Selecting a Cut-off for Colorectal Cancer Screening With a Fecal Immunochemical Test

OBJECTIVES: Fecal immunochemical tests (FITs) for hemoglobin (Hb) are increasingly used for colorectal cancer (CRC) screening. However, cut-offs for defining test positivity are varying widely. We aimed to evaluate the impact of cut-off selection on key indicators of diagnostic performance in a true screening setting. METHODS: We evaluated diagnostic performance of FOB Gold, a widely used quantitative FIT, for detecting advanced neoplasms (AN) across a wide range of possible cut-offs among 1822 participants of screening colonoscopy aged 50-79 years in Germany. RESULTS: The positive predictive value (PPV) for detecting AN showed a very steep increase with increasing cut-off up to 35.2% (95% CI 29.9-40.9%) at a cut-off of 9 mu g Hb/g feces at which sensitivity and specificity were 48.8% (95% CI 42.1-55.6%) and 88.5% (95% CI 86.8-89.9%), respectively. A further moderate increase of PPV up to 56.9% (95% CI 47.8-65.5%), along with a major decrease in sensitivity was observed when gradually increasing the cut-off to 25 mu g Hb/g feces at which sensitivity and specificity were 31.9% (95% CI 25.9-38.5%) and 96.9% (95% CI 95.9-97.6%), respectively. Further increases of the cut-off hardly affected PPV and specificity, but went along with further relevant decline in sensitivity. CONCLUSIONS: Our study illustrates delineation of a range of meaningful cut-offs (here: 9-25 mu g Hb/g feces) according to expected diagnostic yield in a true screening setting. Selecting a cut-off within or beyond this range should consider characteristics of the specific target population, such as AN prevalence or available colonoscopy capacity.