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

Our plain-English summary of Hormonal Status May Contribute to Sex-Based Survival Differences in Epithelioid Peritoneal Mesothelioma, by K.C. Cummins, O. Sears, E.R. Bitar, et al (Annals of Surgical Oncology, 2026).

The study

• Authors: K.C. Cummins, O. Sears, E.R. Bitar, C. Shen, A. Tsung, S.M. Ruff
• Journal: Annals of Surgical Oncology
• Published: 2026;33(6):5304-5314
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

© 2026. The Author(s).

In plain English

This study used US National Cancer Database records of adults diagnosed 2006 to 2020 with epithelioid peritoneal mesothelioma, a cancer of the abdominal lining. Patients with disease in both abdomen and chest were excluded. Asbestos exposure was not examined. Of 1868 patients, 526 (28.2%) received cytoreductive surgery with heated abdominal chemotherapy (CRS/HIPEC). Among those 526, women had better overall survival than men after adjusting for other factors (hazard ratio 0.635, 95% confidence interval 0.452 to 0.890, p = 0.008). The authors used age as a stand-in for menopause: 40 or younger counted as premenopausal, 60 or older as postmenopausal. The subgroup was 41 premenopausal women, 76 postmenopausal women, 31 younger men and 154 older men. Median survival was not reached for premenopausal women at 175 months, versus 66.6 months for postmenopausal women, 116.9 for younger men and 39.1 for older men. Female sex predicted better survival among younger patients but was not statistically significant among older patients. The authors concluded that sex hormones may play a role. They noted that age only approximates menopause and that cause of death was unrecorded.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective analysis of a national cancer registry (National Cancer Database), using logistic regression for who received CRS/HIPEC and Kaplan-Meier and Cox regression for overall survival
• Who was studied: 1868 adults (18 and older) in the US National Cancer Database diagnosed with epithelioid peritoneal mesothelioma between 2006 and 2020, excluding those with disease in both body cavities (bicavitary). Survival analyses used the 526 who received CRS/HIPEC.
• Exposure: Asbestos exposure was not studied. The factors studied were sex, and age as a proxy for menopausal status (40 or younger versus 60 or older; ages 41 to 59 excluded from this part), among patients treated with CRS/HIPEC.
• Main results:
  • Of 1868 patients, 1012 (54.2%) were male and 526 (28.2%) received CRS/HIPEC.
  • On multivariable analysis, male sex was associated with receiving CRS/HIPEC (OR 1.054, p = 0.015). Patients at nonacademic hospitals were less likely to receive it than those at academic centers (OR 0.798, p less than 0.001).
  • Among female patients under 75 with a Charlson-Deyo comorbidity score of 0 or 1 (n = 692), 197 (28.5%) underwent CRS/HIPEC.
  • Among the 526 patients who received CRS/HIPEC, female sex was associated with better overall survival than male sex on multivariable Cox regression (adjusted HR 0.635, 95% CI 0.452 to 0.890, p = 0.008).
  • In the age-stratified CRS/HIPEC subgroup (41 premenopausal females, 76 postmenopausal females, 31 younger males, 154 older males), median survival was not reached for premenopausal females at 175 months. Median survival was 66.6 months for postmenopausal females (p = 0.001), 116.9 months for younger males (p = 0.014) and 39.1 months for older males (p less than 0.001).
  • On multivariable Cox regression with premenopausal females as the comparison group, risk of death was higher for postmenopausal females (HR 4.125, 95% CI 1.587 to 10.72, p = 0.004), older males (HR 6.012, 95% CI 2.386 to 15.15, p less than 0.001) and younger males (HR 4.174, 95% CI 1.485 to 11.73, p = 0.007).
  • Among patients 40 or younger, female sex was the only significant predictor of overall survival (HR 0.267, p = 0.012). Among patients 60 or older, female sex did not reach statistical significance (HR 0.676, p = 0.061).
  • Year of diagnosis was not a significant predictor of receiving CRS/HIPEC (p = 0.62).
• The authors' conclusion: The authors concluded that the female survival advantage after CRS/HIPEC may be partly driven by premenopausal women, suggesting that sex hormones may play a role in peritoneal mesothelioma. They called for prospective, multicenter studies with biologic markers of hormone status.
• Limitations the authors state:
  • A retrospective database study carries a risk of selection bias and unmeasured confounding.
  • Some patients who received CRS/HIPEC may have been missed because they were not coded as having received intraoperative chemotherapy.
  • Menopausal status was inferred from age only. Direct measures, reproductive history and hormone use were not available, which may cause misclassification.
  • Ki-67 and thrombocytosis, which are high-risk criteria that influence treatment decisions, were not available.
  • Details of the HIPEC treatment, such as drug selection and dosing, were not available.
  • Cause of death was not recorded, so only overall survival could be analyzed. Because older patients die more often of non-cancer causes, this could bias the results.
  • The database includes only Commission on Cancer accredited hospitals, so findings may be less generalizable to nonacademic or lower-volume centers.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Epithelioid, Peritoneal Mesothelioma, Cytoreductive Surgery, HIPEC, Mesothelioma, Overall Survival, Odds Ratio, Hazard Ratio.

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