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

Neoplasms, Colorectal Clinical Trial

— intERsection  

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04593407
• Other study ID #: intERsection-19/281
• Status: Recruiting
• Phase: N/A
• Start date: November 3, 2020
• Est. completion date: September 30, 2024

Study information

• Verified date: September 2023
• Source: Hospital Universitario 12 de Octubre
• Contact: José C. Marín-Gabriel, Assoc. Prof.
• Phone: +34 91 779 28 27
• Email: josecarlos.marin[@]salud.madrid.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 376
• Est. completion date: September 30, 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Neoplasms
• Neoplasms, Colorectal

Intervention

Procedure:
• Endoscopic mucosal resection (EMR)
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
• Endoscopic submucosal dissection (ESD)
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.

Locations

Country	Name	City	State
Spain	Hospital Universitario "12 de Octubre"	Madrid

Sponsors (2)

Lead Sponsor	Collaborator
José Carlos Marín Gabriel	Spanish Society of Digestive Endoscopy

Country where clinical trial is conducted

Spain, 

References & Publications (26)

Albeniz E, Pellise M, Gimeno-Garcia AZ, Lucendo AJ, Alonso-Aguirre PA, Herreros de Tejada A, Alvarez MA, Fraile M, Herraiz Bayod M, Lopez Roses L, Martinez Ares D, Ono A, Parra Blanco A, Redondo E, Sanchez-Yague A, Soto S, Diaz-Tasende J, Montes Diaz M, Rodriguez-Tellez M, Garcia O, Zuniga Ripa A, Hernandez Conde M, Alberca de Las Parras F, Gargallo CJ, Saperas E, Munoz Navas M, Gordillo J, Ramos Zabala F, Echevarria JM, Bustamante M, Gonzalez-Haba M, Gonzalez-Huix F, Gonzalez-Suarez B, Vila Costas JJ, Guarner Argente C, Mugica F, Cobian J, Rodriguez Sanchez J, Lopez Viedma B, Pin N, Marin Gabriel JC, Nogales O, de la Pena J, Navajas Leon FJ, Leon Brito H, Remedios D, Esteban JM, Barquero D, Martinez Cara JG, Martinez Alcala F, Fernandez-Urien I, Valdivielso E. Clinical guidelines for endoscopic mucosal resection of non-pedunculated colorectal lesions. Rev Esp Enferm Dig. 2018 Mar;110(3):179-194. doi: 10.17235/reed.2018.5086/2017. — View Citation

Arezzo A, Passera R, Marchese N, Galloro G, Manta R, Cirocchi R. Systematic review and meta-analysis of endoscopic submucosal dissection vs endoscopic mucosal resection for colorectal lesions. United European Gastroenterol J. 2016 Feb;4(1):18-29. doi: 10.1177/2050640615585470. Epub 2015 May 5. — View Citation

Bahin FF, Heitman SJ, Rasouli KN, Mahajan H, McLeod D, Lee EYT, Williams SJ, Bourke MJ. Wide-field endoscopic mucosal resection versus endoscopic submucosal dissection for laterally spreading colorectal lesions: a cost-effectiveness analysis. Gut. 2018 Nov;67(11):1965-1973. doi: 10.1136/gutjnl-2017-313823. Epub 2017 Oct 7. — View Citation

Belderbos TD, Leenders M, Moons LM, Siersema PD. Local recurrence after endoscopic mucosal resection of nonpedunculated colorectal lesions: systematic review and meta-analysis. Endoscopy. 2014 May;46(5):388-402. doi: 10.1055/s-0034-1364970. Epub 2014 Mar 26. — View Citation

Bogie RMM, Veldman MHJ, Snijders LARS, Winkens B, Kaltenbach T, Masclee AAM, Matsuda T, Rondagh EJA, Soetikno R, Tanaka S, Chiu HM, Sanduleanu-Dascalescu S. Endoscopic subtypes of colorectal laterally spreading tumors (LSTs) and the risk of submucosal invasion: a meta-analysis. Endoscopy. 2018 Mar;50(3):263-282. doi: 10.1055/s-0043-121144. Epub 2017 Nov 27. Erratum In: Endoscopy. 2018 Mar;50(3):C4. — View Citation

Bourke MJ, Neuhaus H, Bergman JJ. Endoscopic Submucosal Dissection: Indications and Application in Western Endoscopy Practice. Gastroenterology. 2018 May;154(7):1887-1900.e5. doi: 10.1053/j.gastro.2018.01.068. Epub 2018 Mar 2. — View Citation

Burgess NG, Hourigan LF, Zanati SA, Brown GJ, Singh R, Williams SJ, Raftopoulos SC, Ormonde D, Moss A, Byth K, Mahajan H, McLeod D, Bourke MJ. Risk Stratification for Covert Invasive Cancer Among Patients Referred for Colonic Endoscopic Mucosal Resection: A Large Multicenter Cohort. Gastroenterology. 2017 Sep;153(3):732-742.e1. doi: 10.1053/j.gastro.2017.05.047. Epub 2017 Jun 2. — View Citation

Emmanuel A, Gulati S, Burt M, Hayee B, Haji A. Colorectal endoscopic submucosal dissection: patient selection and special considerations. Clin Exp Gastroenterol. 2017 Jul 13;10:121-131. doi: 10.2147/CEG.S120395. eCollection 2017. — View Citation

Ferlitsch M, Moss A, Hassan C, Bhandari P, Dumonceau JM, Paspatis G, Jover R, Langner C, Bronzwaer M, Nalankilli K, Fockens P, Hazzan R, Gralnek IM, Gschwantler M, Waldmann E, Jeschek P, Penz D, Heresbach D, Moons L, Lemmers A, Paraskeva K, Pohl J, Ponchon T, Regula J, Repici A, Rutter MD, Burgess NG, Bourke MJ. Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy. 2017 Mar;49(3):270-297. doi: 10.1055/s-0043-102569. Epub 2017 Feb 17. — View Citation

Fujiya M, Tanaka K, Dokoshi T, Tominaga M, Ueno N, Inaba Y, Ito T, Moriichi K, Kohgo Y. Efficacy and adverse events of EMR and endoscopic submucosal dissection for the treatment of colon neoplasms: a meta-analysis of studies comparing EMR and endoscopic submucosal dissection. Gastrointest Endosc. 2015 Mar;81(3):583-95. doi: 10.1016/j.gie.2014.07.034. Epub 2015 Jan 13. — View Citation

Gupta S, Miskovic D, Bhandari P, Dolwani S, McKaig B, Pullan R, Rembacken B, Riley S, Rutter MD, Suzuki N, Tsiamoulos Z, Valori R, Vance ME, Faiz OD, Saunders BP, Thomas-Gibson S. A novel method for determining the difficulty of colonoscopic polypectomy. Frontline Gastroenterol. 2013 Oct;4(4):244-248. doi: 10.1136/flgastro-2013-100331. Epub 2013 Jun 1. — View Citation

Klein A, Tate DJ, Jayasekeran V, Hourigan L, Singh R, Brown G, Bahin FF, Burgess N, Williams SJ, Lee E, Sidhu M, Byth K, Bourke MJ. Thermal Ablation of Mucosal Defect Margins Reduces Adenoma Recurrence After Colonic Endoscopic Mucosal Resection. Gastroenterology. 2019 Feb;156(3):604-613.e3. doi: 10.1053/j.gastro.2018.10.003. Epub 2018 Oct 6. — View Citation

Moss A, Bourke MJ, Williams SJ, Hourigan LF, Brown G, Tam W, Singh R, Zanati S, Chen RY, Byth K. Endoscopic mucosal resection outcomes and prediction of submucosal cancer from advanced colonic mucosal neoplasia. Gastroenterology. 2011 Jun;140(7):1909-18. doi: 10.1053/j.gastro.2011.02.062. Epub 2011 Mar 8. — View Citation

Moss A, Williams SJ, Hourigan LF, Brown G, Tam W, Singh R, Zanati S, Burgess NG, Sonson R, Byth K, Bourke MJ. Long-term adenoma recurrence following wide-field endoscopic mucosal resection (WF-EMR) for advanced colonic mucosal neoplasia is infrequent: results and risk factors in 1000 cases from the Australian Colonic EMR (ACE) study. Gut. 2015 Jan;64(1):57-65. doi: 10.1136/gutjnl-2013-305516. Epub 2014 Jul 1. — View Citation

Oka S, Tanaka S, Kanao H, Oba S, Chayama K. Therapeutic strategy for colorectal laterally spreading tumor. Dig Endosc. 2009 Jul;21 Suppl 1:S43-6. doi: 10.1111/j.1443-1661.2009.00869.x. — View Citation

Oyama T, Yahagi N, Ponchon T, Kiesslich T, Berr F. How to establish endoscopic submucosal dissection in Western countries. World J Gastroenterol. 2015 Oct 28;21(40):11209-20. doi: 10.3748/wjg.v21.i40.11209. — View Citation

Repici A, Hassan C, De Paula Pessoa D, Pagano N, Arezzo A, Zullo A, Lorenzetti R, Marmo R. Efficacy and safety of endoscopic submucosal dissection for colorectal neoplasia: a systematic review. Endoscopy. 2012 Feb;44(2):137-50. doi: 10.1055/s-0031-1291448. Epub 2012 Jan 23. — View Citation

Russo P, Barbeiro S, Awadie H, Libanio D, Dinis-Ribeiro M, Bourke M. Management of colorectal laterally spreading tumors: a systematic review and meta-analysis. Endosc Int Open. 2019 Feb;7(2):E239-E259. doi: 10.1055/a-0732-487. Epub 2019 Jan 30. — View Citation

Saito Y, Uraoka T, Yamaguchi Y, Hotta K, Sakamoto N, Ikematsu H, Fukuzawa M, Kobayashi N, Nasu J, Michida T, Yoshida S, Ikehara H, Otake Y, Nakajima T, Matsuda T, Saito D. A prospective, multicenter study of 1111 colorectal endoscopic submucosal dissections (with video). Gastrointest Endosc. 2010 Dec;72(6):1217-25. doi: 10.1016/j.gie.2010.08.004. Epub 2010 Oct 27. — View Citation

Tate DJ, Awadie H, Bahin FF, Desomer L, Lee R, Heitman SJ, Goodrick K, Bourke MJ. Wide-field piecemeal cold snare polypectomy of large sessile serrated polyps without a submucosal injection is safe. Endoscopy. 2018 Mar;50(3):248-252. doi: 10.1055/s-0043-121219. Epub 2017 Nov 23. — View Citation

Thoguluva Chandrasekar V, Spadaccini M, Aziz M, Maselli R, Hassan S, Fuccio L, Duvvuri A, Frazzoni L, Desai M, Fugazza A, Jegadeesan R, Colombo M, Dasari CS, Hassan C, Sharma P, Repici A. Cold snare endoscopic resection of nonpedunculated colorectal polyps larger than 10 mm: a systematic review and pooled-analysis. Gastrointest Endosc. 2019 May;89(5):929-936.e3. doi: 10.1016/j.gie.2018.12.022. Epub 2019 Jan 9. — View Citation

Uraoka T, Parra-Blanco A, Yahagi N. Colorectal endoscopic submucosal dissection in Japan and Western countries. Dig Endosc. 2012 May;24 Suppl 1:80-3. doi: 10.1111/j.1443-1661.2012.01279.x. — View Citation

Uraoka T, Saito Y, Matsuda T, Ikehara H, Gotoda T, Saito D, Fujii T. Endoscopic indications for endoscopic mucosal resection of laterally spreading tumours in the colorectum. Gut. 2006 Nov;55(11):1592-7. doi: 10.1136/gut.2005.087452. Epub 2006 May 8. — View Citation

Wang J, Zhang XH, Ge J, Yang CM, Liu JY, Zhao SL. Endoscopic submucosal dissection vs endoscopic mucosal resection for colorectal tumors: a meta-analysis. World J Gastroenterol. 2014 Jul 7;20(25):8282-7. doi: 10.3748/wjg.v20.i25.8282. — View Citation

Yamada M, Saito Y, Sakamoto T, Nakajima T, Kushima R, Parra-Blanco A, Matsuda T. Endoscopic predictors of deep submucosal invasion in colorectal laterally spreading tumors. Endoscopy. 2016 May;48(5):456-64. doi: 10.1055/s-0042-100453. Epub 2016 Feb 26. — View Citation

Yang D, Othman M, Draganov PV. Endoscopic Mucosal Resection vs Endoscopic Submucosal Dissection For Barrett's Esophagus and Colorectal Neoplasia. Clin Gastroenterol Hepatol. 2019 May;17(6):1019-1028. doi: 10.1016/j.cgh.2018.09.030. Epub 2018 Sep 26. — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of surgical referral after treatment	Compare between two groups.	Month 18
Secondary	En bloc resection rate	Compare between two groups	Month 1
Secondary	R0 resection rate	Compare between two groups	Month 1
Secondary	Duration of the procedure	Compare between two groups	Month 1
Secondary	Percentage of curative resection rates without surgery	Compare between two groups	Month 18
Secondary	Proportion of cases in which the endoscopist has to change technique to the alternative procedure	Compare between two groups	Month 1
Secondary	Cumulative complications rate after treatment	Compare between two groups	Month 1 and 18