Background:
Sex-based differences in asbestos exposure and tumor biology in pleural mesothelioma remain
incompletely characterized. While males commonly report long, occupational asbestos exposure histories,
females frequently present with non-occupational or unknown exposure histories. In parallel, the
prognostic significance of key tumor biomarkers remains heterogeneous across studies, with PD-L1 and
Ki-67 as the only two biomarkers consistently associated with increased mortality, whereas the prognostic
value of BAP1 remains inconsistent and largely evaluated in chemotherapy-treated cohorts.

Objectives:
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 cohort study using the Department of Thoracic Surgery’s Prospectively
Maintained Database (DTS), encompassing all patients who underwent surgical intervention for pleural
mesothelioma at the Icahn School of Medicine at Mount Sinai between 2015 and 2024. Patients were
identified using procedural codes, primary diagnosis, and EMR review. Demographic characteristics,
asbestos exposure history, tumor biomarker profiles, and survival outcomes were extracted. Tumor
biomarker data were available for 19 biomarkers; analyses focused on PD-L1, Ki-67, and BAP1 based on
their reported prognostic significance. Survival status and dates of death or last follow-up were obtained
from the EMR and supplemented by publicly available obituary data. Differences in asbestos exposure by
sex were assessed using multivariable regression. Overall survival was estimated using Kaplan-Meier
analysis, and biomarker associations with mortality evaluated using multivariable Cox proportional
hazards models.

Results:
Between 2015 and 2024, 113 patients (73% males) underwent surgical intervention for pleural
mesothelioma, of whom 36 patients (32%) were alive at last follow-up. Sixty-eight of 97 patients (70%)
with available exposure data had likely previous asbestos exposure. The mean age was 66.5 years
(Standard Deviation [SD], 12.3). Median overall survival was 478 days (95% Confidence Interval [CI],
426-781 days), and 5-year mortality was 90.2%.

Male sex was associated with increased odds of likely asbestos exposure (Odds Ratio [OR], 5.27; 95%
CI, 1.97–14.8), as was increasing age in univariable analysis (OR, 1.04 per year; 95% CI, 1.01–1.08). In
multivariable analyses, PD-L1, Ki-67, or BAP1 expression was not associated with sex, age, or asbestos
exposure. In multivariable Cox proportional hazard models adjusting for age and sex, PD-L1 (>15%) and
Ki-67 (>15%) were associated with worse overall survival (Hazard Ratio [HR], 3.22 [95% CI, 1.64–6.33]
and HR, 5.25 [95% CI, 2.30–12.01], respectively), whereas BAP1 expression was not (HR, 1.20; 95% CI,
0.43–3.37).

Conclusions:
In this surgically treated cohort, we report asbestos exposure to be significantly less common among
female patients. We further confirm the adverse prognostic value of PD-L1 and Ki-67 expression for
surgically treated patients, while finding that BAP1 expression is not associated with survival for this
group. Future, larger studies should seek to evaluate if the impact of such prognostic biomarkers is
modulated by sex. Together, these findings clarify underreported sex-based differences in asbestos
exposure and refine the prognostic relevance of key biomarkers in surgically-treated pleural
mesothelioma.