Ismaili N. Shifting paradigm in locally advanced resectable gastric and gastroesophageal junction cancers. World J Gastrointest Oncol 2026; 18(2): 113150 [DOI: 10.4251/wjgo.v18.i2.113150]
Corresponding Author of This Article
Nabil Ismaili, MD, Associate Professor, Chief Physician, Department of Medical Oncology, Mohammed VI Faculty of Medicine, Mohammed VI University of Sciences and Health, Boulevard Mohammed Taieb Naciri, Commune Hay Hassani, Casablanca 20000, Morocco. ismailinabil@yahoo.fr
Research Domain of This Article
Oncology
Article-Type of This Article
Letter to the Editor
Open-Access Policy of This Article
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/
World J Gastrointest Oncol. Feb 15, 2026; 18(2): 113150 Published online Feb 15, 2026. doi: 10.4251/wjgo.v18.i2.113150
Shifting paradigm in locally advanced resectable gastric and gastroesophageal junction cancers
Nabil Ismaili
Nabil Ismaili, Department of Medical Oncology, Mohammed VI Faculty of Medicine, Mohammed VI University of Sciences and Health, Casablanca 20000, Morocco
Author contributions: Ismaili N was responsible for conceptualization, methodology and software, validation, formal analysis and investigation, resources, data curation, writing original draft, review and editing and visualization.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Nabil Ismaili, MD, Associate Professor, Chief Physician, Department of Medical Oncology, Mohammed VI Faculty of Medicine, Mohammed VI University of Sciences and Health, Boulevard Mohammed Taieb Naciri, Commune Hay Hassani, Casablanca 20000, Morocco. ismailinabil@yahoo.fr
Received: August 18, 2025 Revised: October 28, 2025 Accepted: November 27, 2025 Published online: February 15, 2026 Processing time: 170 Days and 15.4 Hours
Abstract
Gastric cancer (GC) is the fifth most common cancer and the fifth leading cause of cancer-related mortality worldwide. The management of resectable locally advanced GC evolved with the introduction of adjuvant chemoradiotherapy in some regions, notably following the INT-0116 trial. A subsequent major advance was perioperative chemotherapy with epirubicin, cisplatin, and fluorouracil, which significantly improved 5-year overall survival compared to surgery alone. More recently, the fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) regimen demonstrated superior outcomes compared to epirubicin, cisplatin, and fluorouracil. Despite this advancement, nearly half of all patients (46%) experience disease recurrence within three years, underscoring a significant unmet need. In a recent real-world study by Wang et al, which assessed perioperative sintilimab plus oxaliplatin and S-1 chemotherapy vs chemotherapy alone in non-metastatic GC, the authors reported significantly improved pathological response rates and overall survival with the combination. Additionally, the safety profile showed a lower frequency of high-grade adverse events. However, this study has limitations, including its retrospective design and the use of a chemotherapy backbone (oxaliplatin and S-1) considered less effective than FLOT based on phase III evidence. Recent data from the phase III MATTERHORN trial support the addition of durvalumab to FLOT, showing significant improvements in pathological complete response and event-free survival. Based on the cumulative evidence, adding immunotherapy to perioperative chemotherapy improves outcomes for patients with resected GC and may constitute a new standard of care once confirmatory data mature and regulatory approvals are granted.
Core Tip: The recent real-world study by Wang et al adds to the growing evidence that perioperative sintilimab combined with oxaliplatin and S-1 chemotherapy improves pathological response and overall survival in non-metastatic gastric cancer, with a manageable safety profile. However, the conclusions are tempered by the study’s retrospective design, limited power, and the use of a potentially suboptimal chemotherapy backbone. Crucially, this data aligns with the positive results of the large phase III MATTERHORN trial, solidifying the paradigm shift. The collective evidence now strongly suggests that adding immunotherapy to perioperative chemotherapy enhances cure rates for locally advanced resectable gastric and gastroesophageal junction cancers, establishing this combination as a new standard of care.
