SCar-biopsies After Malignant Colorectal Polypectomy of Uncertain RAdicality

Study Overview
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Brief Summary
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After endoscopic removal of a colorectal polyp that harbors (unexpected) adenocarcinoma, pathology usually can not guarantee a radical resection from an oncological point of view. In such case, additional surgical resection is advised. However, only in 15% of patients, residual adenocarcinoma is found. This study investigates the sensitivity of biopsies from the polypectomy scar for residual adenocarcinoma.

Detailed Description
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Rationale: colorectal polyps may harbor adenocarcinoma. Numbers are increasing due to the nationwide colorectal screening program. After endoscopic removal, rescue surgery is often performed because radicality can not be guaranteed by the pathologist. However, in 85% of surgical specimen no residual malignancy is found. Given morbidity and mortality associated with surgery a method to diagnose residual cancer is needed. Biopsies from the polypectomy site are variably used to reduce the likelihood of residual tumor at the polypectomy site under these circumstances. However, the sensitivity of such biopsies is unknown. Objective: to evaluate the sensitivity of second-look endoscopic biopsies from the polypectomy site for residual tumor. Study design: prospective cross-sectional design using a multi-center approach. Study population: patients planned for rescue surgery for the sole reason of (potentially) irradical endoscopic resection of a colorectal adenocarcinoma without poor differentiation, lymphovascular invasion or tumor budding and without other signs of dissemination. Intervention: endoscopic biopsies from the polypectomy site before operation. Main study parameters/endpoints: sensitivity of second-look biopsies from the polypectomy site for residual tumor in the resected bowel and postoperative mortality. Various other factors will be assessed that might be associated with residual cancer. Nature and extent of the burden and risks associated with participation and benefit: Depending on the situation: a): In case a tattoo needs to be done of the polypectomy site, a second endoscopy is done anyway and taking biopsies (painless) will be of no extra burden; b): In case no tattoo needs to be done a sigmoidoscopy (lesion distal to the splenic flexure) or colonoscopy (proximal to the splenic flexure) needs to be arranged for the purpose of this study. A sigmoidoscopy takes 10-20 minutes. Preparation consists of two enemas. A colonoscopy takes 20-30 minutes. Preparation consists of drinking 3 litre of MoviPrep®, both usually doe at home. Notice that the patient has recent experience with colonoscopy. If necessary, both investigations can be arranged under conscious sedation (the rule in colonoscopy), which also implies day-care admission. The risk of complications of a second endoscopy is estimated < 1:5000. The benefit of a 2nd colonoscopy is the discovery of new polyps in 10-25% of cases.

Official Title
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The Sensitivity of Scar-biopsies for Residual Colorectal Adenocarcinoma After Endoscopic Resection With Uncertain Radicality

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Procedure: Flexible sigmoidoscopy or colonoscopy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 or above. Endoscopically removed colorectal lesion with the following pathological characteristics: A moderately-to-well differentiated adenocarcinoma. If possible to judge: distance between adenocarcinoma and vertical or lateral resection margin is less than 1 mm. In case of piecemeal resection: unjudgeable radicality (mostly due to loss of orientation and multiple fragments). Absence of / unjudgeable lymphatic / vascular invasion. No or only grade I tumor budding. No suspicion of dissemination on the following investigations: serum carcino-embryonic antigen, a computer tomographic (CT) scan of the abdomen and a chest X-ray; in case of a rectal tumor (less than 15 cm from the anal verge): an additional magnetic resonance imaging of the rectum. Operation is advised in agreement with the Dutch Guideline on Colorectal cancer, planned and agreed on by the patient. Written informed consent is obtained. Exclusion Criteria: Pathology shows one or more of the following characteristics: A radical en-bloc resection with a free vertical and lateral margin of ≧ 1 mm. A poorly differentiated or signet-cell containing adenocarcinoma. Lymphatic or vascular invasion (if this feature is unjudgeable due to piecemeal resection, no exclusion is done). Tumor budding grade II-III. Suspicion of dissemination on investigations as mentioned in the inclusion criteria. Patients already receiving anti-tumor treatment for another tumor or a synchronic colorectal cancer. Patients in whom a second-look endoscopy would require major and unacceptable effort and / or resources, for instance clinical admission for bowel preparation, long travel, general anesthesia, extremely difficult to reach polypectomy site. Such at the decision of the patient and / or treating physician. Patient is planned for trans-anal surgery. Patient is not planned for surgery. Patient is pregnant. Patient does not provide written informed consent or is unable to provide such.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Flexible sigmoidoscopy or colonoscopy<br>Subjects will undergo these investigation to take biopsies from the polypectomy scar. | Procedure: Flexible sigmoidoscopy or colonoscopy<br>* Depending on the localization of the scar of the malignant polyp, either a flexible sigmoidoscopy or colonoscopy will be done to take biopsies from the polypectomy scar.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of biopsies for residual cancer | The number of patients with endoscopic biopsies containing adenocarcinoma divided by the number of patients with adenocarcinoma in the resected specimen. | up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 90-day mortality after rescue surgery | The number of patients that died within 91 day after the operation for presumed residual adenocarcinoma. | 91 days from surgery | 
| The sensitivity of biopsies for residual cancer in the bowel wall | The number of patients with endoscopic biopsies containing adenocarcinoma divided by the number of patients with adenocarcinoma in the resected bowel wall (regardless of regional lymph nodes) | up to 1 year | 
| The number of complications (defined according to GCP) after biopsies from the polypectomy scar | The number of patients with bleeding or perforation after taking biopsies from the polypectomy scar, requiring at least prolongation of treatment, or admission to hospital, or delay or speeding up of surgery. | up to 30 days | 
| The sensitivity of global endoscopic assessment of polypectomy site for residual cancer at initial and follow-up endoscopy (to take scar biopsies) | The number of patients in whom the endoscopic resection initially and/or at follow-up endoscopic was assessed as incomplete and who also have residual cancer in the surgically resected specimen divided by the total number of patients in whom the endoscopic resection was judged to be incomplete. | up to 1 year | 
| The proportion of patients with residual cancer in the resected specimen if malignancy was unsuspected during the endoscopic polypectomy | The number of patients in whom the malignancy was initially unsuspected during endoscopic polypectomy and who also have residual cancer in the surgical specimen divided by the total number of patients in whom the malignancy was initially unsuspected during endoscopic polypectomy. | up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endoscopic resection, Pathology, Rescue surgery