SCar-biopsies After Malignant Colorectal Polypectomy of Uncertain RAdicality

Colorectal Cancer Clinical Trial

— SCAPURA  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02328664
• Other study ID #: SCAPURA-Study
• Status: Terminated
• Phase: N/A
• Start date: August 2015
• Est. completion date: May 2019

Study information

• Verified date: December 2019
• Source: Deventer Ziekenhuis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 246
• Est. completion date: May 2019
• Est. primary completion date: May 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Procedure:
• Flexible sigmoidoscopy or colonoscopy
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.

Locations

Country	Name	City	State
Netherlands	Meander Medical Center	Amersfoort	Utrecht
Netherlands	Academical Medical Center, Gastroenterology department	Amsterdam	Noord-Holland
Netherlands	Medical Center Slotervaart	Amsterdam	Noord-Holland
Netherlands	Onze Lieve Vrouwe Gasthuis (Oost & West)	Amsterdam	Noord-Holland
Netherlands	The Netherlands Cancer Institute Antoni van Leeuwenhoekhuis	Amsterdam	Noord-Holland
Netherlands	Gelre Hospitals	Apeldoorn	Gelderland
Netherlands	Medical Center de Veluwe	Apeldoorn	Gelderland
Netherlands	Maasstad Hospital Pantein	Beugen	Noord-Brabant
Netherlands	Amphia Hospital	Breda	Noord-Brabant
Netherlands	IJsselland Hospital	Capelle Aan Den IJssel	Zuid-Holland
Netherlands	Haga Hospital	Den Haag	Zuid-Holland
Netherlands	Deventer Hospital	Deventer	Overijssel
Netherlands	Albert Schweitzer Hospital	Dordrecht	Zuid-Holland
Netherlands	Nij Smellinghe Hospital	Drachten	Friesland
Netherlands	Hospital Gelderse Vallei	Ede	Gelderland
Netherlands	Catharina Hospital	Eindhoven	Noord-Brabant
Netherlands	Rivas Zorggroep	Gorinchem	Zuid-Holland
Netherlands	Groene Hart Hospital	Gouda	Zuid-Holland
Netherlands	Martini Hospital	Groningen
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Spaarne Gasthuis	Haarlem	Noord-Holland
Netherlands	Ziekenhuis Groep Twente	Hengelo	Overijssel
Netherlands	Alrijne Hospital	Leiden	Zuid-Holland
Netherlands	Maastricht University Medical Center	Maastricht	Limburg
Netherlands	Sint Antonius Hospital	Nieuwegein	Utrecht
Netherlands	Canisius Wilhelmina Hospital	Nijmegen	Gelderland
Netherlands	Radboud University Medical Center	Nijmegen	Gelderland
Netherlands	Erasmus Medical Center, Gastroenterology department	Rotterdam	Zuid-Holland
Netherlands	Franciscus Gasthuis	Rotterdam	Zuid-Holland
Netherlands	Ikazia Hospital	Rotterdam	Zuid-Holland
Netherlands	Maasstad Hospital	Rotterdam	Zuid-Holland
Netherlands	Vlietland Hospital	Schiedam	Zuid-Holland
Netherlands	Antonius Hospital Sneek-Emmeloord	Sneek	Friesland
Netherlands	Bernhoven	Uden	Noord-Brabant
Netherlands	University Medical Center Utrecht, Gastroenterology department	Utrecht
Netherlands	Isala Clinics	Zwolle	Overijssel

Sponsors (5)

Lead Sponsor	Collaborator
Dr. Frank ter Borg MD PhD	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Erasmus Medical Center, The Netherlands Cancer Institute, UMC Utrecht

Country where clinical trial is conducted

Netherlands, 

References & Publications (11)

Benizri EI, Bereder JM, Rahili A, Bernard JL, Vanbiervliet G, Filippi J, Hébuterne X, Benchimol D. Additional colectomy after colonoscopic polypectomy for T1 colon cancer: a fine balance between oncologic benefit and operative risk. Int J Colorectal Dis. 2012 Nov;27(11):1473-8. doi: 10.1007/s00384-012-1464-0. Epub 2012 Mar 29. — View Citation

Butte JM, Tang P, Gonen M, Shia J, Schattner M, Nash GM, Temple LK, Weiser MR. Rate of residual disease after complete endoscopic resection of malignant colonic polyp. Dis Colon Rectum. 2012 Feb;55(2):122-7. doi: 10.1097/DCR.0b013e3182336c38. Erratum in: Dis Colon Rectum. 2012 Apr;55(4):498. Nash, Garret M [corrected to Nash, Garrett M]. — View Citation

Cooper GS, Xu F, Barnholtz Sloan JS, Koroukian SM, Schluchter MD. Management of malignant colonic polyps: a population-based analysis of colonoscopic polypectomy versus surgery. Cancer. 2012 Feb 1;118(3):651-9. doi: 10.1002/cncr.26340. Epub 2011 Jul 12. — View Citation

Di Gregorio C, Bonetti LR, de Gaetani C, Pedroni M, Kaleci S, Ponz de Leon M. Clinical outcome of low- and high-risk malignant colorectal polyps: results of a population-based study and meta-analysis of the available literature. Intern Emerg Med. 2014 Mar;9(2):151-60. doi: 10.1007/s11739-012-0772-2. Epub 2012 Mar 27. Review. — View Citation

Ikematsu H, Yoda Y, Matsuda T, Yamaguchi Y, Hotta K, Kobayashi N, Fujii T, Oono Y, Sakamoto T, Nakajima T, Takao M, Shinohara T, Murakami Y, Fujimori T, Kaneko K, Saito Y. Long-term outcomes after resection for submucosal invasive colorectal cancers. Gastroenterology. 2013 Mar;144(3):551-9; quiz e14. doi: 10.1053/j.gastro.2012.12.003. Epub 2012 Dec 8. — View Citation

Kitajima K, Fujimori T, Fujii S, Takeda J, Ohkura Y, Kawamata H, Kumamoto T, Ishiguro S, Kato Y, Shimoda T, Iwashita A, Ajioka Y, Watanabe H, Watanabe T, Muto T, Nagasako K. Correlations between lymph node metastasis and depth of submucosal invasion in submucosal invasive colorectal carcinoma: a Japanese collaborative study. J Gastroenterol. 2004 Jun;39(6):534-43. — View Citation

Meining A, von Delius S, Eames TM, Popp B, Seib HJ, Schmitt W. Risk factors for unfavorable outcomes after endoscopic removal of submucosal invasive colorectal tumors. Clin Gastroenterol Hepatol. 2011 Jul;9(7):590-4. doi: 10.1016/j.cgh.2011.02.002. Epub 2011 Feb 12. — View Citation

Mitchell PJ, Haboubi NY. The malignant adenoma: when to operate and when to watch. Surg Endosc. 2008 Jul;22(7):1563-9. doi: 10.1007/s00464-008-9850-y. Epub 2008 Mar 25. Review. — View Citation

Netzer P, Forster C, Biral R, Ruchti C, Neuweiler J, Stauffer E, Schönegg R, Maurer C, Hüsler J, Halter F, Schmassmann A. Risk factor assessment of endoscopically removed malignant colorectal polyps. Gut. 1998 Nov;43(5):669-74. — View Citation

Seitz U, Bohnacker S, Seewald S, Thonke F, Brand B, Bräiutigam T, Soehendra N. Is endoscopic polypectomy an adequate therapy for malignant colorectal adenomas? Presentation of 114 patients and review of the literature. Dis Colon Rectum. 2004 Nov;47(11):1789-96; discussion 1796-7. Review. — View Citation

Ueno H, Mochizuki H, Hashiguchi Y, Shimazaki H, Aida S, Hase K, Matsukuma S, Kanai T, Kurihara H, Ozawa K, Yoshimura K, Bekku S. Risk factors for an adverse outcome in early invasive colorectal carcinoma. Gastroenterology. 2004 Aug;127(2):385-94. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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