Trends in lung cancer risk and screening eligibility affect overdiagnosis estimates

Abstract Objectives The degree of overdiagnosis due to lung cancer screening in the general US population remains unknown. Estimates may be influenced by the method used and by decreasing smoking trends, which reduce lung cancer risk and screening eligibility over time. Therefore, we aimed to estimate the degree of overdiagnosis due to lung cancer screening in the general US population, using three distinct methods. Material and Methods The MISCAN-Lung model was used to project lung cancer incidence and overdiagnosis in the general US population between 2018-2040, assuming perfect adherence to the United States Preventive Task Force recommendations. MISCAN-Lung was calibrated to the NLST and PLCO trials and incorporates birth-cohort-specific smoking trends and life expectancies. We estimated overdiagnosis using the cumulative excess-incidence approach, the annual excess-incidence approach, and the microsimulation approach. Results Using the cumulative excess-incidence approach, 10.5% of screen-detected cases were overdiagnosed in the 1950 birth-cohort compared to 5.9% in the 1990 birth-cohort. Incidence peaks and drops due to screening were larger for older birth-cohorts than younger birth-cohorts. In the general US population, these differing incidence peaks and drops across birth-cohorts overlap. Therefore, annual excess-incidence would be absent between 2029-2040, suggesting no overdiagnosis occurs. Using the microsimulation approach, overdiagnosis among screen-detected cases increased from 7.1%-9.5% between 2018-2040, while overdiagnosis among all lung cancer cases decreased from 3.7%-1.4%. Conclusion Overdiagnosis studies should use appropriate methods to account for trends in background risk and screening eligibility in the general population. Estimates from randomized trials, based on the cumulative excess-incidence approach, are not generalizable to the general population. The annual excess-incidence approach does not account for trends in background risk and screening eligibility, and falsely suggests no overdiagnosis occurs in the general population. Using the microsimulation approach, overdiagnosis was limited but not nil. Overdiagnosis increased among screen-detected cases, while overdiagnosis among all cases decreased.