Optimal LDCT screening for never-smoking Asian women using integrated polygenic and environmental risk: a microsimulation modelling study
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Objective
To identify optimal initiation ages and screening intervals for low- dose computed tomography (LDCT) screening among never-smoking Asian women using an integrated polygenic risk score (PRS)–environmental tobacco smoke (ETS) risk model, and to evaluate the cost-effectiveness of alternative screening strategies at these optimized ages.
Design
Integrated PRS–ETS microsimulation modelling.
Setting
Japan.
Participants
Never-smoking women stratified into eight risk groups defined by combinations of PRS levels and ETS exposure.
Interventions
LDCT screening at intervals of 1 to 10 years, annual chest radiography (CXR), or no screening.
Main outcome measures
Costs, quality-adjusted life years (QALYs), incremental cost-effectiveness ratios (ICERs), net monetary benefits, lung adenocarcinoma incidence and mortality, and optimal LDCT initiation ages. Sensitivity analyses used a willingness-to-pay threshold of US$50,000 per QALY gained.
Results
Optimal initiation ages ranged from 40 to 55 years across the eight PRS–ETS risk groups, with higher PRS–ETS risk associated with younger optimal initiation ages. Annual LDCT was the most cost-effective strategy across all PRS–ETS risk strata, yielding an ICER of US$40,471 per QALY in the lowest risk stratum and becoming cost-saving in higher risk strata. Over a lifetime, annual LDCT averted 8,534 lung adenocarcinoma deaths compared with annual CXR and 14,940 deaths compared with no screening.
Conclusions
Tailoring LDCT initiation age across integrated PRS–ETS risk groups maximizes mortality reduction achievable with cost-effective annual LDCT screening among never-smoking Asian women. These findings highlight an urgent limitation of global lung cancer screening guidelines that rely exclusively on smoking history and provide policy-ready evidence supporting the integration of PRS and ETS into future recommendations for precision LDCT screening for never-smoking populations.
