COMPREHENSIVE TREATMENT OF LOCALLY ADVANCED AND METASTATIC GASTRIC CANCER: THE ROLE OF NEOADJUVANT INTRA-ARTERIAL CHEMOTHERAPY

Abstract

Introduction: Stage III-IV gastric cancer (GC) is characterized by high rates of locoregional recurrence and distant metastasis, resulting in a poor prognosis despite modern systemic chemotherapy regimens. Although triple- and quadruple-drug perioperative regimens have improved outcomes, a significant proportion of patients still exhibit low tumor resectability and limited pathological complete response (pCR) rates. Consequently, identifying methods that locally increase cytostatic agent concentrations within the tumor lesion while minimizing systemic toxicity is essential. Objective: To evaluate contemporary therapeutic strategies for locally advanced and metastatic GC, with a specific focus on the clinical role of neoadjuvant intra-arterial chemotherapy (IACT) and its impact on achieving R0 resection margins and enhancing pathological response rates, including the pCR rate. Methods: We conducted a comprehensive literature search in PubMed/MEDLINE, Scopus, Web of Science, and eLIBRARY.ru from 2014 to 2025. We used the following Medical Subject Headings (MeSH) keywords and their Russian-language equivalents: "gastric cancer", "neoadjuvant chemotherapy", "regional chemotherapy", "intra-arterial chemotherapy", "hyperthermic intraperitoneal chemotherapy", "conversion therapy", "perioperative treatment", and "hepatic metastasis". Of the 642 publications identified, we excluded duplicates and irrelevant works, leaving 48 articles for final analysis. We prioritized randomized controlled trials, prospective cohort studies, and meta-analyses. Results: Neoadjuvant IACT showed higher rates of significant tumor regression and pCR than isolated systemic chemotherapy. Multiple series reported a higher proportion of R0 resections, including cases initially classified as unresectable disease. The systemic toxicity profile was generally no higher than that observed with intravenous cytostatics; however, rigorous monitoring for localized vascular complications remains necessary. Conclusion: Neoadjuvant IACT is a promising component of multimodal treatment that can increase rates of radical surgery and improve locoregional disease control. Further validation of its long-term efficacy requires standardized, prospective studies with unified patient selection criteria. Keywords: Gastric cancer, neoadjuvant therapy, intra-arterial chemotherapy, regional chemotherapy, conversion treatment, pathological response, resectability