SCar-biopsies After Malignant Colorectal Polypectomy of Uncertain RAdicality (SCAPURA)

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

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.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer
• Intervention / Treatment: Procedure: Flexible sigmoidoscopy or colonoscopy

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 246
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9700 RB
    • University Medical Center Groningen
  • Groningen, Netherlands, 9728NT
    • Martini Hospital
  • Utrecht, Netherlands, 3508 GA
    • University Medical Center Utrecht, Gastroenterology department
  • Friesland
    • Drachten, Friesland, Netherlands, 9202NN
      • Nij Smellinghe hospital
    • Sneek, Friesland, Netherlands, 8601ZK
      • Antonius Hospital Sneek-Emmeloord
  • Gelderland
    • Apeldoorn, Gelderland, Netherlands, 7332BP
      • Medical Center de Veluwe
    • Apeldoorn, Gelderland, Netherlands, 7334
      • Gelre Hospitals
    • Ede, Gelderland, Netherlands, 6716RP
      • Hospital Gelderse Vallei
    • Nijmegen, Gelderland, Netherlands, 6532SZ
      • Canisius Wilhelmina Hospital
    • Nijmegen, Gelderland, Netherlands, 6525GA
      • Radboud University Medical Center
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229
      • Maastricht University Medical Center
  • Noord-Brabant
    • Beugen, Noord-Brabant, Netherlands, 5835DV
      • Maasstad Hospital Pantein
    • Breda, Noord-Brabant, Netherlands, 4819EV
      • Amphia Hospital
    • Eindhoven, Noord-Brabant, Netherlands, 5623EJ
      • Catharina Hospital
    • Uden, Noord-Brabant, Netherlands, 5406PT
      • Bernhoven
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1066 CX
      • The Netherlands Cancer Institute Antoni van Leeuwenhoekhuis
    • Amsterdam, Noord-Holland, Netherlands, 1066EC
      • Medical Center Slotervaart
    • Amsterdam, Noord-Holland, Netherlands, 1091AC
      • Onze Lieve Vrouwe Gasthuis (Oost & West)
    • Amsterdam, Noord-Holland, Netherlands, 1105 AZ
      • Academical Medical Center, Gastroenterology department
    • Haarlem, Noord-Holland, Netherlands, 2035RC
      • Spaarne Gasthuis
  • Overijssel
    • Deventer, Overijssel, Netherlands, 7416 SE
      • Deventer Hospital
    • Hengelo, Overijssel, Netherlands, 7555DL
      • Ziekenhuis Groep Twente
    • Zwolle, Overijssel, Netherlands, 8025AB
      • Isala Clinics
  • Utrecht
    • Amersfoort, Utrecht, Netherlands, 3813TZ
      • Meander Medical Center
    • Nieuwegein, Utrecht, Netherlands, 3435CM
      • Sint Antonius Hospital
  • Zuid-Holland
    • Capelle Aan Den IJssel, Zuid-Holland, Netherlands, 2906ZC
      • Ijsselland Hospital
    • Den Haag, Zuid-Holland, Netherlands, 2545AA
      • Haga hospital
    • Dordrecht, Zuid-Holland, Netherlands, 3318AT
      • Albert Schweitzer Hospital
    • Gorinchem, Zuid-Holland, Netherlands, 4206CC
      • Rivas Zorggroep
    • Gouda, Zuid-Holland, Netherlands, 2803HH
      • Groene Hart Hospital
    • Leiden, Zuid-Holland, Netherlands, 2334CK
      • Alrijne Hospital
    • Rotterdam, Zuid-Holland, Netherlands, 3015 CE
      • Erasmus Medical Center, Gastroenterology department
    • Rotterdam, Zuid-Holland, Netherlands, 3045PM
      • Franciscus Gasthuis
    • Rotterdam, Zuid-Holland, Netherlands, 3079DZ
      • Maasstad Hospital
    • Rotterdam, Zuid-Holland, Netherlands, 3083AN
      • Ikazia Hospital
    • Schiedam, Zuid-Holland, Netherlands, 3118JH
      • Vlietland Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Flexible sigmoidoscopy or colonoscopy; Subjects will undergo these investigation to take biopsies from the polypectomy scar.	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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Dr. Frank ter Borg MD PhD
• Collaborators: UMC Utrecht; Erasmus Medical Center; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); The Netherlands Cancer Institute
• Investigators: Study Director: Frank ter Borg, MD PhD, Department of Gastroenterology & Hematology, Deventer Hospital

Publications and helpful links

General Publications

• 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.
• Seitz U, Bohnacker S, Seewald S, Thonke F, Brand B, Braiutigam 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. doi: 10.1007/s10350-004-0680-2.
• 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].
• 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.
• Benizri EI, Bereder JM, Rahili A, Bernard JL, Vanbiervliet G, Filippi J, Hebuterne 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.
• 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.
• 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. doi: 10.1007/s00535-004-1339-4.
• 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. doi: 10.1053/j.gastro.2004.04.022.
• Netzer P, Forster C, Biral R, Ruchti C, Neuweiler J, Stauffer E, Schonegg R, Maurer C, Husler J, Halter F, Schmassmann A. Risk factor assessment of endoscopically removed malignant colorectal polyps. Gut. 1998 Nov;43(5):669-74. doi: 10.1136/gut.43.5.669.
• 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.
• 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.
• Gijsbers KM, Post Z, Schrauwen RWM, Tang TJ, Bisseling TM, Bac DJ, Veenstra RP, Schreuder RM, Epping Stippel LSM, de Vos Tot Nederveen Cappel WH, Slangen RME, van Lelyveld N, Witteman EM, van Milligen de Wit MAWM, Honkoop P, Alderlieste Y, Ter Borg PJC, van Roermund R, Schmittgens S, Dekker E, Leeuwenburgh I, de Ridder RJJ, Zonneveld AM, Hadithi M, van Leerdam ME, Bruno MJ, Vleggaar FP, Moons LMG, Koch AD, Ter Borg F. Low value of second-look endoscopy for detecting residual colorectal cancer after endoscopic removal. Gastrointest Endosc. 2020 Jul;92(1):166-172. doi: 10.1016/j.gie.2020.01.056. Epub 2020 Feb 25.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Actual): May 1, 2019
• Study Completion (Actual): May 1, 2019

Study Registration Dates

• First Submitted: December 15, 2014
• First Submitted That Met QC Criteria: December 29, 2014
• First Posted (Estimate): December 31, 2014

Study Record Updates

• Last Update Posted (Actual): December 17, 2019
• Last Update Submitted That Met QC Criteria: December 13, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Endoscopic resection; Pathology; Rescue surgery
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: SCAPURA-Study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Data collection is within current OpenClinica standard and not shared