Navigating the Foggy Landscape of Epithelioid Peritoneal Mesothelioma: A Proposed Standardized Institutional...

Purpose: Diffuse malignant peritoneal mesothelioma is a rare disease requiring management in specialized referral centers. We report our institutional experience with epithelioid diffuse malignant peritoneal mesothelioma, focusing on a standardized treatment algorithm and on pre-operative cisplatin-pemetrexed as a bridge to cytoreductive surgery and HIPEC. Methods: Consecutive patients treated between 2016 and 2024 were retrospectively reviewed. Treatment allocation was based on diagnostic laparoscopy, PCI assessment, and multidisciplinary evaluation. Patients with technically resectable disease underwent upfront CRS-HIPEC, whereas borderline or unresectable patients received cisplatin-pemetrexed followed by systematic reassessment. Results: Forty-three patients were included; 19 underwent CRS-HIPEC, including 8 after pre-operative chemotherapy, and 24 received medical management alone. Curative-intent cytoreduction (CC-0/1) was achieved in all operated patients, with no 30-day mortality. No statistically significant difference in overall survival was detected between upfront and conversion surgery patients in this small cohort. Higher PCI and Ki-67 were independently associated with worse overall survival. Conclusions: A structured multidisciplinary pathway may support tailored treatment selection in epithelioid diffuse malignant peritoneal mesothelioma. In selected responders, cisplatin-pemetrexed may act as a bridge to surgery, although larger studies are required to validate this strategy.