# Intraperitoneal Chemotherapy Strategies in Pancreatic Ductal Adenocarcinoma: A Systematic Review of Hyperthermic Intraperitoneal Chemotherapy, Normothermic Intraperitoneal Chemotherapy, and Pressurized Intraperitoneal Aerosol Chemotherapy

## TL;DR

This paper reviews different ways to deliver chemotherapy directly to the abdomen for pancreatic cancer, aiming to improve outcomes and reduce side effects.

## Contribution

The study systematically evaluates three intraperitoneal chemotherapy strategies for pancreatic cancer and identifies their potential benefits and limitations.

## Key findings

- Intraperitoneal chemotherapy strategies showed acceptable safety and feasibility in selected patients.
- CRS + HIPEC provided multi-year survival in patients with complete cytoreduction of peritoneal metastases.
- NIPEC/IP-PTX and PIPAC mainly offer symptom control and disease stabilization rather than curative outcomes.

## Abstract

Pancreatic cancer often spreads to the lining of the abdomen, leading to severe symptoms and very limited treatment options. Standard chemotherapy does not reach this area well, which is one reason outcomes remain poor. This review explores treatments that deliver cancer medicines directly into the abdominal cavity, allowing much higher local drug levels with fewer whole-body side effects. These approaches include heated chemotherapy during surgery, repeated liquid chemotherapy through a small port, and aerosolized chemotherapy given with minimally invasive procedures. By examining the safety, benefits, and limitations of these methods, our goal is to understand which patients may benefit most and how these treatments could be combined with standard care. Our findings may help guide future research, improve patient selection, and support the development of clinical trials focused on better options for patients with abdominal spread of pancreatic cancer.

Background: Peritoneal metastasis represents an aggressive disease pattern in pancreatic ductal adenocarcinoma (PDAC), traditionally associated with poor survival and limited therapeutic options. Emerging intraperitoneal chemotherapy strategies—including hyperthermic intraperitoneal chemotherapy (HIPEC), normothermic intraperitoneal paclitaxel (NIPEC/IP-PTX), and pressurized intraperitoneal aerosol chemotherapy (PIPAC)—have been investigated to improve local tumor control and survival outcomes. Methods: We systematically reviewed published studies evaluating HIPEC, NIPEC/IP-PTX, and PIPAC in PDAC, including adjuvant, cytoreductive, and palliative settings. Study characteristics, feasibility, perioperative outcomes, oncologic outcomes, and risk of bias were analyzed. Results: Across modalities, intraperitoneal treatment strategies demonstrated acceptable feasibility and safety profiles in appropriately selected patients. Adjuvant HIPEC following pancreatectomy showed reduced local–regional recurrence signals in limited cohorts. CRS + HIPEC among patients with isolated peritoneal metastases yielded encouraging multi-year survival in highly selected candidates achieving complete cytoreduction. NIPEC/IP-PTX demonstrated favorable ascites control, symptom relief, and potential conversion to resection in select patients. PIPAC was primarily used in unresectable, heavily pretreated, palliative peritoneal metastasis settings, with goals centered on disease stabilization, histologic regression, and symptom control rather than curative intent. Conclusions: Intraperitoneal chemotherapy strategies in PDAC appear feasible with signals of meaningful clinical benefit in select settings. While CRS + HIPEC may benefit carefully selected metastatic patients, NIPEC/IP-PTX and PIPAC hold value primarily in symptom control and disease stabilization. Larger prospective trials are needed to define patient selection, optimize treatment protocols, and clarify survival benefit.