title: Selecting High-Risk Individuals for Lung Cancer Screening: A Prospective Evaluation of Existing Risk Models and Eligibility Criteria in the German EPIC Cohort.
abstract: Lung cancer risk prediction models are considered more accurate than the eligibility criteria based on age and smoking in identification of high-risk individuals for screening. We externally validated four lung cancer risk prediction models (Bach, Spitz, LLP, and PLCO(M2012)) among 20,700 ever smokers in the EPIC-Germany cohort. High-risk subjects were identified using the eligibility criteria applied in clinical trials (NELSON/LUSI, DLCST, ITALUNG, DANTE, and NLST) and the four risk prediction models. Sensitivity, specificity, and positive predictive value (PPV) were calculated based on the lung cancers diagnosed in the first 5 years of follow-up. Decision curve analysis was performed to compare net benefits. The number of high-risk subjects identified by the eligibility criteria ranged from 3,409 (NELSON/LUSI) to 1,458 (NLST). Among the eligibility criteria, the DLCST produced the highest sensitivity (64.13%), whereas the NLST produced the highest specificity (93.13%) and PPV (2.88%). The PLCO(M2012) model showed the best performance in external validation (C-index: 0.81; 95% CI, 0.76-0.86; E/O: 1.03; 95% CI, 0.87-1.23) and the highest sensitivity, specificity, and PPV, but the superiority over the Bach model and the LLP model was modest. All the models but the Spitz model showed greater net benefit over the full range of risk estimates than the eligibility criteria. We concluded that all of the lung cancer risk prediction models apart from the Spitz model have a similar accuracy to identify high-risk individuals for screening, but in general outperform the eligibility criteria used in the screening trials.
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. k.li@dkfz.de r.kaaks@dkfz.de.
authors.forename: Kuanrong
authors.initials: K
authors.lastname: Li
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Hüsing
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Disorn
authors.initials: D
authors.lastname: Sookthai
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Bergmann
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Becker
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. k.li@dkfz.de r.kaaks@dkfz.de.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D002986:Clinical Trials as Topic; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D005858:Germany; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000453:epidemiology; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D008962:Models, Theoretical; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012907:Smoking; D016896:Treatment Outcome