Defining the role of endoscopic resection for esophageal gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that arise from the interstitial cells of Cajal and muscularis propria that can affect any part of the gastrointestinal (GI) tract from the esophagus to the anus. They most frequently affect the stomach and small intestine, accounting for 60% and 25% of cases, respectively (1). Esophageal GISTs (e-GISTs) are rarer, representing less than 1% of all GIST cases (2). Symptoms of GISTs vary depending on their location with most e-GISTs presenting with GI bleeding, early satiety, or dysphagia. Recognition of these tumors is important as they harbor potential for malignant transformation but can be mistaken for benign esophageal pathology.

To date, guidelines suggest that small, asymptomatic GISTs can be observed (3,4). Endoscopic ultrasound (EUS) has allowed clinicians to further stratify these lesions based on sonographic features with low-risk features as a relative indication for surveillance (5). If masses are greater than 2 centimeters (cm), symptomatic, or have high-risk EUS or biopsy features including irregular borders, cystic spaces, heterogenicity, or echogenic foci, definitive treatment is surgical resection (SR) (3). SR for gastric GISTs (g-GISTs) includes wedge, partial, or less likely total gastrectomy (6) whereas e-GISTs can be treated with enucleation or esophagectomy. These oncologic resections are adopted to ensure proper margins. If not amenable to upfront resection, tumors receive neoadjuvant imatinib to target c-KIT and platelet-derived growth factor receptor. Over the past decade, laparoscopic and robotic approaches have provided minimally-invasive surgical methods with endoscopic resection (ER) offering the potential to further decrease morbidity, hospital length of stay, and patient cost (7-9).

Zhou et al. reported in Surgical Endoscopy a series of 46 e-GIST and 366 g-GIST patients where they studied intrinsic tumor characteristics and outcomes after ER and SR (10). EUS analyses revealed that e-GISTs were larger, ulcerated and bled more, and had more cystic changes, heterogeneous echogenicity, and greater mitotic counts compared to their gastric counterparts. On uni- and multi-variate analysis of the e-GISTs, larger tumors (>5 cm), tumor bleeding, and mitotic counts ≥5/50 per high power field (HPF) portended worse overall survival (OS). Worrisome EUS features (e.g., heterogeneous appearance, cystic changes, lymphadenopathy) did not affect OS. A total of 22 e-GIST patients underwent ER (55%) with three patients receiving endoscopic submucosal dissection (ESD) and the other 19 submucosal tunneling ER (STER). Three lesions ruptured during ER (18%). Negative margins were achieved in 17 (77%) patients, and eight patients (36%) had an e-GIST-related cause of death within the study period of five years. Of the 18 e-GIST patients undergoing SR (45%), six patients had an unspecified “death-related complication” (33%). There was no statistically significant difference between the groups’ 5-year OS and recurrence rate. As such, the authors suggest that ER can be considered in patients with tumors smaller than 5 cm and mitotic counts <5/50 HPF, independent of EUS findings.

While these results are encouraging, the study has many limitations. This was conducted at a single institution with a small sample size; the authors admit the study was underpowered. The average tumor size treated by ER was significantly smaller than that of SR: 40% of tumors were ≥2 cm in ER whereas all were ≥2 cm in SR (P=0.001). Further, of the 16 high-risk e-GIST patients eligible for adjuvant therapy, only 10 (62.5%) received imatinib while the other 6 patients declined treatment. These conditions introduced selection bias and limited robust statistical comparisons; the lack of difference in survival outcomes may reflect tumor baseline differences rather than true resection efficacy. Previous work has shown that positive margins (R1) and tumor rupture contribute to higher recurrence risk (5,11). The authors report no recurrence with their 23% R1 rate in ER, and they do not describe their SR R1 or rupture rate. Current guidelines recommend risk-stratified surveillance lasting 5–10 years as it is known that recurrence drops steeply after a decade (12). Here, the authors potentially miss long-term oncologic consequences of tumor rupture and overestimate their oncologic safety due to insufficient follow-up intervals. Another limitation is proceduralist variability. We and others have found that surgeon and proceduralist experience is critical for patient outcomes (13-16). It is unclear if the same proceduralist performed both ER and SR, and with already low numbers of both ESD and STER, this ambiguity introduces uncertainty. Indeed, ESD and STER are similar in that both remove submucosal tumors but they are critically different in that ESD incises the mucosa directly over the tumor while STER maintains mucosal integrity by creating a tunnel between the muscularis propria and submucosa, decreasing risk of perforation (17).

A contemporary study by Zhu et al. found in their cohort of 23 e-GIST patients that patients who underwent ER (n=15, 65%) had smaller lesions and fewer complications by percentage compared to those who underwent SR (18). Statistical significance was not reported. Another retrospective study of 32 e-GIST patients reported negative margins in 72% of cases (n=23) (19). The complication rate was 25% with 5-year OS 100% and disease-free survival 90.6%. The mean tumor size was 2.1±1.9 cm, and the mitotic index was low (3.3±5.0/HPF), which fall in the “small” range of Zhou et al.’s analysis. These independent analyses point to ER as a potential alternative to SR for low-risk e-GISTs but longer follow-up intervals are required for adequate prognostication, and the outcomes observed may reflect baseline tumor characteristics.

ER for e-GISTs remains investigative, and no national guidelines have yet to include ER as a standard treatment option. This is, in part, because work on this topic is scarce, and periodic surveillance is widely adopted for lesions ≤2 cm as recommended by the National Comprehensive Cancer Network. The benefit of ER over SR and radiographic surveillance for small lesions is undefined, and there is a need for prospective and randomized comparative studies before broader adoption. Thirty-day mortality in esophagectomy is notoriously high with studies quoting up to 15% in elderly patients including esophageal leak, pulmonary embolism, and myocardial infarction (20). This forces the question of how to decrease resection complications. Across all published work remains a consistent theme: Bulkier tumors that exhibit high-risk characteristics should undergo SR or at least a hybrid approach for improved post-resection outcomes (21). As is the case with all cancer resections, accurate perioperative risk stratification is paramount to surgical management.

Evolving technology, including dedicated endoluminal robotic approaches, contributes to an ever-changing clinical landscape (22,23). Artificial intelligence (AI) is also part of this change with machine learning-assisted detection and diagnosis (24). In some centers, AI models are improving tumor detection rates with high sensitivity, questioning the utility of the traditional, more invasive four-quadrant biopsies (25). Similarly in gastric cancer, a multi-institutional model using over one million images outperformed expert endoscopists with a diagnostic accuracy of 95% (26). Ongoing work should utilize standardized post-resection surveillance protocols to provide long-term oncologic data and assess ER safety in e-GISTs.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Journal of Gastrointestinal Oncology. The article has undergone external peer review.

Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0205/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0205/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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References

1. Tran T, Davila JA, El-Serag HB. The epidemiology of malignant gastrointestinal stromal tumors: an analysis of 1,458 cases from 1992 to 2000. Am J Gastroenterol 2005;100:162-8. [Crossref] [PubMed]
2. Judson I, Jones RL, Wong NACS, et al. Gastrointestinal stromal tumour (GIST): British Sarcoma Group clinical practice guidelines. Br J Cancer 2025;132:1-10. [Crossref] [PubMed]
3. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Gastrointestinal Stromal Tumors. [Epub 2026 Jan 13]. Available online: https://www.nccn.org/professionals/physician_gls/pdf/gist.pdf
4. Hirota S, Tateishi U, Nakamoto Y, et al. English version of Japanese Clinical Practice Guidelines 2022 for gastrointestinal stromal tumor (GIST) issued by the Japan Society of Clinical Oncology. Int J Clin Oncol 2024;29:647-80. [Crossref] [PubMed]
5. Casali PG, Blay JY, Abecassis N, et al. Gastrointestinal stromal tumours: ESMO-EURACAN-GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2022;33:20-33. [Crossref] [PubMed]
6. ASGE Standards of Practice Committee. The role of endoscopy in the management of premalignant and malignant conditions of the stomach. Gastrointest Endosc 2015;82:1-8. [PubMed]
7. de'Angelis N, Brunetti F, Felli E, et al. Laparoscopic versus open gastric wedge resection for primary gastrointestinal tumors: clinical outcomes and health care costs analysis. Surg Laparosc Endosc Percutan Tech 2015;25:143-6. [Crossref] [PubMed]
8. Vogli S, Papadakos SP, Argyrou A, et al. Expanding the role of endoscopic resection in esophageal gastrointestinal stromal tumors: Insights and challenges. World J Gastroenterol 2025;31:106441. [Crossref] [PubMed]
9. Libânio D, Pimentel-Nunes P, Bastiaansen B, et al. Endoscopic submucosal dissection techniques and technology: European Society of Gastrointestinal Endoscopy (ESGE) Technical Review. Endoscopy 2023;55:361-89. [Crossref] [PubMed]
10. Zhou Y, Peng R, Chen X, et al. The feasibility of endoscopic resection for esophageal gastrointestinal stromal tumor. Surg Endosc 2025;39:3718-26. [Crossref] [PubMed]
11. Hiki N, Nunobe S. Laparoscopic endoscopic cooperative surgery (LECS) for the gastrointestinal tract: Updated indications. Ann Gastroenterol Surg 2019;3:239-46. [Crossref] [PubMed]
12. Joensuu H, Martin-Broto J, Nishida T, et al. Follow-up strategies for patients with gastrointestinal stromal tumour treated with or without adjuvant imatinib after surgery. Eur J Cancer 2015;51:1611-7. [Crossref] [PubMed]
13. Adam MA, Moris D, Behrens S, et al. Hospital Volume Threshold for the Treatment of Retroperitoneal Sarcoma. Anticancer Res 2019;39:2007-14. [Crossref] [PubMed]
14. Conroy PC, Calthorpe L, Lin JA, et al. Determining Hospital Volume Threshold for Safety of Minimally Invasive Pancreaticoduodenectomy: A Contemporary Cutpoint Analysis. Ann Surg Oncol 2022;29:1566-74. [Crossref] [PubMed]
15. van der Merwe SW, van Wanrooij RLJ, Bronswijk M, et al. Therapeutic endoscopic ultrasound: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2022;54:185-205. [Crossref] [PubMed]
16. Zhang M, Wu S, Xu H. Comparison Between Submucosal Tunneling Endoscopic Resection (STER) and Other Resection Modules for Esophageal Muscularis Propria Tumors: A Retrospective Study. Med Sci Monit 2019;25:4560-8. [Crossref] [PubMed]
17. Krishnamoorthy A, Griffiths EA. Endoscopic resection of oesophageal gastrointestinal stromal tumours: Promise, pitfalls and the path forward. World J Gastroenterol 2025;31:110448. [Crossref] [PubMed]
18. Zhu S, Guo C, Zhang J, et al. Optimal management options for esophageal gastrointestinal stromal tumors (E-GIST). Eur J Surg Oncol 2024;50:108527. [Crossref] [PubMed]
19. Xu EP, Qi ZP, Zhang JW, et al. Endoscopic treatment outcome of oesophageal gastrointestinal stromal tumours. World J Gastroenterol 2025;31:102393. [Crossref] [PubMed]
20. Theiss L, Contreras CM. Gastrointestinal Stromal Tumors of the Stomach and Esophagus. Surg Clin North Am 2019;99:543-53. [Crossref] [PubMed]
21. Foroutani L, Ashraf Ganjouei A, Wang J, et al. Robotic-Assisted Endoluminal Resection of Gastroesophageal Junction Leiomyoma with Transoral Specimen Extraction: Technique, Outcome, and Safety. Ann Surg Oncol 2025;32:1218-9. [Crossref] [PubMed]
22. Shah D, Tesfai FM, Boal M, et al. Evaluation of current and emerging endoluminal robotic platforms using the IDEAL framework. Minim Invasive Ther Allied Technol 2025;34:253-66. [Crossref] [PubMed]
23. Tada N, Sumiyama K. Robotic Platforms for Therapeutic Flexible Endoscopy: A Literature Review. Diagnostics (Basel) 2024;14:595. [Crossref] [PubMed]
24. Tham CE, Rea D, Tham TC. Artificial Intelligence in Endoscopy: A Narrative Review. Ulster Med J 2025;94:16-23. [PubMed]
25. Cai SL, Li B, Tan WM, et al. Using a deep learning system in endoscopy for screening of early esophageal squamous cell carcinoma (with video). Gastrointest Endosc 2019;90:745-53.e2. [Crossref] [PubMed]
26. Luo H, Xu G, Li C, et al. Real-time artificial intelligence for detection of upper gastrointestinal cancer by endoscopy: a multicentre, case-control, diagnostic study. Lancet Oncol 2019;20:1645-54. [Crossref] [PubMed]