Evaluation of Cell-free DNA Long Fragments in the Triage of FIT+ Patients Enrolled in a Colorectal Cancer Screening Program: An Italian Prospective, Cross-Sectional Study

Background: Colorectal Cancer screening programs are effective in reducing incidence and mor-tality. In Europe, every FIT+ patient is referred to colonoscopy. Available data shows that ~75.0% of these patients are negative. It is desirable to select patients at greater risk of having a positive colonoscopy. Methods: 711 subjects, aged 50-74, attending the screening program of ASL-NA-3-SUD (Na-ples, Italy), were enrolled in a cross-sectional study to evaluate the performance of QuantiDNA™ test and non-inferiority of an alternative approach (AAP). This evaluation is based on FIT+ and QuantiDNA™+ patients referred to colonoscopy, compared to Standard of Care (SOC), colon-oscopy following a FIT+ test alone. A non-inferiority margin for Colorectal Neoplasia (CN) and Advanced Adenomas (AA) was set at -10% and at -3.8% for CRC. Results: The odds ratio was 1.76 (p-value= 0.009). The detection rate of AAP was 15.9% for colorectal neoplasia (CN), 13.0% for advanced adenoma (AA), and 3.0% for CRC. The risk dif-ference between AAP and SOC was -5.07% (95% C.I -9.23, -0.90) for CN, -4.02% (95% C.I. -7.89, -0.16) for AA, and -1.04% (95% C.I. -3.16, 1.07) for CRC. This data suggests that AAP is non-inferior to SOC for detecting CN, AA, and CRC. The expected decrease in colonoscopies is 33.4%. Conclusions: The QuantiDNA™ test is straightforward, non-invasive, and well-tolerated. Data from this study indicates it is effective in the reduction of the need for colonoscopy examina-tions (-33.4%) and is non-inferior to SOC in the detection of significant colorectal lesions.