Individualized faecal immunochemical test cut-off based on age and sex in colorectal cancer screening

The risk of having colorectal cancer (CRC) or its precursors vary with age and sex. Yet, most CRC screening programs using the quantitative faecal immunochemical test (FIT) use a uniform FIT cut-off. We aimed to calculate individualized FIT cut-offs based on age and sex. Data from a study of 1,112 asymptomatic average-risk screening participants undergoing colonoscopy without preselection were used to build a logistic regression model to calculate the risk of having advanced neoplasia (AN) at colonoscopy using age, sex, and FIT concentration as variables. We calculated age- and sex-adjusted FIT cut-off concentrations based on a uniform risk threshold. In a total of 101 of the 1,112 participants AN was detected at colonoscopy. We selected a risk threshold that would produce a specificity of 96.9% in the study group, matching the specificity of FIT at a cut-off of 20 µg Hb/g faeces. At this threshold, age- and sex-adjusted FIT cut-off concentrations ranged from 36.9 µg Hb/g faeces for 50-year-old women to 9.5 µg Hb/g faeces for 75-year old men. At this level of specificity, the risk-based model reached a sensitivity for AN of 28.7% (95%CI: 20.8 to 38.2) versus 27.7% (95%CI: 19.9 to 37.1) for FIT only. Using a risk threshold instead of a uniform FIT-based threshold for inviting screening participants to follow-up colonoscopy ensures that everyone has a comparable risk of AN prior to colonoscopy and may improve the detection of advanced neoplasia, although the absolute magnitude of the increase is likely to be limited.