• Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, Texas (I.T., M.H.).
• Department of Epidemiology, University of Michigan, Ann Arbor, Michigan (P.C., J.J.).
• Erasmus MC-University Medical Center, Rotterdam, the Netherlands (K. de N., K. ten H., H.J. de K.).
• Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York (M.B.).
• Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts (V.M., G.S.G.).
• Department of Health Sciences, Brock University, St. Catharines, Ontario, Canada (M.T.).
• Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland (E.J.F.).
• Division of General Internal Medicine, Department of Medicine, Mount Sinai Hospital, New York, New York (C.Y.K.).
• Department of Epidemiology, University of Michigan, Ann Arbor, Michigan, and Department of Integrative Oncology, BC Cancer Research Institute, British Columbia, Canada (R.M.).
• Department of Biomedical Data Sciences, Stanford University, Stanford, California (S.K.P.).

BACKGROUND: In their 2021 lung cancer screening recommendation update, the U.S. Preventive Services Task Force (USPSTF) evaluated strategies that select people based on their personal lung cancer risk (risk model-based strategies), highlighting the need for further research on the benefits and harms of risk model-based screening.

OBJECTIVE: To evaluate and compare the cost-effectiveness of risk model-based lung cancer screening strategies versus the USPSTF recommendation and to explore optimal risk thresholds.

DESIGN: Comparative modeling analysis.

DATA SOURCES: National Lung Screening Trial; Surveillance, Epidemiology, and End Results program; U.S. Smoking History Generator.

TARGET POPULATION: 1960 U.S. birth cohort.

TIME HORIZON: 45 years.

PERSPECTIVE: U.S. health care sector.

INTERVENTION: Annual low-dose computed tomography in risk model-based strategies that start screening at age 50 or 55 years, stop screening at age 80 years, with 6-year risk thresholds between 0.5% and 2.2% using the PLCOm2012 model.

OUTCOME MEASURES: Incremental cost-effectiveness ratio (ICER) and cost-effectiveness efficiency frontier connecting strategies with the highest health benefit at a given cost.

RESULTS OF BASE-CASE ANALYSIS: Risk model-based screening strategies were more cost-effective than the USPSTF recommendation and exclusively comprised the cost-effectiveness efficiency frontier. Among the strategies on the efficiency frontier, those with a 6-year risk threshold of 1.2% or greater were cost-effective with an ICER less than $100 000 per quality-adjusted life-year (QALY). Specifically, the strategy with a 1.2% risk threshold had an ICER of $94 659 (model range, $72 639 to $156 774), yielding more QALYs for less cost than the USPSTF recommendation, while having a similar level of screening coverage (person ever-screened 21.7% vs. USPSTF's 22.6%).

RESULTS OF SENSITIVITY ANALYSES: Risk model-based strategies were robustly more cost-effective than the 2021 USPSTF recommendation under varying modeling assumptions.

LIMITATION: Risk models were restricted to age, sex, and smoking-related risk predictors.

CONCLUSION: Risk model-based screening is more cost-effective than the USPSTF recommendation, thus warranting further consideration.

PRIMARY FUNDING SOURCE: National Cancer Institute (NCI).