D'Acapito F, Framarini M, Morgagni P, Di Pietrantonio D, Vittimberga G, Zucchini V, Ercolani G. Advancing gastric cancer treatment: A comprehensive review of hyperthermic intraperitoneal chemotherapy’s role and outcomes. World J Clin Oncol 2025; 16(9): 109034 [PMID: 41024842 DOI: 10.5306/wjco.v16.i9.109034]
Corresponding Author of This Article
Fabrizio D'Acapito, PhD, Consultant, Department of General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Via Carlo Forlanini 34, Forli 47121, Emilia-Romagna, Italy. fabrizioda@gmail.com
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Surgery
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Systematic Reviews
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Sep 24, 2025 (publication date) through Oct 25, 2025
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World Journal of Clinical Oncology
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D'Acapito F, Framarini M, Morgagni P, Di Pietrantonio D, Vittimberga G, Zucchini V, Ercolani G. Advancing gastric cancer treatment: A comprehensive review of hyperthermic intraperitoneal chemotherapy’s role and outcomes. World J Clin Oncol 2025; 16(9): 109034 [PMID: 41024842 DOI: 10.5306/wjco.v16.i9.109034]
World J Clin Oncol. Sep 24, 2025; 16(9): 109034 Published online Sep 24, 2025. doi: 10.5306/wjco.v16.i9.109034
Advancing gastric cancer treatment: A comprehensive review of hyperthermic intraperitoneal chemotherapy’s role and outcomes
Fabrizio D'Acapito, Massimo Framarini, Paolo Morgagni, Daniela Di Pietrantonio, Giovanni Vittimberga, Valentina Zucchini, Giorgio Ercolani
Fabrizio D'Acapito, Massimo Framarini, Paolo Morgagni, Daniela Di Pietrantonio, Giovanni Vittimberga, Valentina Zucchini, Giorgio Ercolani, Department of General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forli 47121, Emilia-Romagna, Italy
Giorgio Ercolani, Department of Medical and Surgical Sciences, University of Bologna, Bologna 40126, Emilia-Romagna, Italy
Author contributions: D’Acapito F wrote the original draft; Framarini M and Morgagni P contributed to conceptualization, writing, reviewing and editing; Di Pietrantonio D, Vittimberga G, Zucchini V and Ercolani G participated in drafting the manuscript; D’Acapito F, Framarini M, Morgagni P, Di Pietrantonio D, Vittimberga G and Zucchini V done studies initial screening; all authors have read and approved the final version of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Fabrizio D'Acapito, PhD, Consultant, Department of General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Via Carlo Forlanini 34, Forli 47121, Emilia-Romagna, Italy. fabrizioda@gmail.com
Received: April 28, 2025 Revised: May 26, 2025 Accepted: August 8, 2025 Published online: September 24, 2025 Processing time: 148 Days and 9.9 Hours
Abstract
BACKGROUND
Peritoneal metastases (PM) represent the most frequent and lethal form of dissemination in advanced gastric cancer (GC), with limited efficacy of systemic chemotherapy [median overall survival (OS): 2-9 months]. Over the past decades, hyperthermic intraperitoneal chemotherapy (HIPEC), often combined with cytoreductive surgery (CRS), has emerged as a locoregional strategy to improve peritoneal disease control. Retrospective studies have suggested promising survival benefits (median OS: 18.8 months); however, conflicting results from prospective trials have limited its widespread adoption. This systematic review hypothesizes that selected patients with advanced or high-risk GC may benefit from HIPEC and evaluates whether such benefits have been confirmed in recent prospective evidence.
AIM
To evaluate the role and outcomes of HIPEC in advanced and high-risk GC through a systematic review of prospective trials.
METHODS
A systematic review of prospective randomized and controlled clinical trials (2010-2024) was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. Studies were selected from PubMed, Cochrane, Scopus, and ClinicalTrials.gov. No geographical restrictions were applied in the search process. Eligible studies included patients with advanced GC (T3+, positive peritoneal cytology/PM) receiving HIPEC in either therapeutic or prophylactic settings. Exclusion criteria included retrospective studies, single-arm trials, and those lacking survival outcomes. Risk of bias was assessed using Risk of Bias 2.0 and Risk of Bias in Non-Randomized Studies of Interventions tools; sensitivity and heterogeneity analyses were also conducted.
RESULTS
Thirteen prospective studies (eight therapeutic, five prophylactic) were included. In therapeutic settings, CRS combined with HIPEC yielded a median OS of 11-24.9 months vs 4-6 months with systemic therapy alone. Completeness of cytoreduction (CC-0) was achieved in 67.3% of cases, and associated with improved disease-free survival. In prophylactic settings, HIPEC significantly reduced peritoneal recurrence, particularly in T4 tumors. Sensitivity analyses confirmed robustness of findings, though benefit was driven by a few key trials. Heterogeneity was moderate across studies; lack of standardized HIPEC protocols and patient selection criteria limited comparability.
CONCLUSION
HIPEC may improve survival and reduce recurrence in selected GC patients, particularly those with low peritoneal burden and CC-0 resection. Further standardization and prospective trials are needed.
Core Tip: This systematic review evaluates prospective trials assessing hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer (GC). Therapeutically, HIPEC combined with cytoreductive surgery improves survival in selected patients with peritoneal metastases. Prophylactically, HIPEC reduces peritoneal recurrence after curative gastrectomy in high-risk patients. While promising, outcomes are influenced by heterogeneity in protocols, chemotherapy regimens, and selection criteria. Completeness of cytoreduction remains the strongest predictor of benefit. Future trials should standardize patient selection and HIPEC approaches to clarify its role within multimodal GC treatment strategies.
