Reconciling the Effects of Screening on Prostate Cancer Mortality in the ERSPC and PLCO Trials

Abstract

Background: The ERSPC (European Randomized Study of Screening for Prostate Cancer) found that screening reduced prostate cancer mortality, but the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) found no reduction.

Objective: To evaluate whether effects of screening on prostate cancer mortality relative to no screening differed between the ERSPC and PLCO.

Design: Cox regression of prostate cancer death in each trial group, adjusted for age and trial. Extended analyses accounted for increased incidence due to screening and diagnostic work-up in each group via mean lead times (MLTs), which were estimated empirically and using analytic or microsimulation models.

Setting: Randomized controlled trials in Europe and the United States.

Participants: Men aged 55 to 69 (ERSPC) or 55 to 74 (PLCO) years at randomization.

Intervention: Prostate cancer screening.

Measurements: Prostate cancer incidence and survival from randomization; prostate cancer incidence in the United States before screening began.

Results: Estimated MLTs were similar in the ERSPC and PLCO intervention groups but were longer in the PLCO control group than the ERSPC control group. Extended analyses found no evidence that effects of screening differed between trials (P = 0.37 to 0.47 [range across MLT estimation approaches]) but strong evidence that benefit increased with MLT (P = 0.0027 to 0.0032). Screening was estimated to confer a 7% to 9% reduction in the risk for prostate cancer death per year of MLT. This translated into estimates of 25% to 31% and 27% to 32% lower risk for prostate cancer death with screening as performed in the ERSPC and PLCO intervention groups, respectively, compared with no screening.

Limitation: The MLT is a simple metric of screening and diagnostic work-up.

Conclusion: After differences in implementation and settings are accounted for, the ERSPC and PLCO provide compatible evidence that screening reduces prostate cancer mortality.

Primary funding source: National Cancer Institute.

Figures

Figure 1. Estimated mean lead times (years) in the intervention and control arms of the ERSPC and PLCO relative to a hypothetical no-screening setting (where lead time is always zero)

Estimated MLTs are visualized as increasing to the left to suggest the extent to which prostate cancer diagnosis is advanced by more intensive screening and diagnostic workup. ERSPC=European Randomized Study of Screening for Prostate Cancer; PLCO=Prostate, Lung, Colorectal, and Ovarian cancer screening trial; FHCRC=Fred Hutchinson Cancer Research Center; MISCAN=Erasmus University Medical Center MIcrosimulation SCreening ANalysis; UMICH=University of Michigan

Figure 2. Prostate cancer survival from randomization in the ERSPC and PLCO estimated by Kaplan-Meier or Cox regression model using mean lead time estimated using the empirical approach

ERSPC=European Randomized Study of Screening for Prostate Cancer; PLCO=Prostate, Lung, Colorectal, and Ovarian cancer screening trial