Clinical trial NCT02715141: Molecular Stool Testing for Colorectal Cancer Surveillance
Official title: Molecular Stool Testing for Colorectal Cancer Surveillance
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Colorectal Cancer
Keywords: surveillance, molecular stool testing
Lead sponsor: The Netherlands Cancer Institute
Sponsor class: OTHER
Collaborators: name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Maastricht University Medical Center
First posted: 2016-03-22
Enrollment: 3966
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The intended population of this study consists all subjects in the participating centres that are elected for colonoscopy surveillance.

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.

Eligibility criteria: 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

Primary outcomes:
measure: accuracy of molecular stool test (Cologuard) and FIT
timeFrame: Patient inclusion for the calculation of the accuracies is expected to take 2-3 years.
measure: cost-effectiveness of stool-based surveillance strategies using the ASCCA (Adenoma and Serrated pathway to Colorectal CAncer) model
timeFrame: This will be calculated when all accuracy data (outcome 1) are available. This is expected to be 6 months after end of study.
measure: life time health effects of stool-based surveillance strategies using the ASCCA (Adenoma and Serrated pathway to Colorectal CAncer) model
timeFrame: This will be calculated when all accuracy data (outcome 1) are available. This is expected to be 6 months after end of study.
Secondary outcomes:
measure: risk of CRC
timeFrame: up to one month after surveillance colonoscopy
measure: presence of Cologuard marker pannel on resected tissue of polyps
timeFrame: Analysis will be performed during the study and approximately 1 year after end of study
measure: presence of previously identified progression biomarker on resected tissue samples of polyps
timeFrame: Analysis will be performed during the study and approximately 1 year after end of study
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Nethelands Cancer Institute
state: Noord-Holland
Study officials:
References:
citation: van Lanschot MC, Carvalho B, Coupe VM, van Engeland M, Dekker E, Meijer GA. Molecular stool testing as an alternative for surveillance colonoscopy: a cross-sectional cohort study. BMC Cancer. 2017 Feb 7;17(1):116. doi: 10.1186/s12885-017-3078-y.