| Summary: | 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 Centers for Medicare & Medicaid Services 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 Centers for Medicare & Medicaid Services–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 tradeoffs. Sensitivity analysis evaluated the stability of results. Results: Standard-of-care screening yielded an 8.3% cancer-specific mortality reduction in the simulated US 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 tradeoffs 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 United States and achieve economic efficiency that is greater than the current standard-of-care.
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