Efficacy of Preventive Pressurized Intraperitoneal Aerosol Chemotherapy in Patients With Locally Advanced Gastric Cancer: Protocol for a Prospective Controlled Trial

Abstract

Background: Gastric cancer is a serious health issue both globally and in Kazakhstan. Worldwide, gastric cancer ranks fifth in incidence, with the highest rates reported in East Asia, the Andes of South America, and Eastern Europe, while the lowest rates are reported in North America, Northern Europe, Africa, and Southeast Asia. Over 70% of the cases occur in resource-limited countries. In Kazakhstan, gastric cancer ranks third in morbidity and second in mortality, representing a serious clinical and social problem. Annually, 1600 deaths from malignant gastric neoplasms are registered. Peritoneal metastasis is considered one of the most severe complications of gastric cancer and has long been regarded as its terminal stage. The average life expectancy of patients with peritoneal metastasis is only 3-6 months, reflecting a high mortality rate and the limited efficacy of current treatments.

Objective: We hypothesize that the prophylactic use of pressurized intraperitoneal aerosol chemotherapy (PIPAC) may reduce the incidence of peritoneal metastasis. The aim of this study is to evaluate the incidence of peritoneal metastasis following prophylactic PIPAC in patients with gastric cancer. The primary goal of this research is to evaluate whether adding prophylactic PIPAC to standard treatment before neoadjuvant chemotherapy can reduce the incidence of peritoneal metastasis in patients with locally advanced gastric cancer.

Methods: This study is a single-center nonrandomized controlled trial with a planned enrollment of 160 patients. All participants will be included in one of the 2 groups: intervention group (PIPAC + perioperative chemotherapy + gastrectomy with D2 lymphadenectomy) or control group (perioperative chemotherapy + gastrectomy with D2 lymphadenectomy). The primary end point is the incidence of peritoneal metastasis, and the secondary end points are overall survival, recurrence-free survival, treatment-related adverse events, and personal satisfaction.

Results: As of September 2025, this study is funded and recruiting; 102 participants have already been enrolled. Recruitment is planned to be performed between January 2025 and December 2026. No interim analyses have been performed; primary results are planned for Q1 2027. The manuscript is expected to be published by Q4 2027.

Conclusions: Compared to standard chemotherapy, PIPAC has been reported to significantly improve survival rates in patients with peritoneal metastasis of gastric origin. We suggest that the neoadjuvant use of PIPAC may reduce the incidence of peritoneal metastasis and improve long-term survival outcomes. The results of our study will provide key information on the practicality and viability of PIPAC as a prophylactic technique for preventing the progression of gastric cancer.

Trial registration: ClinicalTrials.gov NCT06784765; https://clinicaltrials.gov/study/NCT06784765.

International registered report identifier (irrid): PRR1-10.2196/78053.

Keywords: HIPEC; PIPAC; chemotherapy; gastric cancer; hyperthermic intraperitoneal chemotherapy; intraperitoneal treatment; oncology; peritoneal metastasis; pressurized intraperitoneal aerosol chemotherapy.

Figure 1

Study design. AdjCTx: adjuvant chemotherapy; cyt: cytology; FLOT: fluorocil, leucovorin, oxaliplatin, docetaxel; GC: gastric cancer; NeoAdjCTx: neoadjuvant chemotherapy; PC: peritoneal carcinomatosis; PIPAC: pressurized intraperitoneal aerosol chemotherapy.