Colon to Rectum
Lancet Oncol. 2024;25(3):326–37
The multitarget fecal immunochemical test for improving stool-based colorectal cancer screening programs: A Dutch population-based, paired-design, intervention study
Background: The fecal immunochemical test (FIT) is widely employed for colorectal cancer (CRC) screening. However, its sensitivity for advanced precursor lesions remains suboptimal. The multitarget FIT (mtFIT), measuring hemoglobin, 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 utility of mtFIT versus FIT in a setting of population-based CRC screening.
Methods: Individuals aged 55–75 years and who were eligible for the Dutch national FIT-based CRC screening program were invited to submit both a FIT and mtFIT sample collected from the same bowel movement. Positive FIT (47 μg/g hemoglobin cut-off) 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 CRC, advanced adenoma, and advanced serrated polyps individually and the long-term effect of mtFIT-based versus FIT-based programmatic screening on CRC incidence, mortality, and cost, determined with microsimulation modelling.
Findings: Between March 25 and December 7, 2022, 35,786 individuals were invited to participate in the study, of whom 15,283 (42.7%) consented, and 13,187 of 15,283 (86.3%) 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% confidence interval [CI]: 8.62–9.61) positivity rate and a 2.27% (95% CI: 2.02–2.54) detection rate for advanced neoplasia, compared with a positivity rate of 4.08% (95% CI: 3.75–4.43) and a detection rate of 1.21% (95% CI: 1.03–1.41) for FIT. Detection rates of mtFIT versus FIT were 0.20% (95% CI: 0.13–0.29) versus 0.17% (95% CI: 0.11–0.27) for CRC; 1.64% (95% CI: 1.43–1.87) versus 0.86% (95% CI: 0.72–1.04) for advanced adenoma, and 0.43% (95% CI: 0.33–0.56) versus 0.17% (95% CI: 0.11–0.26) for advanced serrated polyps. Modelling demonstrated that mtFIT-based screening could reduce CRC incidence by 21% and associated mortality by 18% compared with the current Dutch CRC screening program, 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 CRC incidence by 5% and associated mortality by 4% compared with FIT-based screening.
Interpretation: The higher detection rate of multitarget fecal immunochemical test (mtFIT) for advanced adenoma compared with FIT holds the potential to translate into additional and clinically meaningful long-term colorectal cancer (CRC) incidence and associated mortality reductions in programmatic CRC screening.