The Diverticulitis Study - Circulating tumor DNA guided vs opportunistic colonoscopy screening for CRC detection after acute colonic diverticulitis
Acute colonic diverticulitis is inflammation of the colonic diverticulum, and this common disease are confirmed by an abdominal CT scan. For patients who have experienced an episode of acute colonic diverticulitis, Danish and international guidelines recommend opportunistic screening with colonoscopy to rule out CRC as the underlying reason for the diverticulitis symptoms. In Denmark there are >4000 hospitalizations/year. Thus, an unreasonably high number of colonoscopies, ranging from 50 and up to >200, are needed to diagnose 1 CRC. In comparison, a >4% CRC prevalence is considered the minimal acceptable among patients selected for follow-up colonoscopy in the Danish nation-wide CRC screening program, corresponding to <25 colonoscopies per CRC. Hence, it may be questioned whether the current guidelines on follow-up colonoscopy after diverticulitis are at all acceptable, both from a patient perspective and from a health-economy perspective. However, it has been very difficult to change. Consequently, there is an urgent need for a highly sensitive, low risk, minimal invasive cancer detection test that can be used to triage newly diagnosed diverticulitis patients, and ensure that underlying CRC is still diagnosed, but minimizing the number of patients needing colonoscopy. Here, we propose to conduct a prospective observational case/control study to explore the feasibility of using our recently developed TriMeth ctDNA analysis test for this purpose.
We will enrol a minimum of 220 newly diagnosed diverticulitis patients eligible to opportunistic CRC colonoscopy screening in accordance with the Danish guideline. The patients will be recruited in four Danish regions. Prior to the standard-of-care colonoscopy, a blood sample will be collected and tested for ctDNA using TriMeth. The colonoscopy findings will be registered and used to divide the patients into cases (CRC identified) and controls (no CRC identified). The pre-colonoscopy ctDNA status will be compared to the colonoscopy status to assess the potential benefit of triaging the diverticulitis patients with ctDNA analysis.
Finally, we will conduct a health-economy assessment comparing the TriMeth guided approach to the current practice of ‘colonoscopy for all’.
We expect the study to document that ctDNA triaging, will: 1) improve quality of life for diverticulitis patients with no underlying CRC, 2) be cost-effective, as many unnecessary diagnostic colonoscopies will be prevented.
Consequently, we find it highly likely that the project will change clinical practice.
Claus Lindbjerg Andersen
Professor, M.Sc., Ph.D.
Molekylær Medicinsk Afdeling, AUH