Delayed Surveillance Colonoscopy Following Piecemeal EMR - a Randomized Study
Phase: NA
Conditions: Colon Cancer Prevention, Polyp Colorectal
Sponsor: Rambam Health Care Campus

Delayed Surveillance Colonoscopy following 
Piecemeal EMR – a Randomized Study 
 
 
 
 
Study approval Number- RMB-0069-25 
Document Date- 17/12/2025 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Abstract 
Background 
Colorectal cancer (CRC) is a major cause of cancer-related morbidity and 
mortality. Piecemeal endoscopic mucosal resection (pEMR) is an effective 
treatment for large non-pedunculated colorectal polyps (LNPCPs), which are 
high-risk precursors of CRC. Previous data have shown that residual and 
recurrent adenoma (RRA) may occur in 15–30% of cases following pEMR. 
Accordingly, current guidelines recommend intensive follow-up, which can 
cause patient morbidity and lack of compliance and financial healthcare 
burdens. Recent advances in EMR techniques, particularly margin ablation, 
have significantly reduced RRA rates to approximately 5%. In a recent 
retrospective analysis, we found that delayed surveillance (12 months post-
EMR) was not associated with higher recurrence rates compared to early 
surveillance (3–6 months). This prospective randomized trial aims to confirm 
and validate these findings. 
Objectives and Hypotheses 
To evaluate whether a relaxed surveillance strategy involving fewer 
colonoscopies (12 and 48 months) is non-inferior to the standard intensive 
strategy (6, 18, and 48 months) in management of residual or recurrent 
disease. 
Hypothesis: A relaxed surveillance protocol does not increase the rate of 
residual or recurrent adenoma detected at long-term follow-up, in patients 
undergoing pEMR of LNPCPCs with margin ablation. 
Methods 
This multicenter prospective randomized controlled trial will enroll 
approximately 760 patients undergoing pEMR for LNPCPs at Rambam Health 
Care Campus, Tel Aviv Sourasky Medical Center (Ichilov Hospital), Nazareth 
Holy Family Hospital and HaEmek Medical Center (Afula). Detailed clinical, 
endoscopic, and histologic data will be collected on lesion morphology, size, 
histopathology, and procedural techniques. 

Patients will be randomized into two surveillance groups: the Standard 
Surveillance Group: Colonoscopies at 6, 18, and 48 months after the index 
procedure and the Relaxed Surveillance Group: Colonoscopies at 12 and 
48 months after the index procedure (similar to surveillance protocols 
following en-bloc excision by ESD) 
Significance and Relevance to Cancer Care 
This study directly addresses a major clinical question in post-polypectomy 
surveillance: whether all patients require early intensive follow-up after 
piecemeal EMR. If the relaxed surveillance approach proves non-inferior, it 
may support a revision of current guidelines. This would result in fewer 
colonoscopies, reduced burden on patients and health systems, improved 
adherence, and lower costs—without compromising oncologic safety. The 
findings of this trial may contribute to the development of more efficient and 
personalized follow-up strategies in colorectal cancer prevention, with the 
potential to influence future clinical practice guidelines and national health 
policy. 
 
 
 
 
 
 
 
 
 
 
 
 

Background and Aim 
Colorectal cancer (CRC) is among the most common cancers globally, with 
significant morbidity and mortality [1]. Numerous studies have demonstrated 
that removing colorectal polyps reduces the incidence and mortality of CRC 
[2]. Large non-pedunculated colorectal polyps (LNPCPs) are considered high-
risk precursors of colorectal cancer. Piecemeal endoscopic mucosal resection 
(pEMR) is the recommended treatment for most non-invasive LNPCPs 
according to societal guidelines, due to its excellent safety and efficacy profile 
[3,4,5,6]. 
One major drawback of colonic pEMR is the potential for residual and 
recurrent adenoma (RRA). Studies have shown that RRA occurs in 15-30% of 
cases, with risk factors including high-grade dysplasia, lesion size, lesion 
location, intra-procedural bleeding, and previous attempts at removal [7,8,9]. 
Recurrence at the first surveillance colonoscopy (SC1) can be identified 
endoscopically with high accuracy [10], and endoscopic treatment during 
SC1, which includes re-excision of the RRA with or without ablation, results in 
a very low residual RRA rate (2%-4%) at the second surveillance colonoscopy 
(SC2) [7]. 
Recent data suggests that RRA can be significantly reduced by systematically 
applying ablative measures to the post-EMR resection margin. Multiple 
studies show that in expert hands, the risk of RRA at SC1 can be reduced to 
3-5% [6,7,8,12,13]. Currently, an intensive follow-up schedule is 
recommended following pEMR, with SC1 performed 3-6 months after the 
initial procedure and SC2 one year after SC1. However, this intensive follow-
up places additional burdens on both patients and the healthcare system and 
may hinder patient compliance [9]. Given that with the advent of margin 
ablation, RRA rates at SC1 are extremely low, the impact of early surveillance 
on long-term recurrence rates may be minimal. 
We recently completed a retrospective study to evaluate this hypothesis. The 
study showed no significant difference in recurrence rates between the 
standard group, which underwent surveillance after 3-6 months, and a group 
of patients who had delayed surveillance (mean follow-up of 11 months). 

The aim of this study is to confirm and validate these findings, in a prospective 
randomized study. This will solidify the results we observed in our previous 
retrospective study and potentially lead to a less intensive surveillance 
strategy. 
Methods 
Study Design: 
We will conduct a multicenter, prospective, non-inferiority randomized study in 
four academic centers in Israel: Rambam Health Care Campus, Tel Aviv 
Sourasky Medical Center (Ichilov Hospital), Nazareth Holy Family Hospital 
and HaEmek Medical Center. Following complete pEMR of a LNPCP, 
participants will be randomly assigned to either the standard surveillance 
protocol or the relaxed surveillance protocol. Patients will be consented prior 
to the EMR procedure. 
Randomization – computer-generated dynamic block randomization with a 1:1 
allocation ratio will be performed to achieve balance of multiple baseline 
covariates including: demographic data, procedural data, and lesion 
characteristics. 
Patients: 
We will include adult patients who undergo pEMR for LNPCPs (≥20 mm) and 
provide informed consent. Inclusion criteria include 
• Adults aged 18 years and older. 
• Undergoing pEMR of LNPCPs. 
• Able to provide informed consent and comply with follow-up 
requirements. 
Exclusion criteria include: 
• Patients with invasive cancer identified during the index procedure. 
• en bloc resection. 
• Patients unable to attend follow-up colonoscopies due to comorbid 
conditions. 

• Patients who require additional surgery for polyp removal or other 
complications. 
Informed Consent: 
Before enrollment, each patient will receive a detailed explanation about the 
study. They will be given the opportunity to ask questions and discuss any 
concerns. Written informed consent will be obtained from all participants prior 
to any study-related procedures. 
Procedures: 
All pEMR procedures and surveillance colonoscopies will be performed by 
experienced endoscopists trained in pEMR techniques. Specifically, A.K. was 
lead author on the randomized trial on margin ablation [13] and practiced this 
technique routinely since early 2016. Procedures will be conducted using 
high-definition endoscopes (Olympus 190 series Q190 PCF/CF or Fuji 760 
series), following a standardized protocol: 
1. Inspection and photo documentation of LNPCPs with high-definition 
white light (HDWL) and optical chromoendoscopy before resection to 
exclude features suggestive of deep submucosal invasion. 
2. Standard pEMR technique with the objective of complete snare 
excision, using sub-mucosal injections of Succinilated Gelatine 
(Gelofusin) or Normal Saline and braided snares of various sizes. 
3. Thermal ablation of the mucosal defect margin using snare soft tip 
coagulation (STSC) to create a 2- to 3-mm rim of ablated tissue. 
Groups and Follow-Up: 
• Standard Surveillance Group: Patients will undergo surveillance 
colonoscopy at 6 and 18 months after the index procedure. The 
standard surveillance group will have an additional colonoscopy at 48 
months in order to converge the timeline with the delayed group. 
• Relaxed Surveillance Group: Patients will undergo surveillance 
colonoscopy at 12 and 48 months after the index procedure. 
 
 

Data Collection: 
We will collect demographic data, lesion characteristics, procedural details, 
and surveillance outcomes. All recurrences will be identified using endoscopic 
evaluation. Routine biopsies will be taken only when recurrence is suspected 
endoscopically, based on a validated approach that has shown a negative 
predictive value (NPV) of 99% for identifying normal scars without recurrence 
[14]. 
Data Management, Storage and Security: 
All data will be collected on data collection forms. These will be stored in a 
locked cabinet at the Gastroenterology department. This data will be entered 
into electronic data sheets (Excel and Redcap). The electronic files will be 
password protected and stored on a password-protected computer in the 
Gastroenterology department. Access to the data will be given to the study 
investigators and the study research assistant. 
Primary Endpoint 
The primary endpoint is the rate of residual or recurrent adenoma at the 
second surveillance colonoscopy (SC2), comparing the relaxed and standard 
surveillance groups. 
Secondary Endpoints 
Secondary endpoints include: recurrence rates at SC1; risk factors associated 
with recurrence; subgroup analysis of high risk lesions (e.g., high-grade 
dysplasia, sessile serrated morphology); rates of new or missed polyps at 
SC2; adverse events related to EMR or surveillance procedures; and 
comparative cost effectiveness of both surveillance strategies. 
Timetable 
We anticipate 4-5 years are required to complete the study: 1-2 years for 
recruitment and an additional 36 months for follow-up to SC2. 
Funding and Competing Interests 

There are no disclosures. No commercial funding is sought. We will apply for 
research grants to help with study funding, specifically research assistant 
salary and management of the electronic database. 
 
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