Performance of a quantitative fecal immunochemical test for detecting advanced colorectal neoplasia: a prospective cohort study

Background: The fecal immunochemical test (FIT) is easier to use and more sensitive than the guaiac fecal occult blood test, but it is unclear how to optimize FIT performance. We compared the sensitivity and specificity for detecting advanced colorectal neoplasia between single-sample (1-FIT) and two-sample (2-FIT) FIT protocols at a range of hemoglobin concentration cutoffs for a positive test. Methods: We recruited 2,761 average-risk men and women ages 49-75 referred for colonoscopy within a large nonprofit, group-model health maintenance organization (HMO), and asked them to complete two separate single-sample FITs. We generated receiver-operating characteristic (ROC) curves to compare sensitivity and specificity estimates for 1-FIT and 2-FIT protocols among those who completed both FIT kits and colonoscopy. We similarly compared sensitivity and specificity between hemoglobin concentration cutoffs for a single-sample FIT. Results: Differences in sensitivity and specificity between the 1-FIT and 2-FIT protocols were not statistically significant at any of the pre-specified hemoglobin concentration cutoffs (10, 15, 20, 25, and 30 mu g/g). There was a significant difference in test performance of the one-sample FIT between 50 ng/ml (10 mu g/g) and each of the higher pre-specified cutoffs. Disease prevalence was low. Conclusions: A two-sample FIT is not superior to a one-sample FIT in detection of advanced adenomas; the one-sample FIT at a hemoglobin concentration cutoff of 50 ng/ml (10 mu g/g) is significantly more sensitive for advanced adenomas than at higher cutoffs. These findings apply to a population of younger, average-risk patients in a U.S. integrated care system with high rates of prior screening.