination in the European Randomised Study of Screening for Prostate Cancer (ERSPC).
Roobol MJ., Kerkhof M., Schröder FH., Cuzick J., Sasieni P., Hakama M., Stenman UH., Ciatto S., Nelen V., Kwiatkowski M., Lujan M., Lilja H., Zappa M., Denis L., Recker F., Berenguer A., Ruutu M., Kujala P., Bangma CH., Aus G., Tammela TLJ., Villers A., Rebillard X., Moss SM., de Koning HJ., Hugosson J., Auvinen A.
BACKGROUND: Prostate-specific antigen (PSA) based screening for prostate cancer (PCa) has been shown to reduce prostate specific mortality by 20% in an intention to screen (ITS) analysis in a randomised trial (European Randomised Study of Screening for Prostate Cancer [ERSPC]). This effect may be diluted by nonattendance in men randomised to the screening arm and contamination in men randomised to the control arm. OBJECTIVE: To assess the magnitude of the PCa-specific mortality reduction after adjustment for nonattendance and contamination. DESIGN, SETTING, AND PARTICIPANTS: We analysed the occurrence of PCa deaths during an average follow-up of 9 yr in 162,243 men 55-69 yr of age randomised in seven participating centres of the ERSPC. Centres were also grouped according to the type of randomisation (ie, before or after informed written consent). INTERVENTION: Nonattendance was defined as nonattending the initial screening round in ERSPC. The estimate of contamination was based on PSA use in controls in ERSPC Rotterdam. MEASUREMENTS: Relative risks (RRs) with 95% confidence intervals (CIs) were compared between an ITS analysis and analyses adjusting for nonattendance and contamination using a statistical method developed for this purpose. RESULTS AND LIMITATIONS: In the ITS analysis, the RR of PCa death in men allocated to the intervention arm relative to the control arm was 0.80 (95% CI, 0.68-0.96). Adjustment for nonattendance resulted in a RR of 0.73 (95% CI, 0.58-0.93), and additional adjustment for contamination using two different estimates led to estimated reductions of 0.69 (95% CI, 0.51-0.92) to 0.71 (95% CI, 0.55-0.93), respectively. Contamination data were obtained through extrapolation of single-centre data. No heterogeneity was found between the groups of centres. CONCLUSIONS: PSA screening reduces the risk of dying of PCa by up to 31% in men actually screened. This benefit should be weighed against a degree of overdiagnosis and overtreatment inherent in PCa screening.