RCT of EFTR Versus STER for GIST Treatment

February 9, 2026 updated by: Hon Chi Yip, Chinese University of Hong Kong

Exposed Endoscopic Full Thickness Resection (EFTR) Versus Submucosal Tunnelling Endoscopic Resection (STER) for Small Gastric Gastrointestinal Stromal Tumor (GIST) - an International Double Blinded Randomized Controlled Trial

Endoscopic resection has been increasing utilized as the treatment for small size gastrointestinal stromal tumors (GIST), of which the best resection method has not been identified. We aim to compare the outcomes of endoscopic full thickness resection (EFTR) versus submucosal tunnelling endoscopic resection (STER) for clinical small gastric GIST. We hypothesize that EFTR could achieve better complete margin negative resection than STER without increase in adverse event.

This is an international multi-center double blinded randomized controlled trial involving four high volume centers from Hong Kong, mainland China, India and Japan. Adult patients with clinical 1.0-3.Scm gastric GIST undergoing endoscopic resection would be recruited.

Patients would be randomized to undergo EFTR (intervention) or STER (Control) by expert endoscopists under general anaesthesia according to well published methods.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumors in the GI tract, often located in the stomach. Based on the latest World Health Organization (WHO) classification, all GISTs are now considered as malignant tumors. Large size overtly aggressive GISTs are relatively rare, occurring only in up to 8 per million population. However, smaller sizes GIST in the stomach are relatively common, and was found in up to 20% of patients based on autopsy series.

Conventionally, localized GISTs are treated by surgical resection. Several guidelines recommended resection of all histologically confirmed GIST, while some suggested surveillance if the lesion is small <2cm in size. The principle of surgery for GIST is for en-bloc margin negative complete resection, while lymph node dissection is not required. As such, laparoscopic resection of gastric GIST has been advocated when technically feasible, demonstrating short term benefits in recovery than open surgery, with similar oncological outcomes.

With the technological advances of endoscopic surgery including endoscopic submucosal dissection (ESD) for early epithelial cancers and per-oral endoscopic myotomy (POEM), there was a rapid expansion in the indication of endoscopic surgery, in particular resection of subepithelial tumors (SET) in the gastrointestinal tract, in which a significant proportion are GISTs. Systematic review revealed a shorter procedure time and improved short-term recovery by endoscopic resection versus laparoscopic resection, without significant difference in complication and survival. With the favourable outcomes consistently reported in the literature regarding endoscopic resection of upper gastrointestinal GISTs, several endoscopy and oncology society guidelines are now recommending endoscopic resection as an option for smaller size GISTs in institutions with expertise on therapeutic endoscopy.

Submucosal tunneling endoscopic resection (STER) was first reported by Xu, et al in 2012. The concept of the procedure is to create a submucosal tunnel away from the tumor that arose from the musclaris propria layer while protecting the mucosa directly overlying the lesion, so that only mucosal closure of the tunnel entrance would be required after resection. The technique was first used on esophageal SET, where majority of them are benign leiomyoma. STER was then subsequently applied to other upper gastrointestinal tract lesions including the stomach. The merit of the technique mainly lies in the simplicity of closure of the mucosal incision, which only requires simple through-the-scope (TTS) clips. A schematic diagram of the STER procedure is shown in Figure 1.

Development of various techniques that allowed secure endoscopic water-tight closure of full thickness wall defect has led to increasing application of endoscopic full thickness resection (EFTR). As opposed to the STER procedure, the tumor would be directly resected without creation of a submucosal tunnel. This would create a full thickness defect that required complete closure to avoid gastrointestinal leakage and peritonitis. Various methods have been reported for closure, ranging from simple TTS clip closure, over-the-scope clip closure, clip endo-loop purse string technique, re-openable clip over-the-line method (ROLM), endoscopic suturing etc. With appropriate selection of closure method based on the morphology of the defect, secure closure could be achieved with minimal post-procedural morbidity.

American Society of Gastrointestinal Endoscopy (ASGE) has recently published a guideline on endoscopic full thickness resection, where STER procedure would be classified as exposed tunneled type EFTR. The EFTR procedure mentioned in previous paragraph would be classified as exposed non-tunneled type EFTR. Due to the complexity of the nomenclature, EFTR and STER will be used in the subsequent text for easier understanding of the technique described.

Both EFTR and STER has been increasingly utilized in resecting gastric subepithelial tumors including GISTs. In a recent systematic review of 952 gastric EFTR procedures including 523 GISTs, en-bloc margin negative resection was achieved in 99.3%, with surgical conversion rate of 0.09%. Pooled estimate of major adverse event was only 0.29%. On the other hand, systematic review of 2941 STER procedure reported margin negative resection rate of 92.4% with major adverse event of 1.2%. Of note, when only gastric lesion or lesion arising from muscularis propria layer were considered, the margin negative resection rate dropped to 90.6% and 88.3% respectively. While both procedures remained safe and feasible, margin negative resection appeared to be better achieved with EFTR. In the aforementioned studies, recurrence was observed on 0% and 2.3% of patients after EFTR and STER respectively.

The investigators have recently reported a retrospective analysis comparing EFTR and STER for gastric GISTs. In line with the current literature, complete margin negative resection was achieved in a significantly higher proportion with EFTR than STER (100% versus 80%, p=0.029), while no difference was found in the incidence of post-procedural adverse event. It is believed that EFTR is superior to STER in obtaining clear surgical margin, as dissection within the submucosal tunnel is challenging in achieving a wide margin without breaching tumor capsule, especially when tumor size is larger than 2cm. The concern for inadequate defect closure has also recently been overcome by numerous new developments of full thickness closure methods as described above. In the study, local recurrence was observed in 1 patient after STER, while no recurrence was found in the EFTR group. The event rate of recurrence was both low for both STER and EFTR, thus statistically significant difference could not be detected without a huge sample size. Nonetheless, it is however anticipated that with better margin negative resection, EFTR could achieve a lower recurrence rate for malignant GIST than STER, and margin negative complete resection should be a reasonable surrogate outcome for oncological clearance.

To date there has not been any prospective comparative study comparing EFTR and STER for small size gastric GISTs. The investigators have therefore designed the current international prospective randomized controlled trial aiming to demonstrate the superiority of EFTR in achieving better margin negative resection.

Study Type

Interventional

Enrollment (Estimated)

136

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Shanghai, China
        • Not yet recruiting
        • Department of Gastroenterology, Zhongshan Hospital of Fudan University
  • Hong Kong
      • Hong Kong, Hong Kong
        • Recruiting
        • Department of Surgery, Faculty of Medicine, the Chinese University of Hong Kong
        • Contact:
  • India
      • Hyderabad, India
  • Japan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Consecutive adult patients age >=18 and <=75 with a clinical diagnosis of gastric GIST who opted for endoscopic resection would be screened for eligibility.

Inclusion Criteria:

  • Presence of gastric subepithelial tumor on diagnostic upper endoscopy, and
  • Diagnostic EUS and CT scan with intravenous contrast suspicious of GIST arising from muscularis propria layer, size with maximum diameter >=1.0cm and <= 3.5cm, and
  • Absence of high risk features, including irregular margins, invasion to surrounding organs, lesion hypervascularity, and
  • Endoscopic morphology and location deemed feasible with both EFTR and STER by an expert endoscopist, or
  • Histological confirmation of GIST through EUS guided fine needle biopsy (Optional, based on recommendation from guidelines)

Exclusion Criteria:

  • Patients with tumors deemed not suitable for endoscopic resection (Either EFTR or STER), due to unfavourable location, high risk morphology, or any other reasons.
  • Patients with multiple tumors.
  • Patients unable or unwilling to provide consent.
  • Previous esophageal or gastric surgery.
  • Patients with significant cardiorespiratory comorbidities which may limit their ability to undertake general anesthesia for the procedure, including ASA grade III or above.
  • Pregnant women or those planning pregnancy or breastfeeding women.
  • Uncorrectable coagulopathy defined by international normalized ratio (INR) > 1.5 or platelet count < 50000/µl.
  • Patients on double anti-platelet agents or anti-coagulation (Warfarin, heparin or other direct oral anticoagulants)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Endoscopic full thickness resection (EFTR) Group
Patients would be randomized to undergo EFTR by expert endoscopists under general anaesthesia according to well published methods.
Procedure: Endoscopic full thickness resection (EFTR) / Exposed non-tunneling EFTR
The procedure would be performed in similar way as reported in the literature. A therapeutic endoscope would be used and the target lesion identified. After submucosal injection of solution around the lesion, mucosal incision would be performed with dedicated dissection knife, followed by submucosal dissection. After adequate submucosal dissection to expose the muscularis propria layer around the tumor, the muscle layer would be dissected to achieve full thickness resection. Care would be taken to avoid breaching of the tumor capsule during the procedure and to aim for en-bloc tumor resection. During the procedure, countertraction technique could be utilized according to the discretion of the endoscopists. Clip or snare related traction methods such as clip-line traction are allowed depending on the endoscopists' preference. In case of development of significant pneumoperitoneum, decompression could be performed by transcutaneous needle.
Active Comparator: Submucosal Tunneling Endoscopic Resection (STER) Group
Patients would be randomized to undergo STER by expert endoscopists under general anaesthesia according to well published methods.
Procedure: Submucosal Tunneling Endoscopic Resection (STER) / Exposed tunneling EFTR
As with exposed EFTR, the STER procedure would also be performed in similar way as reported in literature. After identification of the tumor location, a mucosal incision would be made at 3-4cm proximal to it after submucosal injection of saline mixture. Submucosal tunnel would then be created until identification of the tumor within the tunnel. Circumferential dissection would then be performed around the tumor until complete resection is achieved. During the procedure, the dissection plane would aim to avoid breaching tumor capsule in similar manner with EFTR group. The resected specimen would then be retrieved through the tunnel opening. After confirming adequate haemostasis within the submucosal tunnel, the mucosal incision would be closed with TTS clips. In case of failure of STER, cross-over to EFTR would be allowed in order to achieve tumor resection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete R0 resection
Time Frame: 1 day

Complete R0 resection, defined as en-bloc complete endoscopic resection with intact tumor capsule and histological negative resection margins.

Measure unit: % of lesions.
1 day

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of Intra-procedural adverse events
Time Frame: 1 day

Intra-procedural adverse events (AE), including specific AE such as haemorrhage, tension capnoperitoneum, injury to adjacent peritoneal organs, unintentional mucosal injury / perforation, failed tumor retrieval, and general AE such as cardiovascular, pulmonary or other anaesthetic related events. All adverse events would be documented and graded based on the Common Terminology Criteria for Adverse Event (CTCAE) version 5.0 and ASGE endoscopic adverse event Lexicon.

Measure unit: % of procedure.
1 day
Rate of post-procedural adverse events
Time Frame: 30 days

Post-procedural adverse events within 30 days, including specific AE such as delayed haemorrhage, peritonitis, intra-abdominal abscess / collection, and general AE such as cardiovascular, pulmonary or other anaesthetic related events. All adverse events would be documented and graded based on the Common Terminology Criteria for Adverse Event (CTCAE) version 5.0 and ASGE endoscopic adverse event Lexicon.

Measure unit: % of procedure.
30 days
Procedure time
Time Frame: 1 day

Defined from beginning of mucosal incision until complete closure of the defect (full thickness defect or tunnel opening) after tumor resection.

Measure unit: Minutes.
1 day
Crossover rate to EFTR in STER group
Time Frame: 30 days

Crossover rate to EFTR due to failure in STER group., defined as proportion of STER-assigned cases requiring crossover to EFTR (%).

Measure unit: % of patients.
30 days
Conversion rate to major surgery
Time Frame: 30 days

Rate of conversion to major surgery as salvage for failure or adverse event, defined as proportion of cases requiring conversion to major surgery (%).

Measure unit: % of patients.
30 days
Recurrence rate
Time Frame: 30 days

Recurrence rate on surveillance endoscopy and Computed Tomography. defined as proportion of patients with local or distant tumor recurrence (%).

Measure unit: % of patients.
30 days
Patient-reported VAS scores
Time Frame: Day 1, 3, 7, and 14 after procedure

Patient reported outcomes on post-procedural pain at Day 1, 3, 7, 14 after procedure, using Visual Analogue Scale (VAS) (range: 1-10), where higher score means higher level of pain.

Measure unit: VAS score (0-10)
Day 1, 3, 7, and 14 after procedure
Endoscopist-rated procedural difficulty
Time Frame: 1 day

Endoscopist rating of procedural difficulty, according to Likert scale of 1-5, where higher score indicates more perceived difficulty.

Measure unit: Likert score 1-5
1 day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chinese University of Hong Kong

Collaborators

Fudan University
Asian Institute of Gastroenterology, India
Osaka International Cancer Institute

Investigators

  • Principal Investigator: Hon Chi Yip, Chinese University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2025

Primary Completion (Estimated)

December 1, 2032

Study Completion (Estimated)

February 1, 2033

Study Registration Dates

First Submitted

February 9, 2026

First Submitted That Met QC Criteria

February 9, 2026

First Posted (Actual)

February 13, 2026

Study Record Updates

Last Update Posted (Actual)

February 13, 2026

Last Update Submitted That Met QC Criteria

February 9, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRE-2024.509

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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