ESD for Colorectal LSL Using a Selective Strategy - a Prospective Cohort Study

Colorectal Neoplasm Clinical Trial

— COVERT  

Official title:

Endoscopic Submucosal Dissection for Sessile Polyps and Laterally Spreading Lesions of the Colorectum Using a Selective Strategy - a Prospective Cohort Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04008407
• Other study ID #: AU RED HREC/17/WMEAD/497
• Status: Recruiting
• Phase: N/A
• Start date: August 14, 2017
• Est. completion date: February 2028

Study information

• Verified date: June 2023
• Source: Western Sydney Local Health District
• Contact: Michael J Bourke, Prof.
• Phone: +61288905555
• Email: endoscopyresearch.westmead[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Colonic Laterally spreading lesions (LSL) => 20mm are at high risk to progress to cancer. Overt stigmata of submucosal invasive cancer (SMIC) has been well characterized and includes ulceration and surface pit pattern changes as per the Kudo classification of type V.

In a recent report, risk factors for LSL with SMIC and no overt stigmata (i.e. covert SMIC) were described. Resection of these lesions 'en-bloc' can allow for better histological staging and potentially reduce the need for surgical resection.

Description:

With over 14,000 patients diagnosed annually, colorectal carcinoma (CRC) is the second most frequently invasive malignancy in Australia. By not only diagnosing CRC at an early stage, but also removing precursor adenomas, colonoscopy with polypectomy reduces the risk of developing and dying from CRC.

Laterally spreading lesions >= 20mm (LSL) are more likely to progress to cancer. The prevalence of LSL ranges from 1-5% in screening population. The risk of malignant progression of colorectal adenomas found during colonoscopy increases with lesion size, i.e. the cancer preventive effect is likely to be maximal in large lesions. Patients with LSL have a higher risk of malignancy and a higher recurrence rate of adenoma after lesion removal compared with diminutive polyps.

Endoscopic imaging can now accurately predict LSL with submucosal invasive cancer (SMIC) through assessment of LSLs morphology (Paris classification, granularity) and surface pit-pattern (Kudo classification). Such cases can be considered to have LSL with overt risk of SMIC.

Recent publication has highlighted that some LSLs might hrbor SMIC without overt morphological features (i.e. high risk for covert SMIC). These LSL with high risk of covert SMIC stratified LSLs based on lesion location and lesion morphology.

Generally LSLs can be safely and effectively removed by wide field endoscopic mucosal resection (WF-EMR) in over 90% of cases in competent hands.

One of the draw backs with WF-EMR is it requires piecemeal resection and thus is limited in providing assessment of complete excision and depth of submucosal invasion in cases where SMIC is present.

Thus, endoscopic en-bloc resection is preferable from an oncologic standpoint to obtain a single specimen for proper histopathologic assessment. Endoscopic submucosal dissection (ESD) is a technique that is now becoming the preferred method for achieving a complete endoscopic and histologic resection, referred to as R0. Evidence from retrospective cohort and meta-analyses suggests ESD provides a more consistent oncologic resection with a reduced rate of recurrence. However, the major limitations with the technique relate to increased procedure time and the skill-set required for performing the procedure.

One of the other major limitations of ESD is significant cost associated with the procedure, which includes procedure time and additional equipment in addition to the treatment of any subsequent complications. As such the implementation of ESD as the standard of care for all colorectal lesions has not been undertaken in Western countries, however it may have an important role for selective cases especially where there is concern for sub-mucosal invasive cancer (SMIC).

The investigators propose a selective ESD strategy to be performed for patients focusing on overt evidence of SMIC and those at high risk of covert SMIC (defined as risk >10%). The investigators will follow a prospective cohort study assessing the use of selective ESD strategy in the colorectum in the Western population.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 391
• Est. completion date: February 2028
• Est. primary completion date: August 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• All patients referred for colorectal resection of large laterally spreading lesions in colon.

• Can give informed consent to trial participation

Exclusion Criteria:

• Previous resection or attempted resection of target adenoma lesion

• Endoscopic appearance of invasive malignancy

• Age less than 18 years

• Pregnancy

• Active Inflammatory colonic conditions (e.g. inflammatory bowel disease)

• Use of anticoagulant or antiplatelet agents other than aspirin outside of internationally recognised guidelines

• American Society of Anesthesiology (ASA) Grade IV-V

Related Conditions & MeSH terms

• Colorectal Neoplasm
• Colorectal Neoplasms
• Endoscopic Mucosal Resection

Intervention

Procedure:
• Endoscopic Submucosal Dissection
Endoscopic Submucosal Dissection (ESD) results in en-bloc resection of LSL, regardless of lesion size. This allows for accurate histopathological assessment of SMIC, R0/R1 resection and depth of invasion. ESD is considered a potentially curative for superficial cancers (T1a).
• Endoscopic Mucosal Resection
EMR is the current standard for treating colonic LSL and has been validated to be safe and efficacious. LSLs => 20mm are frequently resected piecemeal. Recent research show that resection margin soft coagulation reduces recurrence rates to those similar to en-bloc resections.

Locations

Country	Name	City	State
Australia	Westmead Endoscopy Unit	Westmead	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
Western Sydney Local Health District

Country where clinical trial is conducted

Australia, 

References & Publications (10)

Burgess NG, Hourigan LF, Zanati SA, Brown GJ, Singh R, Williams SJ, Raftopoulos SC, Ormonde D, Moss A, Byth K, Mahajan H, McLeod D, Bourke MJ. Risk Stratification for Covert Invasive Cancer Among Patients Referred for Colonic Endoscopic Mucosal Resection: — View Citation

Iishi H, Tatsuta M, Iseki K, Narahara H, Uedo N, Sakai N, Ishikawa H, Otani T, Ishiguro S. Endoscopic piecemeal resection with submucosal saline injection of large sessile colorectal polyps. Gastrointest Endosc. 2000 Jun;51(6):697-700. doi: 10.1067/mge.20 — View Citation

Lee EJ, Lee JB, Lee SH, Youk EG. Endoscopic treatment of large colorectal tumors: comparison of endoscopic mucosal resection, endoscopic mucosal resection-precutting, and endoscopic submucosal dissection. Surg Endosc. 2012 Aug;26(8):2220-30. doi: 10.1007/ — View Citation

Moss A, Bourke MJ, Williams SJ, Hourigan LF, Brown G, Tam W, Singh R, Zanati S, Chen RY, Byth K. Endoscopic mucosal resection outcomes and prediction of submucosal cancer from advanced colonic mucosal neoplasia. Gastroenterology. 2011 Jun;140(7):1909-18. — View Citation

Nanda KS, Tutticci N, Burgess NG, Sonson R, Williams SJ, Bourke MJ. Endoscopic mucosal resection of laterally spreading lesions involving the ileocecal valve: technique, risk factors for failure, and outcomes. Endoscopy. 2015 Aug;47(8):710-8. doi: 10.1055 — View Citation

Oka S, Tanaka S, Saito Y, Iishi H, Kudo SE, Ikematsu H, Igarashi M, Saitoh Y, Inoue Y, Kobayashi K, Hisabe T, Tsuruta O, Sano Y, Yamano H, Shimizu S, Yahagi N, Watanabe T, Nakamura H, Fujii T, Ishikawa H, Sugihara K; Colorectal Endoscopic Resection Standa — View Citation

Risio M. The natural history of colorectal adenomas and early cancer. Pathologe. 2012 Nov;33 Suppl 2:206-10. doi: 10.1007/s00292-012-1640-6. — View Citation

Terasaki M, Tanaka S, Oka S, Nakadoi K, Takata S, Kanao H, Yoshida S, Chayama K. Clinical outcomes of endoscopic submucosal dissection and endoscopic mucosal resection for laterally spreading tumors larger than 20 mm. J Gastroenterol Hepatol. 2012 Apr;27( — View Citation

Winawer SJ, Zauber AG, Ho MN, O'Brien MJ, Gottlieb LS, Sternberg SS, Waye JD, Schapiro M, Bond JH, Panish JF, et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med. 1993 Dec 30;329(27):1977-81 — View Citation

Zauber AG, Winawer SJ, O'Brien MJ, Lansdorp-Vogelaar I, van Ballegooijen M, Hankey BF, Shi W, Bond JH, Schapiro M, Panish JF, Stewart ET, Waye JD. Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. N Engl J Med. 2012 Feb 23;366 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of surgical referral	Incidence of surgical referral due to non-curative endoscopic resection.	3 months post procedure
Secondary	R0 resection rate	Rate of en-bloc resection with clear resection margins.	3 months post procedure
Secondary	En Bloc resection rate	Rate of en-bloc resection	3 months post procedure
Secondary	Technical success rate	Rate of procedures completed as per protocol	3 months post procedure
Secondary	Duration of procedure	Procedure duration in minutes.	procedure
Secondary	Adenoma recurrence rate	Rate of recurrent adenoma at resection site on follow-up.	3 years post procedure