After differences in implementation and settings were accounted for, two important prostate cancer screening trials provide compatible evidence that screening reduces prostate cancer mortality. These findings suggest that current US guidelines recommending against routine PSA-based screening may be revised. However, questions remain about how to implement screening so that the benefits outweigh the potential harms of over-diagnosis and over-treatment.
Current guidelines from the United States Preventive Services Task Force (USPSTF) recommend against prostate-specific antigen (PSA) screening for prostate cancer because the evidence for the test showed very low probability that it would reduce the risk of dying from prostate cancer. This recommendation relied heavily on results from the ERSPC (European Randomised Study of Screening for Prostate Cancer) and the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial), which offered conflicting results. The ERSPC showed a significant reduction and the PLCO showed no reduction. However, differences in study implementation, compliance, and practice settings may account for this conflict.
A team of investigators from the University of Michigan and the National Cancer Institute sought to formally test whether the effects of screening on prostate cancer mortality differed between the ERSPC and PLCO and to estimate the effects of screening in both trials relative to no screening. Using a mathematical model to account for differences in implementation compliance, and practice settings, they found no evidence that the effects of screening compared to no screening differed between ERSPC and PLCO and inferred that screening could significantly reduce prostate cancer deaths.
The author of an accompanying editorial from Sloan Kettering Cancer Centre hopes that this paper will put to rest the question of whether PSA screening reduces prostate cancer mortality. Instead, the discussion should focus on how to implement screening so that the benefit outweighs the harms of over-diagnosis and over-treatment.
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.
Authors
Alex Tsodikov; Roman Gulati; Eveline AM Heijnsdijk; Paul F Pinsky; Sue M Moss; Sheng Qiu; Tiago M de Carvalho; Jonas Hugosson; Christine D Berg; Anssi Auvinen; Gerald L Andriole; Monique J Roobol; E David Crawford; Vera Nelen; Maciej Kwiatkowski; Marco Zappa; Marcos Luján; Arnauld Villers; Eric J Feuer; Harry J de Koning; Angela B Mariotto; Ruth Etzioni
[link url="https://www.sciencedaily.com/releases/2017/09/170904181723.htm"]American College of Physicians material[/link]
[link url="http://annals.org/aim/article/2652567/reconciling-effects-screening-prostate-cancer-mortality-erspc-plco-trials"]Annals of Internal Medicine abstract[/link]
Annals of Internal Medicine editorialhttp://annals.org/aim/article/2652568/prostate-cancer-screening-time-question-how-optimize-ratio-benefits-harms