Accuracy of the Quantitative Fecal Immunochemical Test (FIT) for Colorectal Cancer and Advanced Adenoma Detection: an Updated Systematic Review and Meta-Analysis: Presidential Poster Award

Introduction: Quantitative fecal hemoglobin immunochemical tests (FITs) are the most commonly used screening tests for colorectal cancer worldwide. We quantified the change in colorectal cancer and advanced adenoma detection and number of positive tests at different positivity thresholds for quantitative FIT and differences in FIT performance by sex and age. Methods: We updated a 2014 systematic review by searching MEDLINE and EMBASE between January 2012 and May 2018. We included studies that evaluated the sensitivity and specificity of quantitative FIT for colorectal cancer and advanced adenoma detection in asymptomatic, average-risk adults using colonoscopy as the reference standard. We summarized studies that stratified by sex and age and performed stratified analyses by positivity threshold. The number of cancers, advanced adenomas, and positive tests from a theoretical screening cohort of 100,000 participants was calculated at positivity thresholds ≤10, 10 to ≤15, 15 to ≤20, 20 to ≤30, and >30 μg hemoglobin/g feces. Results: We included 40 eligible articles describing 50 studies, including 38 studies with colonoscopy follow-up of all participants. Of the five studies that investigated sex-specific diagnostic performance, four studies showed higher sensitivity and lower specificity in men than women; and of the four studies that investigated age-specific diagnostic performance, 3 studies showed decreasing sensitivity and specificity with increasing age. Stratified analyses of studies with colonoscopy follow-up showed that sensitivity for colorectal cancer increased from 66% (95%CI 57-73) for studies with a threshold of >30 μg/g to 81% (95%CI 77-84) for studies with a threshold ≤10 μg/g, while specificity decreased from 96% (95%CI 95-97) to 91% (95%CI 89-93). Sensitivity for advanced adenomas increased from 20% (95%CI 16-25) to 30% (95%CI 27-34). A threshold of ≤10 μg/g would detect 70 more cancers and 540 more advanced adenomas than a threshold of >30 μg/g per 100,000 participants, with 5,047 additional positive tests (Figure). Conclusion: FIT sensitivity for colorectal cancer appears to be higher and specificity lower in men than women, while trends in sensitivity and specificity with increasing age are less clear. Decreasing the positivity threshold from >30 μg/g to ≤10 μg/g results in the detection of 23% more cancers and 50% more advanced adenomas, and generates 118% more positive tests requiring colonoscopy.252 Figure 1. Quantitative fecal immunochemical test performance at varying quantitative thresholds in a theoretical cohort of 100,000 average risk adults. Panel A: Number of cancers detected. Panel B: Number of advanced adenomas detected, defined as adenomas ≥10 mm, villous structure and/or any high-grade dysplasia. Panel C: Number of positive tests requiring colonoscopy follow-up. Cancer and advanced adenoma prevalence based on pooled prevalence of prospective cohort studies with colonoscopy follow-up. Error bars represent 95% confidence intervals generated from pooled estimates of sensitivity and specificity.