Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC): Why it will Transform Cancer Surgery

Abstract Pressurized intraperitoneal aerosol chemotherapy (PIPAC) represents an innovative method for delivering chemotherapy directly into the abdominal cavity, offering a targeted, effective, and less toxic treatment option for patients with nonresectable peritoneal metastasis (PM). PIPAC is increasingly adopted due to its benefits over traditional therapies, including enhanced drug penetration, reduced systemic toxicity, and improved efficacy in chemoresistant PM. Performed laparoscopically, PIPAC is minimally invasive, often outpatient, and well-tolerated, preserving patients’ quality of life. So far, PIPAC has been mainly used in advanced PM from ovarian, gastric, and colorectal cancers, where it can be effective even after other treatments have failed. The repeatable nature of PIPAC offers opportunities for maintenance therapy and long-term disease control. A recent meta-analysis of PIPAC studies reported a 4% nonaccess rate and 39% of patients completing three or more cycles, with only 4% experiencing severe toxicities. Pathological responses were observed in 68% of cases, indicating reliable efficacy. A first randomized trial showed PIPAC’s superiority in objective response rates and quality of life compared with intravenous chemotherapy for platinum-resistant ovarian cancer. Research in PIPAC is dynamic and multidisciplinary, aiming to refine the technique, minimize side effects, and expand its applicability to various cancers. Studies focus on the efficacy of aerosolized drug delivery, including nanoparticles and RNA-based therapies, which offer targeted treatment options with promising therapeutic potential. Innovations such as electrostatic precipitation PIPAC (ePIPAC) combine enhanced drug distribution with increased tissue penetration, representing significant advancements in PM treatment. Future developments will focus on optimizing aerosol characteristics, drug formulations, and personalized medicine approaches.