Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) for Peritoneal Malignancies with Palliative and Bidirectional Intent

<b>Background</b>: PIPAC is an innovative treatment that delivers low-dose aerosolized chemotherapy into the abdominal cavity of patients with peritoneal surface malignancies (PSMs). However, its role in the multimodal management of PSMs is unclear. <b>Methods</b>: We retrospectively analyzed data from 64 patients who underwent PIPAC for PSMs of a primary or secondary origin between June 2020 and December 2024 (median age of 64 years). Primary tumor sites included gastric (42.2%), colorectal (23.4%), ovarian cancer (21.9%), and others (12.5%). The median PCI was 15 (IQR 9-25), with ascites present in 60.9% of cases and a positive cytology in 48.4%. <b>Results</b>: A total of 82 PIPAC sessions were performed in 64 patients. The mean operation time was 96 min. Severe adverse events, defined as the Common Terminology Criteria for Adverse Events (CTCAE) of a grade ≥ 2, occurred in four patients (6.2%). The median hospital stay was 3 days, and systemic chemotherapy was resumed within 14 days after the procedure in 27 patients. Among the entire cohort, 37.5% received bidirectional therapy and 62.5% received palliative treatment, with a lower peritoneal cancer index (PCI) in the bidirectional group (9.5 vs. 23). The median overall survival (OS) was 32 months from diagnosis. Sixteen patients (25%) underwent two or more PIPAC sessions and showed an advantage in survival compared to patients who underwent only one procedure (3-year OS: 63.2% vs. 38.4%, <i>p</i> 0.030). Conversion surgery was achieved in 34.4%. Patients treated with a bidirectional intent demonstrated a longer OS (3-year: 66.0% vs. 33.9%, <i>p</i> 0.011). Colorectal and ovarian tumors exhibited better long-term outcomes compared to gastric cancer. <b>Conclusions</b>: PIPAC is a promising treatment for PSMs, with a low morbidity rate. Its favorable safety and short interval to systemic therapy resumption support its use as part of a bidirectional strategy.