Comparison of Endoscopic Resection and Surgery for Early Gastric Cancer With Undifferentiated Histological Type

Study Overview
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Brief Summary
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This multi-center, randomized controlled trial is designed to evaluate clinical effectiveness and cost-effectiveness of ESD for undifferentiated type of EGC meeting the expanded indication compared with surgery.

Detailed Description
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Endoscopic submucosal dissection (ESD) is a minimally invasive treatment of early gastric cancer (EGC). Because of the stomach preservation, ESD provides a better quality of life (QoL) in EGC patients than surgery. In addition, medical costs are lower in patients underwent ESD than in those underwent surgery. In 2018, gastric cancer management guidelines by the Korean Gastric Cancer Association and Japanese Gastric Cancer Association (JGCA) stated that undifferentiated type of EGC, clinically diagnosed as tumor confined to the mucosa without ulcer, and size ≤2 cm, is included in the expanded indication of ESD. In the 2018 JGCA guideline (version 5), ESD is an investigational treatment for patients with undifferentiated type of EGC meeting the expanded indication whereas surgery (gastrectomy with lymph node dissection) is a standard treatment. Previous single center retrospective studies reported favorable long-term outcomes of ESD for undifferentiated type EGC meeting the expanded criteria on final pathological evaluations compared with that of surgery. More recently, a multi-center retrospective cohort study including 18 Korean university hospitals also reported no significant difference in overall mortality between ESD and surgery after propensity score matching (hazard ratio [HR] for overall mortality in the ESD group, 2.36; 95% confidence interval [CI] 0.91-6.10; p=0.078) during a median follow-up of 75.6 months. However, gastric cancer recurrence occurred only in the ESD group, and the HR for gastric cancer recurrence in the ESD group was 25.49 (95% CI 1.32-491.27; p=0.032). The 3-year disease-free survival (DFS) rate including gastric cancer recurrence or death was 94.9% in the ESD group and 98.1% in the surgery group. Thus, surgery group had a better DFS than ESD group (p=0.002 by log-rank test), and the HR for gastric cancer recurrence or death in the surgery group compared with the ESD group was 0.26 (95% CI, 0.10-0.64; p=0.003). However, previous studies could provide only a low level of evidence because of study limitations including the retrospective study design and incomplete data of patient survival and gastric cancer recurrence during follow-up. The studies did not evaluate QoL and cost-effectiveness after ESD and surgery. Therefore, we designed a multi-center, randomized controlled trial to provide a high level of evidence for clinical effectiveness and cost-effectiveness of ESD for undifferentiated type of EGC meeting the expanded indication.

Official Title
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Comparison of Endoscopic Resection and Surgery for Early Gastric Cancer With Undifferentiated Histological Type: a Multicenter Randomized Controlled Trial (ERASE-GC Trial)

Conditions
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Stomach Cancer, Undifferentiated Type, Expanded Indication of Endoscopic Resection

Intervention / Treatment
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* Procedure: Endoscopic submucosal dissection
* Procedure: Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who are diagnosed with undifferentiated type EGC (signet ring cell carcinoma, poorly differentiated tubular adenocarcinoma, or poorly cohesive carcinoma) that meets the expanded indication of ESD 1) Tumor confined to the mucosa without ulcer, and size ≤2 cm on endoscopic evaluations 2) No evidence of lymph node metastasis and distant metastasis on abdominal CT scan Adult patients aged 19-75 years Patients who had willingness to sign an informed consent form Exclusion Criteria: Patient age: < 19 years or age > 75 years Diagnosis and active treatment for other organ cancer except carcinoma in situ and non-melanomatous skin cancer within 5 years Previous gastrectomy or esophagectomy history Multiple gastric cancers Current treatment for serious medical condition which could hinder study participation including severe heart dysfunction, liver cirrhosis, renal failure, chronic obstructive pulmonary disease or asthma, or uncontrolled infection Inability to provide an informed consent Inadequate conditions for study enrollment according to the evaluation of study physicians

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Endoscopic treatment arm<br>Endoscopic submucosal dissection | Procedure: Endoscopic submucosal dissection<br>* Endoscopic submucosal dissection by a endoscopist using endoscopic devices<br>|
| Active Comparator: Surgical treatment group<br>Gastrectomy with lymph node dissection | Procedure: Surgery<br>* Gastrectomy with lymph node dissection by a surgeon<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year disease-free survival in the ITT population | Disease-free survival (gastric cancer recurrence or death from any causes) | 3 years after the last participant enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year disease-free survival in the PP population | Disease-free survival (gastric cancer recurrence or death from any causes) | 3 years after the last participant enrollment | 
| Overall survival | Overall survival (death from any causes) | 5 years after the last participant enrollment | 
| Curative resection rate of ESD | Curative resection on the final pathological evaluation | 2 year after the participant enrollment | 
| Quality of life changes during follow-up periods | QoL changes using questionnaire | 3 years after the last participant enrollment | 
| Treatment related complications (adverse events) | Early (within 30 postoperative days) and late complications (after 30 postoperative days) | 3 years after the last participant enrollment | 
| Cost-effectiveness measured with Incremental cost effective ratio (ICER) |  | 3 years after the last participant enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Early gastric cancer, Endoscopic submucosal dissection, Surgery, Undifferentiated type, Expanded indication