Sex-Specific Patterns of Asbestos Exposure and Prognostic Biomarkers in Surgically Treated Pleural Mesothelioma: A Retrospective Cohort Study

Background/Objectives: Sex-based differences in asbestos exposure and tumor biology in pleural mesothelioma (PM) remain incompletely characterized. As an expert tertiary center, we sought to systematically characterize asbestos exposure by sex and assess biomarker prognostic relevance in surgically treated pleural mesothelioma. Methods: We conducted a retrospective, single-center cohort encompassing all patients who underwent surgical intervention for PM at our institution. Demographic characteristics, asbestos exposure history, tumor biomarker profiles, and survival outcomes were extracted from this database and supplemented by review of the electronic medical record. Sex differences in asbestos exposure and biomarker expression were assessed using Fisher’s exact test on an available-case basis, while logistic regression was used to identify predictors of documented asbestos exposure. Overall survival was estimated using Kaplan–Meier analysis; independent associations between biomarkers and mortality were determined via multivariable Cox proportional hazards models adjusted for age, sex, and histological subtype. Results: Between 2015 and 2024, 106 patients (75% males) underwent surgical intervention for PM, with a median follow-up of 4.4 years. The mean age at surgery was 67.5 years (Standard Deviation [SD], 11). The cohort predominantly consisted of patients with epithelioid histology (n = 86, 81%), followed by biphasic (n = 16, 15%), and sarcomatoid (n = 4, 4%) subtypes. Thirty (28.3%) were alive at last follow-up. Median overall survival was 15.6 months (95% Confidence Interval [CI], 13.8–25.4 months), and 5-year survival was 17.8%. Of 92 patients with available exposure data, 66 (72%) had documented exposure histories. Although most of these exposures were occupational (46, 78%), a striking disparity was observed between occupational exposures in males vs. females (44 [86%] vs. 2 [25%]; n = 8 classifiable females; p < 0.001). Multivariable analysis demonstrated that male sex was associated with increased odds of asbestos exposure (Adjusted Odds Ratio [ORadj], 5.45; 95% Confidence Interval [CI], 1.90–16.35). PD-L1, Ki-67, or BAP1 expression were not associated with sex, age, or asbestos exposure. High Ki-67 (>15%) and PD-L1 (>15%) were associated with a four-fold and three-fold increased risk of mortality (Hazard Ratioadj [HRadj], 4.33 [95% CI, 1.85–10.13] and HRadj, 2.80 [95% CI, 1.39–5.64], respectively), whereas BAP1 loss was not (HRadj, 0.80; 95% CI, 0.45–1.44). Conclusions: Our findings underscore the potential value of sex-sensitive screening protocols that more comprehensively assess non-occupational asbestos exposure pathways and offer additional evidence regarding the prognostic relevance of PD-L1, Ki-67, and BAP1 in surgical patients.