Clinical trial NCT02328664: SCar-biopsies After Malignant Colorectal Polypectomy of Uncertain RAdicality
Official title: The Sensitivity of Scar-biopsies for Residual Colorectal Adenocarcinoma After Endoscopic Resection With Uncertain Radicality
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Colorectal Cancer
Keywords: Endoscopic resection
Pathology
Rescue surgery
Lead sponsor: Deventer Ziekenhuis
Sponsor class: OTHER
Collaborators: name: Erasmus Medical Center
name: The Netherlands Cancer Institute
name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: UMC Utrecht
First posted: 2014-12-31
Enrollment: 246
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Sensitivity of biopsies for residual cancer
timeFrame: up to 1 year
Secondary outcomes:
measure: 90-day mortality after rescue surgery
timeFrame: 91 days from surgery
measure: The sensitivity of biopsies for residual cancer in the bowel wall
timeFrame: up to 1 year
measure: The number of complications (defined according to GCP) after biopsies from the polypectomy scar
timeFrame: up to 30 days
measure: The sensitivity of global endoscopic assessment of polypectomy site for residual cancer at initial and follow-up endoscopy (to take scar biopsies)
timeFrame: up to 1 year
measure: The proportion of patients with residual cancer in the resected specimen if malignancy was unsuspected during the endoscopic polypectomy
timeFrame: up to 1 year
Other outcomes:
Locations:
city: Drachten
country: Netherlands
facility: Nij Smellinghe Hospital
state: Friesland
city: Sneek
country: Netherlands
facility: Antonius Hospital Sneek-Emmeloord
state: Friesland
city: Apeldoorn
country: Netherlands
facility: Medical Center de Veluwe
state: Gelderland
city: Apeldoorn
country: Netherlands
facility: Gelre Hospitals
state: Gelderland
city: Ede
country: Netherlands
facility: Hospital Gelderse Vallei
state: Gelderland
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
state: Gelderland
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Hospital
state: Gelderland
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
state: Limburg
city: Beugen
country: Netherlands
facility: Maasstad Hospital Pantein
state: Noord-Brabant
city: Breda
country: Netherlands
facility: Amphia Hospital
state: Noord-Brabant
city: Eindhoven
country: Netherlands
facility: Catharina Hospital
state: Noord-Brabant
city: Uden
country: Netherlands
facility: Bernhoven
state: Noord-Brabant
city: Amsterdam
country: Netherlands
facility: The Netherlands Cancer Institute Antoni van Leeuwenhoekhuis
state: Noord-Holland
city: Amsterdam
country: Netherlands
facility: Medical Center Slotervaart
state: Noord-Holland
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis (Oost & West)
state: Noord-Holland
city: Amsterdam
country: Netherlands
facility: Academical Medical Center, Gastroenterology department
state: Noord-Holland
city: Haarlem
country: Netherlands
facility: Spaarne Gasthuis
state: Noord-Holland
city: Deventer
country: Netherlands
facility: Deventer Hospital
state: Overijssel
city: Hengelo
country: Netherlands
facility: Ziekenhuis Groep Twente
state: Overijssel
city: Zwolle
country: Netherlands
facility: Isala Clinics
state: Overijssel
city: Amersfoort
country: Netherlands
facility: Meander Medical Center
state: Utrecht
city: Nieuwegein
country: Netherlands
facility: Sint Antonius Hospital
state: Utrecht
city: Capelle Aan Den IJssel
country: Netherlands
facility: IJsselland Hospital
state: Zuid-Holland
city: Den Haag
country: Netherlands
facility: Haga Hospital
state: Zuid-Holland
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Hospital
state: Zuid-Holland
city: Gorinchem
country: Netherlands
facility: Rivas Zorggroep
state: Zuid-Holland
city: Gouda
country: Netherlands
facility: Groene Hart Hospital
state: Zuid-Holland
city: Leiden
country: Netherlands
facility: Alrijne Hospital
state: Zuid-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center, Gastroenterology department
state: Zuid-Holland
city: Rotterdam
country: Netherlands
facility: Franciscus Gasthuis
state: Zuid-Holland
city: Rotterdam
country: Netherlands
facility: Maasstad Hospital
state: Zuid-Holland
city: Rotterdam
country: Netherlands
facility: Ikazia Hospital
state: Zuid-Holland
city: Schiedam
country: Netherlands
facility: Vlietland Hospital
state: Zuid-Holland
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Groningen
country: Netherlands
facility: Martini Hospital
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht, Gastroenterology department
Study officials:
affiliation: Department of Gastroenterology & Hematology, Deventer Hospital
name: Frank ter Borg, MD PhD
role: STUDY_DIRECTOR
References:
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.
citation: 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.
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.
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.
citation: 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.
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.
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. doi: 10.1007/s00535-004-1339-4.
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. doi: 10.1053/j.gastro.2004.04.022.
citation: 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.
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.
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.
citation: 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.