Plausibility of an extensive use of stool DNA test for screening advanced colorectal neoplasia

Purpose: FIT-DNA test is supposed to be highly sensitive for advanced colorectal neoplasms and is advocated in some developed countries, but lack extensive use in developing countries. Methods: A case control study on stool DNA test for colorectal neoplasms patients was conducted from March 2016 to October 2017 in China. We recruited CRC, colorectal neoplasms and normal controls from ambulatory patients and screening attendees in communities. The stool DNA was tested by a molecular panel similar as ColoGuard in addition to fecal immunochemical test(FIT) in a blinded manner. A risk scoring system was used to determine the positiveness of tests with histological diagnosis as its reference standard. Results: Eligible subjects included 203 colorectal cancer (CRC), 49 advanced adenoma (AA), 156 non-advanced adenoma(NAA) and 431 normal controls(NC). The FIT-DNA kit detected 97.5% CRC (n = 198, 95% CI = 95.4-99.7) and 53.1% AA (n = 26, 95% CI = 39.1-67.0), with specificity of 89.1% (95% CI = 86.2-92.0) in NC and 88.1% (95% CI = 85.5-90.7) in non-advanced controls. The FIT embedded in the kit alone identified 94.6% (n = 192, 95% CI = 91.5-97.7) CRC and 36.7% AA (n = 18, 95% CI = 23.2-50.2). Consistency of KRAS mutation, BMP3 methylation, NDRG4 methylation in 26 paires stool DNA and CRC tumor DNA were 80.9%, 71.4% and 81.8%, respectively. Conclusion: At the sacrifice of significantly decreased specificity, a FIT-DNA kit may has better sensitivity than FIT for predicting advanced colorectal adenoma, but not for predicting colorectal cancer. More evidences are needed for the extensive use of FIT-DNA testing.