Association Between Obesity and Sex-Related Survival Difference in Lung Cancer

Survival discrepancy between male and female patients in lung cancer is a well-known, but still poorly understood phenomenon. Previous studies have used different patient cohorts and clinical covariates and have not included obesity, which is associated with longer lung cancer survival. We evaluated the relationship between survival, obesity, sex and other covariates using comprehensive, harmonized patient cohorts and a federated analysis approach.

Initial analyses were done in a retrospective, real-world cohort of 7,327 patients with lung cancer diagnosed at the Helsinki University Hospital from 2015 to 2024. Patients were stratified by BMI, and univariate and multivariate analyses of survival were performed. External validation of univariate analyses was performed on data from four European university hospitals (n = 12,700).

Higher BMI was associated with a smaller sex-related survival difference. In the normal BMI cohort (18.5-25 kg/m²), the 2-year overall survival was 46% in females and 29% in males (P < .01). In the high BMI cohort, the difference was 51% versus 41% (P < .01). Similar trends were observed in the validation sites, with some variation. The largest effect of high BMI was observed in squamous cell carcinoma. When full multivariate analysis was performed separately for high and normal BMI patients, the effect of male sex on survival was 32% smaller among high BMI patients.

Higher BMI was associated with reduced survival gap between sexes, emphasizing the value of comprehensive covariate reporting in future clinical trials and observational studies.