Effects of Causal and Noncausal Components of Screening on Prostate Cancer Mortality: A Mediation Analysis from the Dutch, Finnish, and Swedish Centers of the European Randomized Study of Screening for Prostate Cancer.

BACKGROUND AND

OBJECTIVE

The European Randomized Study of Screening for Prostate Cancer (ERSPC) has shown that prostate-specific antigen (PSA)-based screening reduces prostate cancer (PCa)-specific mortality (PCSM). However, the mediating role of a stage shift and curative treatment in the causal pathway from screening to reduced PCSM has not been elucidated.

METHODS

In the ERSPC trial, men were randomly allocated to either a screening arm, with regular PSA measurements, or a control arm. During 16-yr follow-up, 8046 men from Finland, 3701 from the Netherlands, and 1382 from Sweden were diagnosed with PCa and were aged 55-69 yr at the time of randomization. A directed acyclic graph was used to define the impact of screening on the PCa-specific restricted mean survival time (RMST) after randomization, mediated by risk group and treatment at diagnosis.

KEY FINDINGS AND LIMITATIONS: The absolute increase in RMST over 16 yr for men in the screening arm versus the control arm was 0.13 yr (95% confidence interval [CI] 0.05-0.22) in Finland, 0.48 yr (95% CI 0.24-0.62) in the Netherlands, and 0.44 yr (95% CI 0.22-0.68) in Sweden. This effect was mainly attributable to risk group at diagnosis, and not through treatment at the time of diagnosis. A limitation of the study is that we only included the three largest ERSPC centers.

CONCLUSIONS AND CLINICAL IMPLICATION: The reduced PCSM achieved by early PCa detection via PSA-based screening is caused by more favorable prognostic features and subsequent improved treatment outcomes. Our findings confirm that the observed results are a causal effect of screening.