Up to 9 Rounds of Fecal Immunochemical Test (FIT) Enhanced Interpretation of Positive and Negative for Colorectal Cancer Screening

Background: Fecal Immunochemical Tests (FIT) is intended for colonoscopy referral, when positive. Negative FIT is often dismissed, not knowing whether absence of cancer can be assured. Methods: A cohort of 513,283 adults successively went through health surveillance during 1994-2008 including initial FIT, with some returned up to 9 rounds. Colorectal cancer (CRC) (2138) were identified from Cancer Registry. CRC risk was expressed as NNS (number needed to scope for one CRC during study period). FIT(+) is defined as ≥ 20 µg hemoglobin/g feces based on OC-sensor method. Negative FIT was limited to “continuously negative” when interval cancer rate was calculated. Findings: Individuals with FIT(+), 3%-6% in each round, had risks widely variable by age and FIT values. Within one age group, quantitative FIT had CRC risks up to 10-fold difference. With identical FIT value (e.g. 60 µg /g), risks doubled in age 60 than age 50. "Continuously negative" FIT is unique with risk reduced each round by removing FIT(+), with 11-fold larger risks than FIT(-). A 37% risk reduction of initial FIT(-) increased to 90% by 5th round, without any intervention. Similar reduction existed for mortality. By 9th round, 79% of the cohort remained "continuously negative" with 90% risk reduced, having similar interval cancer rate as 10-year after negative colonoscopy. Interpretation: Positive FIT, expressed as NNS, predicts CRC risk, making colonoscopy referral more efficient, and "continuously negative" FIT for 5-9 rounds portends such reduced risk that 80% could spare the need for colonoscopy. These features help expand and promote FIT. Funding Statement: This study was supported in part by Taiwan Ministry of Health and Welfare Clinical Trial Center (MOHW108-TDU-B-212-133004). Declaration of Interests: The authors declare that they have no conflicts of interest. Ethics Approval Statement: The study was approved by the Institutional Review Boards at the National Health Research Institutes in Taiwan and informed consent obtained from each participant. All or part of the data used in this research were authorized by and received from MJ Health Research Foundation (Authorization Code: MJHRFB2014001C).