Endoscopic Mucosal Resection Versus Endoscopic Submucosal Dissection for Colorectal Laterally Spreading Lesions.

Study Overview
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Brief Summary
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EMR and ESD are both effective and safe and are associated with a very low risk of procedure related mortality when performed for colorectal laterally spreading lesions (LSL). Some kind of LSLs have a low risk of submucosal invasive carcinoma (SMIC) or these foci are found in well demarcated areas of the tumor. This is the case of the non-granular flat elevated (LSN-NG-FE) and the LSLs-G mixed subtypes. The investigators aim to assess if piecemeal EMR (the older technique) for LSLs-G mixed type > 30 mm and LSLs-NG FE type > 20 mm is not inferior to ESD (the new treatment) for the need of additional surgery in the mid-term.

Detailed Description
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Endoscopic submucosal dissection (ESD) is curative for lesions with superficial submucosal invasive carcinoma (s-SMIC) and favourable histological features. The procedure is performed mainly for laterally spreading lesions (LSLs) and is the reference treatment for these neoplasms in Asian countries nowadays. LSLs can be granular (G) or non-granular (NG). Most LSLs-G homogenous type are superficial and can be resected by EMR because SMIC is often lacking. On the other hand, since LSLs-G mixed type > 20 - 30 mm have a higher prevalence of SMIC when compared with the homogenous subtype, Asian experts now recommend ESD for this kind of tumors. However, some years ago, EMR had been suggested for LSLs-G mixed type if the largest nodule was resected first and the histological assessment was done separately. The rationale for the latter approach is that the invasive component is usually found within the large nodule. Conversely, the prevalence of SMIC is higher in LSLs-NG PD type, therefore, ESD is the preferred therapeutic intervention. In addition, LSLs-NG FE type have been associated with multifocal invasion in Japanese studies. However, in Western countries, the percentage of SMIC in LSLs-NG FE type > 20 mm seems much lower than previously described in Asian series. Thus, the investigators do not know if EMR might be enough to remove these tumours. Furthermore, if the risk of s-SMIC is low, the recurrence rates for ESD in these kind of lesions (LSL-G mixed type > 30 mm and LSL-NG FE type > 20 mm) might be comparable to that of piecemeal EMR, in terms of curative resection (avoiding the need for surgery) in the mid-term. When performing an EMR, recurrences are more frequent, but they are largely inconsequential because it is usually unifocal, diminutive and easily can be managed endoscopically on subsequent sessions. In order to clarify the controversial issue of performing colorectal ESD in Western countries, the investigators aim to assess if piecemeal EMR (the older technique) for LSLs-G mixed type > 30 mm and LSLs-NG FE type > 20 mm is not inferior to ESD (the new treatment) for the need of additional surgery in the mid-term.

Official Title
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Endoscopic Mucosal Resection Versus Endoscopic Submucosal Dissection for Laterally Spreading Lesions Non Granular-Flat Elevated Type (LSL-NG-FE) ≥ 20 mm and LSLs-Granular Mixed Type ≥ 30 mm. A Randomized, Non-inferiority Trial.

Conditions
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Neoplasms, Colorectal

Intervention / Treatment
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* Procedure: Endoscopic mucosal resection (EMR)
* Procedure: Endoscopic submucosal dissection (ESD)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults (at least 18 years old). LSL-NG FE type ≥ 20mm or LST-G mixed type ≥30mm who have not been previously treated or received submucosal injection, regardless of their location in the colon. LSL-NG FE type ≥ 20mm or LST-G mixed type ≥30mm WITHOUT a demarcated area The patient must have undergone a complete colonoscopy, reaching the cecum, to detect possible synchronous lesion. If this procedure has not been done previously, it will be performed prior to the inclusion of the patient in the study. Patients able to fill in questionnaires written in Spanish or English. Exclusion Criteria: Contra-indication to colonoscopy. Contra-indication to general anesthesia. Inability to stop antiplatelet agents and anti-coagulant according to the European Society of Gastro-Intestinal Endoscopy guidelines. Patients with > 1 lesion meeting the inclusion criteria. LSL-NG FE type ≥ 20mm or LST-G ≥30mm mixed type that have been previously treated (Recurrence or residual lesion after previous endoscopic or surgical treatment). LSL-NG FE type ≥ 20mm or LST-G ≥30mm mixed type with previous submucosal injection, even if a resection attempt with a snare was not finally performed. Lesions with suspicion of deep submucosal invasive carcinoma: depression or invasive pit-pattern (Vi within a demarcated area or Vn). Submucosal mass like elevation within a LSL-NG FE type. LSLs having a previous biopsy or tattooing. Previous biopsies of the lesion should only be allowed if LSL-G mixed type > 30 mm and samples were taken out of the flat area. LSL-G with a Buddha like deformation (Polyp on polyp) LSL involving a surgical anastomosis. LSL involving the appendicular orifice. LSL involving the terminal ileum. Patient's refusal to participate in the study Presence of inflammatory bowel disease Pregnant or lactating women. Hereditary colorectal cancer syndrome or hereditary polyposis. Patient under legal protection and or deprived of liberty by judicial or administrative decision. Patient already participating in an interventional clinical research protocol Patient who cannot be followed for the duration of the study. Inability to sign the informed consent of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Endoscopic Mucosal Resection (EMR):<br>Piecemeal EMR is a conventional endoscopic resection technique. A submucosal injection of a large volume of a solution (normal saline or other) with or without dilute epinephrine (1/10,000) with or without indigo carmine is performed. Then, sequential piecemeal resection is performed with use of a combination of stiff-type snares. At the end of the procedure when macroscopically visible adenoma has been totally resected, a snare tip soft coagulation (STSC) of the margin of the scar is performed to eliminate non visible residual neoplastic tissue. This procedure is quicker and safer than ESD but led to more recurrent disease (around 20% with the standard technique but recently reduced to 5% after the introduction of STSC) | Procedure: Endoscopic mucosal resection (EMR)<br>* Endoscopic mucosal resection (EMR) is an endoscopic resection technique that allows the removal of large colorectal lesions using a conventional lift-and-cut procedure or an underwater technique<br>|
| Experimental: : Endoscopic Submucosal Dissection (ESD):<br>ESD is a newer resection technique that allows en bloc resection for large LSLs. A submucosal injection is also needed but, in this case, different endo-knives are used to achieve the resection instead of diathermic snares. The en bloc resection allows a more precise pathological analysis and the risk of recurrence is lower (<2%) when margins are tumor-free. | Procedure: Endoscopic submucosal dissection (ESD)<br>* Endoscopic submucosal dissection (ESD) is an endoscopic procedure that allows dissection of larger colorectal lesions in one piece using endoknives. The procedure is technically more difficult, much more time-consuming than EMR, mandates multiday hospital admission and has an increased risk of perforation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of surgical referral after treatment | Compare between two groups. | Month 18 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| En bloc resection rate | Compare between two groups | Month 1 | 
| R0 resection rate | Compare between two groups | Month 1 | 
| Duration of the procedure | Compare between two groups | Month 1 | 
| Percentage of curative resection rates without surgery | Compare between two groups | Month 18 | 
| Proportion of cases in which the endoscopist has to change technique to the alternative procedure | Compare between two groups | Month 1 | 
| Cumulative complications rate after treatment | Compare between two groups | Month 1 and 18 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoplasms by Histologic Type, Intestinal Polyps, Colonic Polyps, large laterally spreading lesion, colonic adenoma, Endoscopic submucosal dissection, Endoscopic Mucosal Resection, Adenoma, Polyps, Pathological Conditions, Anatomical, Neoplasms, Glandular and Epithelial, Neoplasms