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The efficacy of prostate‐specific antigen screening: Impact of key components in the ERSPC and PLCO trials
Author(s) -
de Koning Harry J.,
Gulati Roman,
Moss Sue M.,
Hugosson Jonas,
Pinsky Paul F.,
Berg Christine D.,
Auvinen Anssi,
Andriole Gerald L.,
Roobol Monique J.,
Crawford E. David,
Nelen Vera,
Kwiatkowski Maciej,
Zappa Marco,
Luján Marcos,
Villers Arnauld,
de Carvalho Tiago M.,
Feuer Eric J.,
Tsodikov Alex,
Mariotto Angela B.,
Heijnsdijk Eveline A. M.,
Etzioni Ruth
Publication year - 2018
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.31178
Subject(s) - medicine , prostate cancer , prostate specific antigen , oncology , confidence interval , randomized controlled trial , prostate , clinical trial , prostate biopsy , cancer , gynecology
BACKGROUND The European Randomized Study of Screening for Prostate Cancer (ERSPC) demonstrated that prostate‐specific antigen (PSA) screening significantly reduced prostate cancer mortality (rate ratio, 0.79; 95% confidence interval, 0.69‐0.91). The US Prostate, Lung, Colorectal, and Ovarian (PLCO) trial indicated no such reduction but had a wide 95% CI (rate ratio for prostate cancer mortality, 1.09; 95% CI, 0.87‐1.36). Standard meta‐analyses are unable to account for key differences between the trials that can impact the estimated effects of screening and the trials' point estimates. METHODS The authors calibrated 2 microsimulation models to individual‐level incidence and mortality data from 238,936 men participating in the ERSPC and PLCO trials. A cure parameter for the underlying efficacy of screening was estimated by the models separately for each trial. The authors changed step‐by‐step major known differences in trial settings, including enrollment and attendance patterns, screening intervals, PSA thresholds, biopsy receipt, control arm contamination, and primary treatment, to reflect a more ideal protocol situation and differences between the trials. RESULTS Using the cure parameter estimated for the ERSPC, the models projected 19% to 21% and 6% to 8%, respectively, prostate cancer mortality reductions in the ERSPC and PLCO settings. Using this cure parameter, the models projected a reduction of 37% to 43% under annual screening with 100% attendance and biopsy compliance and no contamination. The cure parameter estimated for the PLCO trial was 0. CONCLUSIONS The observed cancer mortality reduction in screening trials appears to be highly sensitive to trial protocol and practice settings. Accounting for these differences, the efficacy of PSA screening in the PLCO setting is not necessarily inconsistent with ERSPC results. Cancer 2018;124:1197‐206. © 2017 American Cancer Society .