IMPORTANCE Lung cancer in individuals who have never smoked (INS) is a growing global concern, with a rapidly increasing incidence and proportion among all lung cancer cases. Particularly in East Asia, opportunistic lung cancer screening (LCS) programs targeting INS have gained popularity. However, the sex-specific outcomes and drawbacks of screening INS remain unexplored, with data predominantly focused on women.

OBJECTIVE To compare LCS outcomes between Asian women and men with no smoking history.

DESIGN, SETTING, AND PARTICIPANTS This multicenter cohort study was conducted at health checkup centers in South Korea from 2009 to 2021. Participants included individuals aged 50 to 80 years with no smoking history who underwent low-dose computed tomography (LDCT) screening. Data were retrospectively analyzed from November 2023 to June 2024.

EXPOSURES Opportunistic LDCT screening for lung cancer.

MAIN OUTCOMES AND MEASURES Participants were followed up until December 2022 for the outcome of death. Lung cancer diagnosis, diagnostic characteristics, clinical course, and lung cancer-specific deaths (LCSD) were compared between women and men.

RESULTS A total of 21 062 participants (16 133 [76.6%] women and 4929 [23.4%] men) with a mean (SD) age of 59.8 (7.2) years were included. From baseline screening, 176 participants (139 women [0.9%] and 37 men [0.8%]) were diagnosed with lung cancer (screen-detected); 131 of 139 women (94.3%) and 33 of 37 men (89.2%) were diagnosed with stage 0 to I disease, with 133 of 139 women (95.7%) and 36 of 37 men (97.3%) having adenocarcinoma. There were no significant sex-based differences in stage or histologic type distribution. Among the 21 062 screened individuals, LCSD was reported in 8 women and 3 men during a mean (SD) follow-up of 83.8 (41.7) months. Multivariable analyses found no significant association between sex and cumulative hazards of lung cancer diagnosis (adjusted hazard ratio [aHR], 0.90 [95% CI, 0.64-1.26] for men vs women) or LCSD (aHR, 1.06 [95% CI, 0.28-4.00] for men vs women). The estimated 5-year lung cancer-specific survival rate was 97.7% for women and 100% for men with screen-detected lung cancer, showing no significant sex differences.

CONCLUSIONS AND RELEVANCE In this cohort study of Asian individuals with no smoking history who underwent LDCT screening, no significant sex-based differences were detected in lung cancer diagnosis, stage distribution, or LCSD. These findings suggest that men and women who have never smoked would experience similar risks of overdiagnosis with little to no benefit when exposed to indiscriminate screening.