Reducing Neoplasia Recurrence After Non-thermal Endoscopic Resection of Large Colorectal Polyps (COSA-RCT)

The goal of this clinical trial is to clarify the role of adjuvant thermal ablation for non-thermal endoscopic mucosal resection (EMR) of large (≥20mm) flat colorectal polyps (so-called laterally spreading lesions [LSLs]).

The hypothesis is that adding adjuvant thermal ablation to non-thermal EMR (vs no ablation) will result in lower lesion recurrence rates at 6-month follow-up, and non-inferior adverse events (AE) rates 14 days post EMR.

For participants with planned EMR, endoscopists will perform non-thermal EMRs as per standard of care and:

• adjuvant thermal ablation will either not be performed (control group), or will be applied to the base and outside margins of the resection site (experimental group);
• then, all patients will be contacted 14-44 days after EMR, to verbally ascertain the occurrence of AEs;
• then, all patients will undergo a first follow-up colonoscopy at 6 months after initial conoloscopy to assess lesion recurrence;
• finally, all patients will undergo a second and final colonoscopy 18 months after EMR.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer; Polyp of Colon
• Intervention / Treatment: Procedure: Adjuvant thermal ablation; Procedure: No adjuvant thermal ablation

Detailed Description

This trial is an open-label, two-arm, parallel-group, multicenter RCT with co-primary outcomes (superiority for recurrence, non-inferiority for AEs). Patients undergoing non-thermal EMR will be randomized (1:1) to adjuvant thermal ablation (experimental group) or no ablation (control group).

All participating endoscopists will view dedicated teaching videos of the standard thermal ablation technique and key technical details to ensure consistent study procedures. Patients with planned EMR procedures will be invited by a research assistant before the EMR to participate in the study. Patients will be randomized to control or experimental groups in a 1:1 ratio using a central REDCap randomization module after the EMR resection phase is completed and immediately before adjuvant thermal ablation (intervention). This will limit bias by ensuring that the EMR technique is not affected by group allocation. When 2 or more lesions are present in a patient, the largest lesion will be chosen for inclusion in the study and all lesions will be photodocumented for auditing purposes.

No ablation (control group): Non-thermal EMR will be performed as per standard of care with submucosal injection and non-electrocautery resection of all visually visible polyp tissue using a snare. When the endoscopist determines that the resection is complete, no adjuvant thermal ablation of the post-EMR defect will be performed. Defect closure using clips will be performed only if there is concern for injury to the muscle layer or signs of overt perforation. A tattoo will be placed 3 cm distal to the resected lesion to allow for better identification of the resection site for follow-up. If multiple large polyps are found and removed, the largest lesion (study polyp) will be marked with two tattoos 3 cm distally and 3 cm proximally, to clearly identify the study polyp resection site.

Adjuvant thermal ablation (experimental group): Non-thermal EMR will be performed as per standard of care with submucosal injection and non-electrocautery resection of all visually visible polyp tissue using a snare. When the endoscopist determines that the resection is complete, submucosal injection (0.9% NaCl with methylene blue solution) using the h-APC probe (ERBEJET 2 attached to Vio3 electrosurgical unit, pressure: 40 bar) will be performed to further expose the resection margin. Adjuvant thermal ablation will be applied to the outside margins of the resection site using the h-APC probe. Then, adjuvant thermal ablation will also be applied to the base of the resection site using the h-APC probe. The precise electrocautery mode (PRECISE-APC setting 9) will be used to apply thermal ablation, as previously described for h-APC. Defect closure using clips will be performed only if there is concern for injury to the muscle layer or signs of overt perforation. A tattoo will be placed in the same way as described in the control group and, again, if multiple large polyps are found and removed, the largest lesion (study polyp) will be marked with two tattoos 3 cm distally and 3 cm proximally, to clearly identify the study polyp resection site.

At 6 months after initial colonoscopy, patients will undergo a first follow-up colonoscopy, as suggested by current guidelines and from studies showing that most recurrences occurred within the first 6 months. A window of 3 to 13 months will be permitted for the first follow-up. If recurrence is detected, patients will undergo subsequent colonoscopies at shortened intervals, as determined by the treating endoscopist, until no recurrence is detected. If surgery is performed due to difficulty in treating recurrence, patients will undergo a follow-up colonoscopy 6 months after surgery to detect any possible recurrence. All patients will undergo a second and final study colonoscopy 18 months after randomization, which will also mark the end of study follow-up. The second follow-up may be conducted within a window of 14 to 24 months. Subsequent colonoscopies will then be recommended outside the study as per routine care for such a clinical situation.

• Study Type: Interventional
• Enrollment (Estimated): 752
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada
      • Centre Hospitalier de l'Universite de Montreal
      • Principal Investigator: Daniel von Renteln, MD
      • Contact: Samira Hanin; Phone Number: 30916 514-890-8000; Email: samira.hanin.chum@ssss.gouv.qc.ca

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adult patients
• Undergoing EMR for large (≥20 mm) colorectal LSL
• Providing written and informed consent for study participation

Exclusion Criteria:

• Inflammatory bowel disease
• Non-elective colonoscopy
• Poor general health (American Society of Anesthesiologists classification >III)
• Coagulopathy or thrombocytopenia (international normalized ration ≥1.5 or platelets <50*10^9/L)
• Bulky lesions (granular mixed with ≥10mm module).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Endoscopic mucosal resection (EMR) + adjuvant thermal ablation; Adjuvant thermal ablation will be applied to the base and outside margins of the resection site after non-thermal EMR.	Procedure: Adjuvant thermal ablation; When the endoscopist determines that the resection is complete, submucosal injection (0.9% NaCl with methylene blue solution) using the h-APC probe (ERBEJET 2 attached to Vio3 electrosurgical unit, pressure: 40 bar) will be performed to further expose the resection margin. Adjuvant thermal ablation will be applied to the outside margins of the resection site using the h-APC probe. Adjuvant thermal ablation will then also be applied to the base of the resection site using the h-APC probe. The precise electrocautery mode (PRECISE-APC setting 9) will be used to apply thermal ablation, as previously described for h-APC.
Active Comparator: Endoscopic mucosal resection (EMR); After non-thermal EMR, no adjuvant thermal ablation will be performed.	Procedure: No adjuvant thermal ablation; After performing non-thermal EMR with thermal ablation, adjuvant thermal ablation will not be performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lesion recurrence rate	Defined as the number of cases with pathology-confirmed hyperplastic, serrated, or adenomatous histology at the tattooed resection site compatible with the study polyp histology divided by the total number of cases.	6 months
Clinically significant adverse event (AE) rate	Defined as the number of cases with delayed bleeding (blood per rectum resulting in emergency room visit, unplanned hospitalization, endoscopic, radiologic, or surgical intervention) and/or delayed perforation (endoscopic or radiologic evidence of significant air or any luminal contents outside the gastrointestinal tract) divided by the total number of cases.	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Any delayed bleeding rate	Defined as the number of cases with blood per rectum, regardless of clinical significance, divided by the total number of cases.	14 days
Lesion recurrence rate at 18-month follow-up	Defined as the number of cases with pathology-confirmed hyperplastic, serrated, or adenomatous histology at the tattooed resection site compatible with the study polyp histology divided by the total number of cases.	18 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
High-grade dysplasia rate at the 18-month follow-up	Defined as the number of cases with high-grade dysplasia on resection scars divided by the total number of cases.	18 months
Rate of CRC during the 18-month follow-up period	Defined as the number of cases with pathology-confirmed carcinomas divided by the total number of cases.	From enrollment to the final follow-up colonoscopy at 18 months
Colonoscopies to lesion clearance	Defined as the total number of colonoscopies required to achieve lesion clearance, which means no histologic recurrence at the resection scar on follow-up.	18 months
EMR procedure time	Defined as the length of time required for the initial EMR.	1 day
Rate of delayed bleeding in the proximal colon	Number of cases with clinically significant delayed bleeding in the proximal colon (proximal to the splenic flexure) divided by the total number of cases.	14 days
Defect closure time	Time required for defect closure.	1 day
Rate of technical success for complete defect closure	Number of cases with technical success for complete defect closure (defined as adequate apposition of the mucosal defect margins without visible submucosal areas >3mm along the closure line) divided by total number of cases.	6 months
Costs associated with procedures	Total costs required to perform non-thermal EMR with adjuvant thermal ablation or without ablation.	From enrollment to the final follow-up colonoscopy at 18 months

Collaborators and Investigators

• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2025
• Primary Completion (Estimated): May 1, 2031
• Study Completion (Estimated): May 1, 2032

Study Registration Dates

• First Submitted: November 17, 2025
• First Submitted That Met QC Criteria: November 17, 2025
• First Posted (Actual): November 21, 2025

Study Record Updates

• Last Update Posted (Actual): November 21, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Pathological Conditions, Anatomical; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Polyps; Intestinal Polyps; Pathological Conditions, Signs and Symptoms; Colorectal Neoplasms; Colonic Polyps
• Other Study ID Numbers: 2026-13165

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures and appendices).
• IPD Sharing Time Frame: Beginning 12 months and ending 36 months following article publication.
• IPD Sharing Access Criteria: Proposals should be directed to daniel.von.renteln.med@ssss.gouv.qc.ca. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No