Comparison of discrimination performance of 11 lung cancer risk models for predicting lung cancer in a prospective cohort of screening-age adults from Germany followed over 17 years

Abstract

Randomized trials have demonstrated considerable reduction in lung cancer (LC) mortality by screening pre-selected heavy smokers with low-dose computed tomography (LDCT). Newer screening guidelines recommend refined LC risk models for selecting the target population for screening. We aimed to evaluate and compare the discrimination performance of LC risk models and previously used trial criteria in predicting LC incidence and mortality in a large German cohort of screening-age adults. Within ESTHER, a population-based prospective cohort study conducted in Saarland, Germany, 4812 ever smokers aged 50-75 years were followed up with respect to LC incidence and mortality for up to 17 years. We quantified the performance of 11 different LC risk models by the area under the curve (AUC) and compared the proportion of correctly predicted LC cases between the best performing models and the LDCT trial criteria. Risk prediction of LC incidence in the ESTHER ever smokers was best for the Bach model, LCRAT and LCDRAT with AUCs ranging from 0.782 to 0.787, from 0.770 to 0.774, and from 0.765 to 0.771 for the follow-up time periods of cases identified at 6, 11, and 17 years, respectively. At cutoffs yielding comparable positivity rates as the LDCT trial criteria, these models would have identified between 11.8 (95% CI 3.0-20.5) and 17.6 (95% CI 10.1-25.2) percent units higher proportions of LC cases occurring during the initial 6 years of follow-up. Use of LC risk models is expected to result in substantially greater potential to identify people at highest risk of LC, suggesting enhanced potential for reducing LC mortality by LC screening.

Keywords: Cancer prevention and screening; LDCT; Lung cancer; Risk prediction; Smoking exposure.