High accuracy of a blood ctDNA-based multimodal test to detect colorectal cancer

Background: Detection of circulating tumor DNA (ctDNA) is a minimally invasive and convenient blood-based screening strategy that may increase effectiveness of colorectal cancer (CRC) screening.

Patients and methods: A novel multimodal ctDNA-based blood assay that integrates genomics, epigenomics and fragmentomics, as well as proteomics in a refined version, was tested in blood samples from two cohorts: (i) consecutive fecal immunochemical test (FIT)-positive individuals from the CRC Barcelona stool-based screening program; (ii) patients diagnosed with CRC. Primary endpoint was the performance of the test to detect CRC at different tumor-node-metastasis (TNM) stages. Secondary endpoint was the ability of the test to detect advanced precancerous lesions (advanced adenoma or advanced serrated lesion).

Results: A total of 623 blood samples were analyzed in the primary analysis. Sensitivity and specificity of the assay to detect CRC was 93% and 90%, respectively. The sensitivity of CRC detection according to TNM stages was 84% for stage I, 94% for stage II and 96% for stage III (70/73) (P< 0.024). Sensitivity to detect advanced precancerous lesions was 23% with a refined version of the test (including protein and updating bioinformatic thresholding).

Conclusion: A blood-based multimodal ctDNA assay detected CRC with high accuracy. This minimally invasive, accessible and convenient assay may help to increase the effectiveness of CRC screening.