Follow-up Protocol of Colorectal Endoscopic Mucosal Resection Scars

Study Overview
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Brief Summary
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Nowadays endoscopic mucosal resection (EMR) is the gold standard for the removal of large laterally spreading and sessile colorectal lesions ≥ 20 mm. However, recurrence rate after successful EMR (defined by the absence of neoplastic tissue at the completion of the procedure after careful inspection of the post-EMR mucosal defect and margin) is about 15-20%. Consequently, current guidelines recommend a surveillance colonoscopy between 4 and 6 months after resection for detection of residual or recurrent polyp. There are few studies that have examined the accuracy of advanced endoscopic imaging for the prediction of histological recurrence but none of these imaging modalities have been validated for surveillance after EMR. Therefore, current guidelines strongly recommend systematic biopsy of EMR scar. The main aim of this study is to assess the incremental benefit of narrow band imaging (NBI) and white light endoscopy (WLE) randomizing the initial technique for the endoscopic detection of post-EMR recurrence and to asses if this advanced imaging method achieve sufficient diagnostic accuracy to exclude recurrence without the need for biopsy.

Detailed Description
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a. Study type: multicenter randomized crossover trial: i. prospective inclusion of consecutive patients undergoing first follow-up surveillance colonoscopy after successful EMR of colorectal lesion; ii. crossover randomization by computer generated tables; iii. allocation concealment by sealed, opaque envelopes; iv. pathologist-blinded - pathologists are blinded to the study protocol and samples are received as 'EMR scar for assessment' . b. Selection patient method: inclusion by invitation of patients undergoing the first follow-up surveillance colonoscopy after successful EMR of colorectal lesion. c. Sample size: 210 (two groups of 105 patients). To improve accuracy from 85% (value obtained by a study that did not show significant differences in the accuracy of NBI followed by WLE vs. WLE followed by NBI) to 95% and assuming a normal distribution and a power of 80% (α=0.05), the calculated sample size of each of the 2 groups was 96; allowing for a 10% dropout rate, the sample size is 105 per group (210 patients overall). d. Procedures and data collection methods: i. Each procedure is performed by the same endoscopist. ii. All patients receive split dose bowel preparation. iii. All colonoscopies are performed using high definition colonoscopes with NBI ( EVIS EXERA III CV 185 and CV 190; Olympus Inc., Tokyo, Japan). iv. Colon inspection is done with WLE during withdrawal. v. At the proximity of the scar WLE and NBI were used randomly one after the other (WLE>NBI or NBI>WLE). If NBI is the first technique used, it is switched prior to scar detection, avoiding, as far as possible, a glance with WLE. The edges of the scar are interrogated followed by the centre of the scar and finding are recorded. vi. After both evaluations, if there is no suspicion of recurrence, the site is sampled by at least 2 biopsies of the scar edge. If there is any suspicion of recurrence, tissue sample is obtained and then treated by endoscopic resection using standard methods. At least 2 biopsies specimens from normal appearing scar are also obtained. e. Analysed variables: i. patient characteristics; ii. data from baseline colonoscopy; iii. data from first surveillance colonoscopy (see outcome measures). f. Statistical analysis: i. Performed using statistical software IBM SPSS Statistics, Version 25.0. Armonk, NY: IBM Corp. ii. Continuous variables are reported as mean and standard deviation or median and interquartile range, if they have normal or not normal distribution, respectively; categorical variables as absolute and relative frequency. iii. Continuous variables are compared between two groups using Student's T test if they have a normal distribution and homogeneity of variance or Mann-Whitney U if these conditions are not met. Categorical variables are compared using Pearson's X2 test or Fisher test. iv. Sensitivity, specificity, negative and positive predictive values and accuracy are calculated using 2x2 contingency tables. v. All hypotheses are two-tailed and a P-value<0.05 is considered statistically significant.

Official Title
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Follow-up Protocol of Colorectal Endoscopic Mucosal Resection Scars: a Multicentre Randomized Single-blinded Crossover Trial

Conditions
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Colorectal Cancer, Recurrence, Local Neoplasm

Intervention / Treatment
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* Diagnostic Test: WLE followed by NBI or NBI followed by WLE (crossover design)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients undergoing the first follow-up surveillance colonoscopy after successful EMR of colorectal lesion. Exclusion Criteria: informed consent not provided, inflammatory bowel disease, inadequate bowel preparation (Boston Bowel Preparation Scale total score < 6 or < 2 in a segment), EMR scar not identified during colonoscopy, tissue acquisition unfeasibly.

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: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A: WLE followed by NBI<br>EMR scar is interrogated using WLE followed by NBI | Diagnostic Test: WLE followed by NBI or NBI followed by WLE (crossover design)<br>* EMR scar is inspected using WLE followed by NBI or vice versa<br>* Other names: WLE followed by NBI or NBI followed by WLE;|
| Active Comparator: Group B: NBI followed by WLE<br>EMR scar is interrogated using NBI followed by WLE | Diagnostic Test: WLE followed by NBI or NBI followed by WLE (crossover design)<br>* EMR scar is inspected using WLE followed by NBI or vice versa<br>* Other names: WLE followed by NBI or NBI followed by WLE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic performance of WLE and NBI for each group | Sensitivity, specificity, negative predictive value, positive predictive value and accuracy of NBI and WLE for each group calculated using 2x2 contingency tables | 1 day (at the time of data analysis) | 
| Recurrent adenoma - WLE | WLE recurrent adenoma identification for each group | 1 day (during colonoscopy) | 
| Recurrent adenoma - NBI | NBI recurrent adenoma identification for each group | 1 day (during colonoscopy) | 
| Recurrent adenoma - histology | Adenoma recurrence confirmed by histology | 1 day (within 30 days from colonoscopy) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lesion characterization at the baseline colonoscopy | Lesion size and location, Paris classification, NICE classification, number of pieces, use of adjunctive ablative techniques and those identification and histology. Data collected by endoscopic reports consultation | 1 day (at the time of patient inclusion) | 
| Scar characterization at the first surveillance colonoscopy | Scar size, presence or absence of recurrence, in case of recurrence: number of sites, location (edge of the scar, within the scar or both), morphology of recurrence, NICE classification (for NBI evaluation) | 1 day (immediately after first surveillance colonoscopy) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrence, endoscopic mucosal resection, colorectal lesions, advanced endoscopic imaging