Sex Differences in Overall Survival Among Patients with Non-Small-Cell Lung Cancer Across Clinical Stages: A Population-Based SEER Study

Background/Objective: Sex-based disparities in cancer outcomes have gained increasing attention in women’s health research. We examined the relationship between sex and overall survival (OS) among patients with non-small-cell lung cancer (NSCLC), with particular emphasis on the survival advantage observed in women across different clinical stages and treatment settings. Sex-related differences in cancer outcomes have become an important focus in oncology and women’s health research. This study aimed to investigate the association between sex and overall survival (OS) in patients with non-small-cell lung cancer (NSCLC), with particular attention to the observed survival advantage in women across clinical stages and treatment contexts. Methods: A total of 129,864 patients diagnosed with NSCLC were identified, including 78,460 men and 51,404 women. Demographic characteristics, socioeconomic status, tumor features, treatment modalities, and survival outcomes were compared between sexes. Kaplan–Meier survival analyses and stage-stratified Cox proportional hazards models were used to evaluate overall survival differences between female and male patients. Results: Women demonstrated significantly superior OS compared with men across all stages of NSCLC (all p < 0.001). This survival advantage persisted regardless of receipt of chemotherapy. Among patients receiving chemotherapy, survival improvements were observed in both sexes; however, women consistently exhibited longer median OS at each stage. From stage IB to IV, median OS in women was 52.0, 30.0, 13.0, and 5.0 months, respectively, compared with 33.0, 23.0, 11.0, and 4.0 months in men. Notably, the magnitude of sex-related survival differences was more pronounced in earlier stages (IB/II) than in advanced stages (III/IV), suggesting potential biological or treatment response differences favoring women. Age-stratified analyses further demonstrated that women older than 45 years experienced a consistent survival advantage across all stages. Multivariable Cox regression confirmed that female sex was independently associated with reduced mortality risk at every stage (HRs ranging from 0.766 to 0.857; all p < 0.001). Conclusions: Women with NSCLC exhibit a significant and independent survival advantage over men across clinical stages, regardless of chemotherapy status, particularly among patients older than 45 years. These findings highlight the importance of considering sex in prognostic assessment and support further investigation into factors contributing to survival differences in NSCLC.