Perioperative Outcomes of Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy Following Neoadjuvant Systemic Therapy for High-Volume Peritoneal Mesothelioma

Background: The role and optimal sequencing of systemic therapy in patients with high-volume peritoneal mesothelioma (PeM) undergoing curative-intent cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) remains unclear. We compared perioperative outcomes in patients undergoing upfront CRS/HIPEC (U-CRS) versus those receiving neoadjuvant therapy (NAT). Methods: This single-institution retrospective study included patients with PeM (2009-2023) who underwent CRS/HIPEC with a peritoneal carcinomatosis index (PCI) > 20. Primary outcomes were prolonged operative time (OT), defined as > 75th percentile for the study cohort, and 90-day postoperative complications. Secondary outcomes included complete cytoreduction with CC-0 score, recurrence-free survival (RFS), and overall survival (OS). Results: Of 45 patients, 14 (31 %) underwent U-CRS and 31 (69 %) received NAT. Most NAT patients (94 %) were treated with a platinum agent and pemetrexed, with or without bevacizumab, for a median of 6 cycles. Median PCI was similar between groups (U-CRS: 28; NAT: 27; p = 0.73). Median OT was 572 min (U-CRS) vs. 645 min (NAT; p = 0.17). Grade III-V complications occurred in 50 % of U-CRS vs. 32 % of NAT patients (p = 0.42). NAT was not independently associated with prolonged OT or severe complications on multivariable analyses. Rates of CC-0 resection, RFS, and OS were similar between groups. Conclusions: NAT is feasible and safe in patients with high-volume PeM undergoing CRS/HIPEC, without negatively affecting perioperative outcomes. The neoadjuvant setting offers a valuable platform for investigating novel therapies aimed at improving long-term outcomes in PeM. Synopsis: Neoadjuvant systemic therapy before CRS/HIPEC for high-volume peritoneal mesothelioma is feasible and safe with similar operative times and complication rates as upfront surgery, supporting its use as a platform to evaluate novel therapies to improve long-term outcomes in peritoneal mesothelioma.