Sex-based survival disparities in patients with stage I–III non-small cell lung cancer vary by treatment modality

Abstract

Introduction Female sex is a well-established prognostic factor in non-small cell lung cancer (NSCLC). Most prior studies are restricted to single-treatment cohorts and seldom include best supportive care (BSC), limiting the evaluation of sex-based median overall survival across the full treatment spectrum, BSC included. Methods We conducted a retrospective study of patients diagnosed with clinical stage I–III NSCLC treated with curative intent (surgery, radiotherapy, or chemoradiation) or primary BSC. Survival rate was analyzed using log-rank tests and multivariable Cox regression to adjust for confounding prognostic factors. Results In the total curative treatment cohort (n=1634), median overall survival (mOS) was 74.5 and 44.6 months in female and male patients, respectively [hazard ratio (HR) 0.60, P<0.001]. However, in the BSC cohort (n=234), mOS was similar between female (5.9 months) and male (5.8 months) patients (HR 0.93, P = 0.60). After stratification, mOS was not reached (females) versus 66.4 months (males) after surgery, (HR 0.58, P<0.001); 46.2 months (females) versus 33.0 months (males) after radiotherapy (HR 0.64, P<0.001); and 39.3 months (females) versus 26.9 months (males) after chemoradiation (HR 0.63, P<0.001). After multivariable adjustment, female survival benefit remained significant after curative-intent treatment overall (HR 0.72, P<0.001), surgery (HR 0.69, P = 0.003), and chemoradiation (HR 0.72, P = 0.02), but not after radiotherapy (HR 0.80, P = 0.12). Conclusions Female survival advantage in stage I–III NSCLC is treatment-dependent and absent in the BSC cohort. Prospective studies with more detailed clinical, biological, and sociodemographic data are needed to determine whether sex independently affects survival or reflects other prognostic factors.