Combined Biomarker and Computed Tomography Screening Strategies for Lung Cancer: Projections of Health and Economic Tradeoffs in the US Population

Background: Lung cancer screening with computed tomography (CT) of individuals who meet certain age and smoking history criteria is the current standard-of-care.

Methods: Using a published simulation model, we compared outcomes associated with seven biomarker+CT screening strategies to CT screening alone using CMS eligibility criteria. We assumed that the biomarker: had conditionally independent performance; was used for first-line screening in some, or all, individuals screened; and could be extended to CMS-ineligible smokers. Strategies differed by inclusion criteria (e.g. pack-years) and proportion of individuals for whom CT remained the first-line test. Each model run simulated a combined cohort of one million men and one million women born in 1950. Primary outcomes were cancer-specific mortality reduction and screening costs; biomarker costs were measured relative to CT. Efficiency frontiers identified optimal health and economic trade-offs. Sensitivity analysis evaluated the stability of results.

Results: Standard-of-care screening yielded an 8.3% cancer-specific mortality reduction in the simulated U.S. population (screened+unscreened individuals). For a biomarker test with 75% sensitivity and 95% specificity, mortality reductions across biomarker+CT strategies ranged from 7.0% to 23.9%. If the biomarker's cost was >0.86× that of CT, standard-of-care screening remained on the efficiency frontier, indicating that health and economic trade-offs were equally (or more) efficient relative to all biomarker+CT strategies. Biomarker+CT strategy costs were principally driven by biomarker specificity; mortality reduction was driven by sensitivity.

Conclusion: Combined biomarker+CT strategies have the potential to improve future lung cancer screening effectiveness in the U.S. and achieve economic efficiency that is greater than the current standard-of-care.