TY - JOUR
T1 - The multitarget faecal immunochemical test for improving stool-based colorectal cancer screening programmes
T2 - a Dutch population-based, paired-design, intervention study
AU - Wisse, Pieter H. A.
AU - de Klaver, Willemijn
AU - van Wifferen, Francine
AU - van Maaren-Meijer, Frejanne G.
AU - van Ingen, Huub E.
AU - Meiqari, Lana
AU - Huitink, Iris
AU - Bierkens, Mariska
AU - Lemmens, Margriet
AU - Greuter, Marjolein J. E.
AU - van Leerdam, Monique E.
AU - Spaander, Manon C. W.
AU - Dekker, Evelien
AU - Coupé, Veerle M. H.
AU - Carvalho, Beatriz
AU - de Wit, Meike
AU - Meijer, Gerrit A.
N1 - Publisher Copyright: © 2024 Elsevier Ltd
PY - 2024/3/1
Y1 - 2024/3/1
N2 - Background: The faecal immunochemical test (FIT) is widely employed for colorectal cancer screening. However, its sensitivity for advanced precursor lesions remains suboptimal. The multitarget FIT (mtFIT), measuring haemoglobin, calprotectin, and serpin family F member 2, has demonstrated enhanced sensitivity for advanced neoplasia, especially advanced adenomas, at equal specificity to FIT. This study aimed to prospectively validate and investigate the clinical utlitity of mtFIT versus FIT in a setting of population-based colorectal cancer screening. Methods: Individuals aged 55–75 years and who were eligible for the Dutch national FIT-based colorectal cancer screening programme were invited to submit both a FIT and mtFIT sample collected from the same bowel movement. Positive FIT (47 μg/g haemoglobin cutoff) or mtFIT (based on decision-tree algorithm) led to a colonoscopy referral. The primary outcome was the relative detection rate of mtFIT versus FIT for all advanced neoplasia. Secondary outcomes were the relative detection rates of colorectal cancer, advanced adenoma, and advanced serrated polyps individually and the long-term effect of mtFIT-based versus FIT-based programmatic screening on colorectal cancer incidence, mortality, and cost, determined with microsimulation modelling. The study has been registered in ClinicalTrials.gov, NCT05314309, and is complete. Findings: Between March 25 and Dec 7, 2022, 35 786 individuals were invited to participate in the study, of whom 15 283 (42·7%) consented, and 13 187 (86·3%) of 15 283 provided both mtFIT and FIT samples with valid results. Of the 13 187 participants, 6637 (50·3%) were male and 6550 (49·7%) were female. mtFIT showed a 9·11% (95% CI 8·62–9·61) positivity rate and 2·27% (95% CI 2·02–2·54) detection rate for advanced neoplasia, compared with a positivity rate of 4·08% (3·75–4·43) and a detection rate of 1·21% (1·03–1·41) for FIT. Detection rates of mtFIT versus FIT were 0·20% (95% CI 0·13–0·29) versus 0·17% (0·11–0·27) for colorectal cancer; 1·64% (1·43–1·87) versus 0·86% (0·72–1·04) for advanced adenoma, and 0·43% (0·33–0·56) versus 0·17% (0·11–0·26) for advanced serrated polyps. Modelling demonstrated that mtFIT-based screening could reduce colorectal cancer incidence by 21% and associated mortality by 18% compared with the current Dutch colorectal cancer screening programme, at feasible costs. Furthermore, at equal positivity rates, mtFIT outperformed FIT in terms of diagnostic yield. At an equally low positivity rate, mtFIT-based screening was predicted to further decrease colorectal cancer incidence by 5% and associated mortality by 4% compared with FIT-based screening. Interpretation: The higher detection rate of mtFIT for advanced adenoma compared with FIT holds the potential to translate into additional and clinically meaningful long-term colorectal cancer incidence and associated mortality reductions in programmatic colorectal cancer screening. Funding: Stand Up to Cancer, Dutch Cancer Society, Dutch Digestive Foundation, and Health~Holland.
AB - Background: The faecal immunochemical test (FIT) is widely employed for colorectal cancer screening. However, its sensitivity for advanced precursor lesions remains suboptimal. The multitarget FIT (mtFIT), measuring haemoglobin, calprotectin, and serpin family F member 2, has demonstrated enhanced sensitivity for advanced neoplasia, especially advanced adenomas, at equal specificity to FIT. This study aimed to prospectively validate and investigate the clinical utlitity of mtFIT versus FIT in a setting of population-based colorectal cancer screening. Methods: Individuals aged 55–75 years and who were eligible for the Dutch national FIT-based colorectal cancer screening programme were invited to submit both a FIT and mtFIT sample collected from the same bowel movement. Positive FIT (47 μg/g haemoglobin cutoff) or mtFIT (based on decision-tree algorithm) led to a colonoscopy referral. The primary outcome was the relative detection rate of mtFIT versus FIT for all advanced neoplasia. Secondary outcomes were the relative detection rates of colorectal cancer, advanced adenoma, and advanced serrated polyps individually and the long-term effect of mtFIT-based versus FIT-based programmatic screening on colorectal cancer incidence, mortality, and cost, determined with microsimulation modelling. The study has been registered in ClinicalTrials.gov, NCT05314309, and is complete. Findings: Between March 25 and Dec 7, 2022, 35 786 individuals were invited to participate in the study, of whom 15 283 (42·7%) consented, and 13 187 (86·3%) of 15 283 provided both mtFIT and FIT samples with valid results. Of the 13 187 participants, 6637 (50·3%) were male and 6550 (49·7%) were female. mtFIT showed a 9·11% (95% CI 8·62–9·61) positivity rate and 2·27% (95% CI 2·02–2·54) detection rate for advanced neoplasia, compared with a positivity rate of 4·08% (3·75–4·43) and a detection rate of 1·21% (1·03–1·41) for FIT. Detection rates of mtFIT versus FIT were 0·20% (95% CI 0·13–0·29) versus 0·17% (0·11–0·27) for colorectal cancer; 1·64% (1·43–1·87) versus 0·86% (0·72–1·04) for advanced adenoma, and 0·43% (0·33–0·56) versus 0·17% (0·11–0·26) for advanced serrated polyps. Modelling demonstrated that mtFIT-based screening could reduce colorectal cancer incidence by 21% and associated mortality by 18% compared with the current Dutch colorectal cancer screening programme, at feasible costs. Furthermore, at equal positivity rates, mtFIT outperformed FIT in terms of diagnostic yield. At an equally low positivity rate, mtFIT-based screening was predicted to further decrease colorectal cancer incidence by 5% and associated mortality by 4% compared with FIT-based screening. Interpretation: The higher detection rate of mtFIT for advanced adenoma compared with FIT holds the potential to translate into additional and clinically meaningful long-term colorectal cancer incidence and associated mortality reductions in programmatic colorectal cancer screening. Funding: Stand Up to Cancer, Dutch Cancer Society, Dutch Digestive Foundation, and Health~Holland.
UR - http://www.scopus.com/inward/record.url?scp=85184746604&partnerID=8YFLogxK
U2 - 10.1016/S1470-2045(23)00651-4
DO - 10.1016/S1470-2045(23)00651-4
M3 - Article
C2 - 38346438
SN - 1470-2045
VL - 25
SP - 326
EP - 337
JO - The Lancet Oncology
JF - The Lancet Oncology
IS - 3
ER -