Abstract
BACKGROUND: Many screening programs for colorectal cancer (CRC) use the fecal immunochemical test (FIT) to triage individuals for colonoscopy. Although these programs reduce CRC incidence and CRC-related mortality, the detection of advanced precursor lesions (advanced adenomas and advanced serrated polyps) by FIT could be improved. As an alternative for FIT, the antibody-based multitargetFIT (mtFIT) has been proposed. The mtFIT measures three protein markers: hemoglobin, calprotectin, and serpin family F member 2. In a retrospective diagnostic accuracy study in a large colonoscopy-controlled series (n = 1284), mtFIT showed increased sensitivity for advanced neoplasia (AN), at equal specificity, compared to FIT (42.9% versus 37.3%; p = 0.025). This increase was mainly due to a higher sensitivity of mtFIT for advanced adenomas (37.8% versus 28.1% for FIT; p = 0.006). The present mtFIT study aims to prospectively validate these findings in the context of the Dutch national CRC screening program. METHOD: The mtFIT study is a cross-sectional intervention study with a paired design. Eligible subjects for the Dutch FIT-based national CRC screening program are invited to perform mtFIT in addition to FIT. Samples are collected at home, from the same bowel movement, and are shipped to a central laboratory by postal mail. If either one or both tests are positive, participants are referred for colonoscopy. Detailed colonoscopy and pathology data are centrally stored in a national screening database (ScreenIT; Topicus, Deventer, the Netherlands) that is managed by the screening organization, and will be retrieved for this study. We aim to determine the relative sensitivity for AN, comprising of CRC, advanced adenomas and advanced serrated polyps, of mtFIT compared to FIT at an equal positivity rate. Additionally, we will use the Adenoma and Serrated Pathway to Colorectal CAncer model to predict lifetime health effects and costs for programmatic mtFIT- versus FIT-based screening. The target sample size is 13,131 participants. DISCUSSION: The outcome of this study will inform on the comparative clinical utility of mtFIT versus FIT in the Dutch national CRC screening program and is an important step forward in the development of a new non-invasive stool test for CRC screening. TRIAL REGISTRATION: Clinicaltrials.gov ; NCT05314309, registered April 6th 2022, first inclusions March 25th 2022 https://clinicaltrials.gov/ct2/results?cond=&term=NCT05314309&cntry=&state=&city=&dist =.
| Original language | English |
|---|---|
| Article number | 1299 |
| Journal | BMC Cancer |
| Volume | 22 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 12 Dec 2022 |
Bibliographical note
Funding Information:We thank the screening organization, the National Institute for Public Health and the Environment and the executing laboratory for their important contributions to this work. In addition, Health-RI is acknowledged for providing and enabling the research infrastructure. The study was done within the frame of the European Cooperation in Science and Technology (COST) Action (CA17118) and supported by COST. The first enrolment into the study occurred in March 2022. The study is currently recruiting participants. Primary sponsor: Netherlands Cancer Institute. Contact person / principal investigator: Prof. Dr. G.A. Meijer. Contact address: Plesmanlaan 121, 1066 CX Amsterdam. Department: Pathology. Email: [email protected] Secondary sponsors: - Erasmus MC. Contact person: Prof. Dr. M.C.W. Spaander. Department: Gastroenterology and hepatology. Contact address: Doctor Molewaterplein 40, 3015 GD Rotterdam. - Amsterdam UMC location AMC. Contact person: Prof. Dr. E. Dekker. Department: Gastroenterology and hepatology. Contact address: Meibergdreef 9, 1105 AZ Amsterdam. The primary and secondary sponsors and other funders have no role in the study design, interpretation of data, and the decision to submit the report for publication. A steering committee was established, encompassing representatives from the research team, the National Institute for Public Health and the Environment, and the screening organization. The steering committee meets every 3 months during the execution of the study to discuss the progress. Working group meetings are held weekly with representatives from the research team, data management team, screening organization and laboratory.
Funding Information:
MdW is co-founder and board member (COO) of CRCbioscreen BV. MCWS has received research support from: Sentinel, Sysmex, Norgine, and Medtronic. ED has endoscopic equipment on loan of Olympus and FujiFilm, and received a research grant from FujiFilm. She has received honorarium for consultancy from FujiFilm, Tillots, Olympus, GI Supply, Cancer Prevention Pharmaceuticals, PAION and Ambu, and speakers' fees from Olympus, Roche, GI Supply, Norgine, IPSEN, PAION and FujiFilm. BC, MdW, VMHC and GAM have several patents pending and/or issued.
Funding Information:
We thank the screening organization, the National Institute for Public Health and the Environment and the executing laboratory for their important contributions to this work. In addition, Health-RI is acknowledged for providing and enabling the research infrastructure. The study was done within the frame of the European Cooperation in Science and Technology (COST) Action (CA17118) and supported by COST.
Publisher Copyright:
© 2022, The Author(s).
