Clinical trial NCT04593407: Endoscopic Mucosal Resection Versus Endoscopic Submucosal Dissection for Colorectal Laterally Spreading Lesions.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Neoplasms, Colorectal
Keywords: Colonic Polyps
large laterally spreading lesion
colonic adenoma
Endoscopic submucosal dissection
Endoscopic Mucosal Resection
Adenoma
Polyps
Pathological Conditions, Anatomical
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Polyps
Lead sponsor: Hospital Universitario 12 de Octubre
Sponsor class: OTHER
Collaborators: name: Spanish Society of Digestive Endoscopy
First posted: 2020-10-20
Enrollment: 376
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of surgical referral after treatment
timeFrame: Month 18
Secondary outcomes:
measure: En bloc resection rate
timeFrame: Month 1
measure: R0 resection rate
timeFrame: Month 1
measure: Duration of the procedure
timeFrame: Month 1
measure: Percentage of curative resection rates without surgery
timeFrame: Month 18
measure: Proportion of cases in which the endoscopist has to change technique to the alternative procedure
timeFrame: Month 1
measure: Cumulative complications rate after treatment
timeFrame: Month 1 and 18
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital Universitario "12 de Octubre"
Study officials:
affiliation: Hospital Universitario 12 de Octubre
name: José C. Marín-Gabriel, Assoc. Prof.
role: STUDY_DIRECTOR
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