Molecular Stool Testing for Colorectal Cancer Surveillance

Completed

• Conditions: Colorectal Cancer

• Registration Number: NCT02715141
• Lead Sponsor: The Netherlands Cancer Institute

Brief Summary

Rationale: Since January 2014 the Dutch screening programme for bowel cancer has been implemented. Screening will increase the demand for surveillance. Although patients in whom adenomas have been removed are at increased risk of progressing to cancer, solid evidence on the reduction of death from CRC through the current colonoscopy-based surveillance is lacking. Furthermore, colonoscopy-based surveillance leads to high logistic demands, high individual burden and high costs. Therefore, there is need for new surveillance strategies. Stool-based molecular testing (Cologuard®, consisting of a stool DNA test and an immunochemical assay for human hemoglobin) or Faecal Immunochemical Testing (FIT) may serve as an alternative for colonoscopy surveillance.

The aim of this study is to compare the accuracy of an established molecular stool test (Cologuard®) and FIT to colonoscopy for detection of advanced adenomas or CRC (advanced neoplasia) in a surveillance population. These outcomes will be used to model various strategies of stool-based molecular surveillance to inform health policy decisions.

Detailed Description

BACKGROUND: Since January 2014 the Dutch screening programme for colorectal carcinoma (CRC) has been implemented. Screening will increase the demand for surveillance. However, solid evidence on the reduction of death from CRC through the current colonoscopy-based surveillance is lacking. Furthermore, colonoscopy-based surveillance leads to high logistic demands, high patient burden and high costs. Therefore, there is need for new surveillance strategies. Stool-based molecular testing (Cologuard®) or Faecal Immunochemical Testing (FIT) may serve as an alternative for colonoscopy surveillance.

OBJECTIVES:

1. To compare the accuracy of an established molecular stool test (Cologuard®) and FIT to colonoscopy for detection of advanced adenomas or CRC (advanced neoplasia) in a surveillance population.

2. To model various strategies of stool-based molecular surveillance to inform health policy decisions.

MATERIALS AND METHODS: In this prospective observational cross-sectional cohort study, individuals aged 50-75 years that are scheduled for surveillance colonoscopy will be invited to participate. They are asked to collect a whole-stool sample prior to the surveillance colonoscopy. The sample will be used to test for the presence of molecular stool markers. The results of the molecular stool test and FIT will be compared to the colonoscopy findings.

EXPECTED RESULTS: Frequent surveillance using stool-based molecular testing is more cost-effective than the current colonoscopy-based surveillance.

Study Timeline

• Study Start: 2015-10
• Study First Submitted: 2016-02-17
• Study First Submitted QC: 2016-03-16
• Study First Posted: 2016-03-22
• Primary Completion: 2020-12
• Study Completion: 2020-12-15
• Status Verified: 2022-01
• Last Update Submitted: 2022-01-24
• Last Update Posted: 2022-01-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 3966

Inclusion Criteria

• Subjects in the age group 50-75 years. The lower age limit is set at 50 years because of the high probability of familiar predisposition when advanced neoplasm is present in a younger age group.26 The upper age limit of 75 years is in correspondence with the recommended stop-age for surveillance according to the current guideline.9
• Subjects with an indication for surveillance colonoscopy according to the previous guideline ('Follow up after polypectomy', 2002; summarized in 2008) or current ('Colonoscopy Surveillance', 2013) guideline. This includes subjects with a history of CRC or polypectomy, as well as subjects under surveillance for familial colorectal carcinoma (FCC).
• Subjects who have sufficient comprehension of the Dutch language.
• Subjects who have given their informed consent.

Exclusion criteria:

• Subjects with inflammatory bowel disease (IBD)
• Subjects with Lynch syndrome, familial adenomatous polyposis (FAP), attenuated FAP (AFAP), MUTYH associated polyposis (MAP) and serrated polyposis syndrome (SPS)
• Subjects with a previous colonoscopy < 6 months (rescopy)
• Subjects with proctocolectomy
• Subjects with life expectancy < 3 years

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
accuracy of molecular stool test (Cologuard) and FIT	Patient inclusion for the calculation of the accuracies is expected to take 2-3 years.	The accuracy (sensitivity, specificity, PPV and NPV) of the molecular stool test (Cologuard®) and FIT compared to colonoscopy in the detection of advanced neoplasia in a surveillance population.
cost-effectiveness of stool-based surveillance strategies using the ASCCA (Adenoma and Serrated pathway to Colorectal CAncer) model	This will be calculated when all accuracy data (outcome 1) are available. This is expected to be 6 months after end of study.	Cost-effectiveness of multiple surveillance strategies, using test performance data as input in the ASCCA (Adenoma and Serrated pathway to Colorectal CAncer) model.
life time health effects of stool-based surveillance strategies using the ASCCA (Adenoma and Serrated pathway to Colorectal CAncer) model	This will be calculated when all accuracy data (outcome 1) are available. This is expected to be 6 months after end of study.	The ASCCA model will be used to predict outcomes, including cancer incidence and mortality, for different surveillance strategies.

Secondary Outcome Measures

Name	Time	Method
presence of previously identified progression biomarker on resected tissue samples of polyps	Analysis will be performed during the study and approximately 1 year after end of study	The identification of biomarkers involved in the progression from colorectal adenoma to carcinoma (progression biomarkers) could aid better risk-stratification of adenomas and thereby decrease over-diagnosis and over-treatment . As a secondary objective we will therefore analyse previously identified progression biomarkers in the tissue samples of polyps obtained during colonoscopy.
risk of CRC	up to one month after surveillance colonoscopy	Risk factors for detecting advanced colonic neoplasia have been identified, of which the most established include gender, age, BMI, family history, physical activity, nutritional habits and smoking. Participants will be asked to complete a validated online questionnaire evaluating these risk factors.
presence of Cologuard marker pannel on resected tissue of polyps	Analysis will be performed during the study and approximately 1 year after end of study	A challenge associated with the use of molecular markers is to find a panel of markers that represents the heterogeneity of the tumour. Therefore it is of interest to analyse whether the markers included in the Cologuard are present in the tissue of resected polyps.

Trial Locations

Locations (1)

Nethelands Cancer Institute; 🇳🇱 Amsterdam, Noord-Holland, Netherlands