Multinational diagnostic accuracy study of a blood-based test for detection of advanced adenomas and colorectal cancer

Blood-based screening tests hold promise for increasing participation in colorectal cancer (CRC) screening, but their preventive effect remains limited if premalignant lesions are missed. The multinational DENEB study aimed to develop and evaluate a novel blood-based assay for detection of advanced colorectal adenomas and CRC. The blood-based test developed through discovery and training interrogated the transcriptional expression of 19 cell-free and 20 exosomal miRNAs using reverse transcription quantitative PCR. In the testing cohort (n=230), the test showed an area under the receiver operating characteristic curve of 95% (95% CI 92-98) for distinguishing CRCs and advanced adenomas from non-disease controls. Sensitivity for CRC of any stage was 91% (95% CI 80-96; 89% [75-96] for males and 95% [75-99] for females), while sensitivity for stage I, II, or III CRC was 92% (80-97). Sensitivy for advanced adenomas was 81% (95% CI 69-89; 82% [67-91] for males and 79% [57-92] for females). The specificity for advanced neoplasia was 85% (95% CI 77-90), while specificity for a negative colonoscopy was 83% (72-91). The authors conclude that these findings provide the rationale for advancing this assay into large-scale prospective studies to determine its performance, clinical utility, and potential role within population-based screening strategies.