MOlecular stool testing for Colorectal CAncer Surveillance

With more than 13.000 new patients and >5.000 deaths per year in the
Netherlands, colorectal cancer (CRC) poses a big health problem. Screening for
early stage, treatable tumours is a cost-effective approach to tackle this
problem. Therefore, population-wide CRC screening was implemented in the
Netherlands in 2014, using the Faecal Immunochemical Test (FIT). About 6% of
screenees will test positive, yielding approximately 80.000 extra colonoscopies
per year. Of these screenees >40% will have (advanced) adenomas and most of
them will qualify for surveillance colonoscopies according to the current
guideline.

While post-polypectomy surveillance consumes about 25% of colonoscopy capacity,
experts agree that evidence for the impact of colonoscopic post-polypectomy
surveillance on the ultimate endpoint, i.e. death from CRC, is limited and
current surveillance strategies lead to overdiagnosis and over-treatment. The
revised Dutch surveillance guideline (2013), although more risk-based than the
previous guidelines and than international guidelines, will not be able to
solve this. Besides the overuse, colonoscopy is an invasive procedure with a
burden and also a risk for complications. Therefore there is a need for
alternative, preferably non-invasive, surveillance tests.

Stool-based molecular testing may well be an alternative for colonoscopy
surveillance as molecular tests are more specific than colonoscopy for relevant
adenomas and less burdensome for patients. While the sensitivity of a single
molecular test for the detection of cancers and advanced adenomas is lower than
that of colonoscopy, an approach of repeated molecular tests (e.g. biennially)
may yield similar detection rates as a colonoscopy based surveillance
programme. If validated for this purpose, stool-based molecular surveillance
tests has the potential to dramatically decrease the demand for colonoscopy
capacity.

1. To determine the accuracy (i.e. sensitivity, specificity, PPV and NPV) of:
a. A molecular stool test, i.e. Cologuard® (Exact Sciences, Madison, WI, USA)
consisting of a stool DNA test and an immunochemical assay for human hemoglobin;
b. FIT: OC-sensor® (Eiken Chemical Co., Tokyo, Japan) and FOB GoldTM (Sentinel,
Milan, Italy);
in the detection of advanced neoplasia compared to colonoscopy in a
surveillance population.

2. To model various strategies of surveillance based on colonoscopy or
alternative surveillance tools using the obtained accuracy data from the
molecular stool test (Cologuard®) and FIT.

The current project is designed as a prospective observational cross-sectional
cohort study.

Through this design, rates of advanced neoplasia as detected by the molecular
stool test (Cologuard®) and FIT will be compared to the results as detected by
colonoscopy. Colonoscopy in combination with histology is considered the gold
standard for the diagnosis of advanced neoplasia. All subjects scheduled for
(elective) colonoscopy surveillance in the participating centres (i.e. AMC,
Antoni van Leeuwenhoek Hospital, Slotervaart Hospital, MUMC, Kennemer Gasthuis
Haarlem and Flevoziekenhuis Almere) who are eligible for this study according
to the in- and exclusion criteria, will be invited to participate. Necessary
faeces collection is scheduled at home just before the surveillance colonoscopy
and before bowel preparation. Participants receive a questionnaire before the
scheduled colonoscopy to assess risk-factors for CRC.

Burden for participant consists of at home faeces collection and the completion
of a questionnaire.