Malignant pleural mesothelioma (MPM) is a rare disease with a very poor prognosis. Previous studies have indicated that women experience longer survival compared with men. We analyzed 16 267 eligible patients (21.3% females) in the National Cancer Database to evaluate which clinical factors are independently predictive of longer survival. After adjusting for all covariates, survival was significantly better in females compared with males [HRadj: 0.81, 95% confidence interval (CI): 0.77-0.85]. Other factors significantly associated with better survival were younger age at diagnosis, higher income, lower comorbidity score, epithelial histology, earlier stage and receipt of surgical or medical treatment. After propensity matching, survival was significantly better for females compared with males [hazard ratio (HR): 0.86, 95% CI: 0.80-0.94]. After propensity matching within the epithelial group, survival remained significantly better for females compared with males (HR: 0.85, 95% CI: 0.74-0.97). This study adds information to the known significant gender survival difference in MPM by disentangling the effect of gender from the effect of age and histology, two known independent factors affecting survival. Circulating estrogen, present in young but not older women, and higher expression of the estrogen receptor beta in epithelial mesothelioma have been suggested to play a role in gender survival differences. These findings may lead to exploring new therapeutic options, such as targeting estrogen receptor beta, and considering hormonal therapy including estrogens for patients with otherwise limited prognosis.
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