A. Kowada
ObjectiveTo 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.
DesignIntegrated PRS-ETS microsimulation modelling.
SettingJapan.
ParticipantsNever-smoking women stratified into eight risk groups defined by combinations of PRS levels and ETS exposure.
InterventionsLDCT screening at intervals of 1 to 10 years, annual chest radiography (CXR), or no screening.
Main outcome measuresCosts, 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.
ResultsOptimal 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.
ConclusionsTailoring 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.