Recurrence Rate After Endoscopic Resection of , Laterally Spreading Tumor Granular Type (LST-G) of the Colon and Rectum: Endoscopic Mucosal Resection vs. Endoscopic Submucosal Dissection (ESD vs EMR)

Recurrence Rate After Endoscopic Resection of , Laterally Spreading Tumor Granular Type (LST-G) of the Colon and Rectum: Endoscopic Mucosal Resection (EMR) vs. Endoscopic Submucosal Dissection (ESD): A Multicenter Randomized Controlled Trial ( ESD vs EMR )

Colorectal cancer is one of the leading causes of cancer-related mortality worldwide. Early-stage non-polypoid neoplastic lesions, particularly Laterally Spreading Tumors - Granular Type (LST-G) larger than 20mm, require effective endoscopic removal to prevent malignant progression. The two primary techniques for resecting these lesions are Endoscopic Mucosal Resection (EMR) and Endoscopic Submucosal Dissection (ESD).

EMR is a widely used, minimally invasive technique that involves resecting the lesion with a diathermic snare after submucosal injection. While effective and safe, EMR often necessitates piecemeal resection, increasing the risk of local recurrence. In contrast, ESD, developed in Asia, allows for en bloc resection regardless of lesion size, ensuring more accurate histopathological assessment and lower recurrence rates. However, ESD requires greater technical expertise, has longer procedural times, and carries a higher risk of complications.

In Western clinical practice, EMR remains the standard treatment, whereas ESD is selectively performed in high-expertise centers. Given the lack of randomized controlled trials comparing EMR and ESD in Western populations, this study aims to provide robust clinical evidence to guide treatment decisions.

The primary objective of this study is to compare the recurrence/residual adenomatous tissue rate at 6 and 12 months between EMR and ESD in patients with LST-G lesions of the colon and rectum

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Procedure: Endoscopic Mucosal Resection (EMR); Procedure: Endoscopic Submucosal Dissection (ESD)

• Study Type: Interventional
• Enrollment (Estimated): 282
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lucarini Matteo, MD; Phone Number: +39 0522 296423; Email: matteo.lucarini@ausl.re.it

Study Locations

• Italy
  • Bologna, Italy
    • Recruiting
    • IRCCS Azienda Ospedaliero Universitaria di Bologna - Sant'Orsola Malpighi
    • Contact: Paolo Cecinato; Email: paolo.cecinato@aosp.bo.it
    • Principal Investigator: Paolo Cecinato, MD
  • Genova, Italy
    • Recruiting
    • Ente Ospedaliero Ospedali Galliera
    • Contact: Mariachiara Campanale, MD; Email: mchiara.campanale@galliera.it
    • Principal Investigator: Mariachiara Campanale, MD
  • Milan, Italy
    • Recruiting
    • Università Vita Salute - IRCCS
    • Contact: Francesco Azzolini, MD; Email: Azzolini.Francesco@hsronline.it
    • Principal Investigator: Azzolini Francesco, MD
  • Modena, Italy
    • Recruiting
    • Ospedale Civile di Baggiovara
    • Principal Investigator: Rita Conigliaro, MD
    • Contact: Giouseppe Grande, MD; Email: giuseppegrande1984@gmail.com
  • Reggio Emilia, Italy
    • Recruiting
    • Azienda USL IRCCS Di Reggio Emilia
    • Contact: Matteo Lucarini, MD; Email: matto.lucarini@ausl.re.it
    • Principal Investigator: Romano Sassatelli, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years.
• Diagnosis of Laterally Spreading Tumor - Granular Type (LST-G) ≥ 20 mm in the colon or rectum with an indication for endoscopic resection.
• Life expectancy > 10 years.
• Ability to understand and sign the informed consent form, demonstrating comprehension of the study and willingness to participate.

Exclusion Criteria:

• Diagnosis of Laterally Spreading Tumor - Non-Granular Type (LST-NG).
• Presence of depressed areas within the lesion.
• Lesions located on a scar or anastomosis site.
• Lesions classified as Kudo Vi or Vn pattern.
• History of chronic inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease).
• Diagnosis of hereditary polyposis syndromes (e.g., familial adenomatous polyposis, Lynch syndrome).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Endoscopic Mucosal Resection (EMR)	Procedure: Endoscopic Mucosal Resection (EMR); atients assigned to this arm will undergo Endoscopic Mucosal Resection (EMR), a standard endoscopic technique that involves the resection of colorectal Laterally Spreading Tumors - Granular type (LST-G) using a diathermic snare with submucosal injection. The procedure may be performed en bloc or in a piecemeal fashion, depending on lesion size and characteristics. EMR is widely accepted for lesions with low submucosal invasion risk but has a higher recurrence rate than ESD.
Experimental: Endoscopic Submucosal Dissection (ESD)	Procedure: Endoscopic Submucosal Dissection (ESD); Patients assigned to this arm will undergo Endoscopic Submucosal Dissection (ESD), an advanced endoscopic technique that allows for en bloc resection of large colorectal Laterally Spreading Tumors - Granular type (LST-G). The procedure involves the use of specialized knives to dissect the submucosal layer, ensuring complete resection with histologically clear margins (R0 resection). ESD has been associated with lower recurrence rates but requires a high level of expertise, longer procedural times, and carries a higher risk of complications.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence/Adenomatous Residual Rate	Proportion of patients with local recurrence or residual adenomatous tissue, confirmed through follow-up colonoscopies and histopathological examination.	6 and 12 months after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Resection Rate	Proportion of patients with a complete histopathological resection (R0), defined as tumor-free margins in both lateral and deep resection edges, out of the total number of randomized patients	6 and 12 months after treatment
Differences in Procedure Time	Comparison of the average duration of the procedure (from submucosal injection to complete lesion resection) between the EMR and ESD groups. The procedure time is measured intraoperatively and is calculated as the total duration from the initial submucosal injection to the completion of lesion resection.	Up to 2 months
Bleeding Rate	Number of patients experiencing bleeding out of the total number of randomized patients.	During procedure (up to 2 months from enrollment) and 24 hours and 3 months after treatment
Perforation Rate	Number of patients with an intraoperative perforation, defined as visible mesenteric fat or free peritoneal space during the procedure, or delayed perforation diagnosed based on symptoms (abdominal pain, fever, peritonitis) and confirmed by radiological imaging (free air, fluid collection).	During procedure (up to 2 months from enrollment) and 24 hours and 3 months after treatment
Overall Complication Rate	Proportion of patients experiencing at least one complication, classified according to the Accordion Severity Classification of Postoperative Complications.	24 hours after treatment

Collaborators and Investigators

• Sponsor: Azienda USL Reggio Emilia - IRCCS
• Investigators: Principal Investigator: Sassatelli Romano, MD, Azienda USL - IRCCS di Reggio Emilia

Publications and helpful links

General Publications

• Kudo S, Hirota S, Nakajima T, Hosobe S, Kusaka H, Kobayashi T, Himori M, Yagyuu A. Colorectal tumours and pit pattern. J Clin Pathol. 1994 Oct;47(10):880-5. doi: 10.1136/jcp.47.10.880.
• Tanaka S, Kashida H, Saito Y, Yahagi N, Yamano H, Saito S, Hisabe T, Yao T, Watanabe M, Yoshida M, Kudo SE, Tsuruta O, Sugihara KI, Watanabe T, Saitoh Y, Igarashi M, Toyonaga T, Ajioka Y, Ichinose M, Matsui T, Sugita A, Sugano K, Fujimoto K, Tajiri H. JGES guidelines for colorectal endoscopic submucosal dissection/endoscopic mucosal resection. Dig Endosc. 2015 May;27(4):417-434. doi: 10.1111/den.12456. Epub 2015 Mar 5.
• 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.
• 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.
• 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.
• Strasberg SM, Linehan DC, Hawkins WG. The accordion severity grading system of surgical complications. Ann Surg. 2009 Aug;250(2):177-86. doi: 10.1097/SLA.0b013e3181afde41.
• Pimentel-Nunes P, Dinis-Ribeiro M, Ponchon T, Repici A, Vieth M, De Ceglie A, Amato A, Berr F, Bhandari P, Bialek A, Conio M, Haringsma J, Langner C, Meisner S, Messmann H, Morino M, Neuhaus H, Piessevaux H, Rugge M, Saunders BP, Robaszkiewicz M, Seewald S, Kashin S, Dumonceau JM, Hassan C, Deprez PH. Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2015 Sep;47(9):829-54. doi: 10.1055/s-0034-1392882. Epub 2015 Aug 28.
• Oka S, Tanaka S, Saito Y, Iishi H, Kudo SE, Ikematsu H, Igarashi M, Saitoh Y, Inoue Y, Kobayashi K, Hisabe T, Tsuruta O, Sano Y, Yamano H, Shimizu S, Yahagi N, Watanabe T, Nakamura H, Fujii T, Ishikawa H, Sugihara K; Colorectal Endoscopic Resection Standardization Implementation Working Group of the Japanese Society for Cancer of the Colon and Rectum, Tokyo, Japan. Local recurrence after endoscopic resection for large colorectal neoplasia: a multicenter prospective study in Japan. Am J Gastroenterol. 2015 May;110(5):697-707. doi: 10.1038/ajg.2015.96. Epub 2015 Apr 7.
• Fuccio L, Repici A, Hassan C, Ponchon T, Bhandari P, Jover R, Triantafyllou K, Mandolesi D, Frazzoni L, Bellisario C, Bazzoli F, Sharma P, Rosch T, Rex DK. Why attempt en bloc resection of non-pedunculated colorectal adenomas? A systematic review of the prevalence of superficial submucosal invasive cancer after endoscopic submucosal dissection. Gut. 2018 Aug;67(8):1464-1474. doi: 10.1136/gutjnl-2017-315103. Epub 2017 Dec 5.
• Yoshida M, Kakushima N, Mori K, Igarashi K, Kawata N, Tanaka M, Takizawa K, Ito S, Imai K, Hotta K, Ishiwatari H, Matsubayashi H, Ono H. Learning curve and clinical outcome of gastric endoscopic submucosal dissection performed by trainee operators. Surg Endosc. 2017 Sep;31(9):3614-3622. doi: 10.1007/s00464-016-5393-9. Epub 2016 Dec 30.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: February 4, 2025
• First Submitted That Met QC Criteria: February 4, 2025
• First Posted (Actual): February 7, 2025

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Endoscopic Mucosal Resection (EMR); Endoscopic submucosal dissection (ESD); Laterally spreading tumors (LST)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures; Diagnostic Techniques, Surgical; Endoscopy, Gastrointestinal; Endoscopy, Digestive System; Diagnostic Techniques, Digestive System; Endoscopy; Digestive System Surgical Procedures; Endoscopic Mucosal Resection
• Other Study ID Numbers: 104/2021/SPER/IRCCSRE

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
• product manufactured in and exported from the U.S.: No