Introduction
Colorectal cancer (CRC) screening has been widely implemented, and recent advances in fecal immunochemical testing (FIT) have led to a shift in screening modalities from guaiac fecal occult blood testing (gFOBT) to FIT. In Japan, FIT was introduced into the national screening program in 1992, and a two-sample method has been offered to individuals aged 40 years and older. However, there is no standardized use of testing devices or cutoff values. Although hemoglobin concentrations of 100-150 ng/g are commonly used, few studies have evaluated cut-off values in population-based screening. An optimal cut-off value should be defined for adequate quality assurance by considering the benefits and harms of CRC screening.
Aims & Methods
To evaluate the optimal cutoff value for population-based screening, we compared the test performance of FIT according to different cutoff values. A total of 383,793 individuals participated in population-based screening in Ibaraki Prefecture from April 2021 to March 2023. The OC-sensor was used as the testing modality, with a default cut-off value of 100 ng/g. Test performance indicators, including positive rate, detection rate, positive predictive value (PPV), cancer miss rate, and number needed to scope (NNS), were assessed across cut-off values ranging from 100 to 250 ng/g. Detection rate, PPV, and NNS were explicitly calculated for CRC/ Advanced neoplasia (AN). Since the colonoscopy completion rate is typically around 70%, PPV and NNS were calculated on a per-protocol basis.
Results
Subjects who submitted two samples were 370419. Among them, 863 cases of CRC and 1944 cases of advanced adenomas were diagnosed. At a cutoff value of 100 ng/g at the baseline, the positive rate was 6.7% (95%CI: 6.7-6.8) and the colonoscopy completion rate was 76.0% (95%CI: 75.4-76.5) (Table). For AN, the detection rate was 0.76% (95%CI: 0.73-0.79), 14.8% for PPV (95%CI: 14.3-15.3), and 6.8% (95%CI: 6.5-7.0) for NNS. For CRC detection, the detection rate was 0.23% (95%CI: 0.22-0.25), 4.5% for PPV (95%CI: 4.3-4.8), and 22.0% (95%CI: 22.0-23.5) for NNS. The NNS decreased as the cutoff value increased, but the CRC miss rate also increased. The cutoff value reached 180 ng/g, the CRC miss rate became 19.5% (95%CI:16.8-22.1), whereas the positive rate was 4.2% (95%CI: 4.2-4.3), 0.19% (95%CI: 0.17-0.20) for CRC detection rate, 5.9% (95%CI: 5.5-6.3) for PPV, and 16.9 (95%CI: 15.8-18.2) for NNS.
Conclusion
The current cutoff value led to high detection rates for both CRC and AN, but it also required a greater number of colonoscopies. The availability of colonoscopy services varies across local municipalities and is often insufficient in rural areas. Adjusting the cutoff value is frequently used to address disparity in access to colonoscopy. However, the trade-off among benefits, harms, and resources is influenced by the social context, including individual preference and value. Therefore, an acceptable level of cancer miss rates should be carefully evaluated. Since the optimal cutoff value cannot be determined unequivocally, a comprehensive decision should be made by balancing benefits, harms, and resources, while also considering the preference of local residents.
References
Young GP, et al. Detection of advanced colorectal neoplasia and relative colonoscopy workloads using quantitative faecal immunochemical tests: an observational study exploring the effects of simultaneous adjustment of both sample number and test positivity threshold. BMJ Open Gastroenterol. 2020 ;7: e000517