Hormonal Status May Contribute to Sex-Based Survival Differences in Epithelioid Peritoneal Mesothelioma

Background Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is central to treating patients with epithelioid peritoneal mesothelioma (EPM). Male sex is a negative prognostic factor in mesothelioma, but the reasons for this remain unclear. We evaluated the impact of sex and age, as a proxy for menopause status, on treatment patterns and survival for EPM. Patients and Methods Adults with unicavitary EPM were identified in the National Cancer Database (NCDB) (2006–2020). Predictors of CRS/HIPEC receipt were evaluated using logistic regression. Among patients who underwent CRS/HIPEC, variables impacting overall survival (OS) were evaluated using Cox regression. Patients were stratified by age (≤ 40 years and ≥ 60 years) into younger male, older male, premenopausal female, and postmenopausal female patients for subgroup analysis. Results Of 1868 patients meeting inclusion criteria, 28.1% ( n = 526) received CRS/HIPEC; of those, 286 (54.4%) were male. Male sex (odds ratio, OR 1.054, p = 0.015), younger age (OR 0.996, p < 0.001), and treatment at an academic center (OR 1.253, p < 0.001) were independently associated with receiving CRS/HIPEC. Males had worse OS than females after CRS/HIPEC on multivariable regression (hazard ratio, HR 1.647, p = 0.003). Upon age-stratification of patients who underwent CRS/HIPEC, premenopausal females had significantly improved OS compared with younger male, older male, and postmenopausal female patients on Kaplan–Meier analysis (all p < 0.05). Female sex significantly predicted survival in younger (HR 0.267, p = 0.012) but not older patients (HR 0.676, p = 0.061). Conclusions Premenopausal women with EPM undergoing CRS/HIPEC had significantly improved OS compared with both males and postmenopausal females, suggesting a hormonal influence on outcomes. Future studies to elucidate the biological mechanisms underlying this sex-based disparity are necessary.