OBJECTIVES: This study evaluates the integration of proteomics tests with standard LDCT for lung cancer screening in high-risk smokers, addressing LDCT's limitations of low compliance, high costs, and frequent empty scans.

METHODS: The target population was high-risk smokers aged 55-70 years simulated separately for the UK and US. Each age group was followed until age 90, and screened to 70. Annual cancer incidence and mortality rates (due to lung cancer and other causes) were obtained and predicted using data from the Global Burden of Disease (GBD) study. Life years were calculated and converted to QALYs using GBD disability weights and EQ-5D for cancer patients and healthy individuals, respectively. The number of primary tests and biopsies was determined based on a biennial screening program. Proteomics tests were conducted prior to LDCT scans, with positive results leading to LDCT and then to biopsies. Costs of screening, treatment of local and advanced cancers, and end-of-life care were recorded. Outputs included costs, QALYs, deaths, and utilizations. ICER was used for comparisons. All simulations were run 1000 times.

RESULTS: All three proteomics tests significantly improved cost savings and QALYs compared to both no screening and LDCT alone, with ICERs ranging from -$10,000 to -$30,000. Incorporating proteomics before LDCT in the US resulted in cost savings of $3.4 billion ($2.7 to $4 billion) and $1.7 billion ($1.2 to $2.3 billion) compared to LDCT and no screening, respectively. Additionally, 6,870 deaths and 876,000 unnecessary biopsies were prevented compared to no screening and LDCT alone. Similar benefits were observed in the UK cohort, consistently showing negative ICERs.

CONCLUSIONS: Integrating low-cost proteomics tests into lung cancer screening for high-risk smokers reduces costs and enhances QALYs compared to current methods and no screening. Proteomics-based strategies provide a more efficient screening approach in high-risk populations globally.