Sex is a strong prognostic factor in stage IV non-small-cell lung cancer patients and should be considered in survival rate estimation

Cancer Epidemiol. 2020 Aug;67:101737. doi: 10.1016/j.canep.2020.101737. Epub 2020 May 22.


Background: Biological differences between the sexes have a major impact on disease and treatment outcome. In this paper, we evaluate the prognostic value of sex in stage IV non-small-cell lung cancer (NSCLC) in the context of routine clinical data, and compare this information with other external datasets.

Methods: Clinical data from stage IV NSCLC patients from Hospital Puerta de Hierro (HPH) were retrieved from electronic health records using big data analytics (N = 397). In addition, data from the Spanish Lung Cancer Group (GECP) Tumor Registry (N = 1382) and from a published study available from the cBioPortal (MSK) (N = 601) were analyzed. Survival curves were estimated using the Kaplan-Meier method. A Cox proportional hazards regression model was used to assess the prognostic value of sex. A meta-analysis to compare the outcome for males and females in terms of overall survival (OS) and progression free survival (PFS) was performed.

Results: The median OS time was 12 months for males and 19 months for females (overall HR = 0.77; 95% CI: 0.68-0.87; P < 0.001). Similarly, females with stage IV NSCLC harboring an EGFR-sensitizing mutation lived significantly longer than males (median OS: males, 19 months; females, 32 months) with a lower risk of death compared with males (overall HR = 0.75; 95% CI: 0.67-0.84). In addition, female patients benefited more from EGFR inhibitors in terms of PFS and OS (overall HR = 0.45; 95% CI: 0.32-0.64, and HR = 0.62; 95% CI: 0.48-0.80, respectively). Median PFS was 21 months in females and 12 months in males (P < 0.001).

Conclusions: Using routine clinical data we confirmed the previous finding that among stage IV NSCLC patients, females had a significantly better prognosis than males. The effect size of the sex was notable, highlighting the fact that survival rates are usually estimated and patients are generally managed without considering the sexes separately, which may lead to suboptimal results.

Keywords: EGFR; Female; Gender; Non-small cell lung cancer; Sex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Male
  • Meta-Analysis as Topic
  • Middle Aged
  • Mutation*
  • Neoplasm Staging
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use
  • Sex Factors
  • Survival Rate


  • Protein Kinase Inhibitors
  • EGFR protein, human
  • ErbB Receptors