ESD for Colorectal LSL Using a Selective Strategy - a Prospective Cohort Study

Study Overview
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Brief Summary
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Colonic Laterally spreading lesions (LSL) => 20mm are at high risk to progress to cancer. Overt stigmata of submucosal invasive cancer (SMIC) has been well characterized and includes ulceration and surface pit pattern changes as per the Kudo classification of type V. In a recent report, risk factors for LSL with SMIC and no overt stigmata (i.e. covert SMIC) were described. Resection of these lesions 'en-bloc' can allow for better histological staging and potentially reduce the need for surgical resection.

Detailed Description
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With over 14,000 patients diagnosed annually, colorectal carcinoma (CRC) is the second most frequently invasive malignancy in Australia. By not only diagnosing CRC at an early stage, but also removing precursor adenomas, colonoscopy with polypectomy reduces the risk of developing and dying from CRC. Laterally spreading lesions >= 20mm (LSL) are more likely to progress to cancer. The prevalence of LSL ranges from 1-5% in screening population. The risk of malignant progression of colorectal adenomas found during colonoscopy increases with lesion size, i.e. the cancer preventive effect is likely to be maximal in large lesions. Patients with LSL have a higher risk of malignancy and a higher recurrence rate of adenoma after lesion removal compared with diminutive polyps. Endoscopic imaging can now accurately predict LSL with submucosal invasive cancer (SMIC) through assessment of LSLs morphology (Paris classification, granularity) and surface pit-pattern (Kudo classification). Such cases can be considered to have LSL with overt risk of SMIC. Recent publication has highlighted that some LSLs might hrbor SMIC without overt morphological features (i.e. high risk for covert SMIC). These LSL with high risk of covert SMIC stratified LSLs based on lesion location and lesion morphology. Generally LSLs can be safely and effectively removed by wide field endoscopic mucosal resection (WF-EMR) in over 90% of cases in competent hands. One of the draw backs with WF-EMR is it requires piecemeal resection and thus is limited in providing assessment of complete excision and depth of submucosal invasion in cases where SMIC is present. Thus, endoscopic en-bloc resection is preferable from an oncologic standpoint to obtain a single specimen for proper histopathologic assessment. Endoscopic submucosal dissection (ESD) is a technique that is now becoming the preferred method for achieving a complete endoscopic and histologic resection, referred to as R0. Evidence from retrospective cohort and meta-analyses suggests ESD provides a more consistent oncologic resection with a reduced rate of recurrence. However, the major limitations with the technique relate to increased procedure time and the skill-set required for performing the procedure. One of the other major limitations of ESD is significant cost associated with the procedure, which includes procedure time and additional equipment in addition to the treatment of any subsequent complications. As such the implementation of ESD as the standard of care for all colorectal lesions has not been undertaken in Western countries, however it may have an important role for selective cases especially where there is concern for sub-mucosal invasive cancer (SMIC). The investigators propose a selective ESD strategy to be performed for patients focusing on overt evidence of SMIC and those at high risk of covert SMIC (defined as risk >10%). The investigators will follow a prospective cohort study assessing the use of selective ESD strategy in the colorectum in the Western population.

Official Title
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Endoscopic Submucosal Dissection for Sessile Polyps and Laterally Spreading Lesions of the Colorectum Using a Selective Strategy - a Prospective Cohort Study

Conditions
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Colorectal Neoplasm, Endoscopic Mucosal Resection

Intervention / Treatment
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* Procedure: Endoscopic Submucosal Dissection
* Procedure: Endoscopic Mucosal Resection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients referred for colorectal resection of large laterally spreading lesions in colon. Can give informed consent to trial participation Exclusion Criteria: Previous resection or attempted resection of target adenoma lesion Endoscopic appearance of invasive malignancy Age less than 18 years Pregnancy Active Inflammatory colonic conditions (e.g. inflammatory bowel disease) Use of anticoagulant or antiplatelet agents other than aspirin outside of internationally recognised guidelines American Society of Anesthesiology (ASA) Grade IV-V

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Selective treatment algorithm of ESD or EMR according to risk stratification.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ESD<br>Lesion with overt stigmata of SMIC or those with high risk (=> 10%) for covert SMIC. | Procedure: Endoscopic Submucosal Dissection<br>* Endoscopic Submucosal Dissection (ESD) results in en-bloc resection of LSL, regardless of lesion size. This allows for accurate histopathological assessment of SMIC, R0/R1 resection and depth of invasion. ESD is considered a potentially curative for superficial cancers (T1a).<br>* Other names: ESD;|
| Active Comparator: EMR<br>Lesion with no overt or a low risk for (<10%) for covert SMIC | Procedure: Endoscopic Mucosal Resection<br>* EMR is the current standard for treating colonic LSL and has been validated to be safe and efficacious. LSLs => 20mm are frequently resected piecemeal. Recent research show that resection margin soft coagulation reduces recurrence rates to those similar to en-bloc resections.<br>* Other names: EMR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of surgical referral | Incidence of surgical referral due to non-curative endoscopic resection. | 3 months post procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R0 resection rate | Rate of en-bloc resection with clear resection margins. | 3 months post procedure | 
| En Bloc resection rate | Rate of en-bloc resection | 3 months post procedure | 
| Technical success rate | Rate of procedures completed as per protocol | 3 months post procedure | 
| Duration of procedure | Procedure duration in minutes. | procedure | 
| Adenoma recurrence rate | Rate of recurrent adenoma at resection site on follow-up. | 3 years post procedure |