Circulating Tumor DNA in Addition to Fecal Immunochemical Test in a Dual-Test Colorectal Cancer Screening Approach

Area of Science:

• Oncology
• Molecular Diagnostics
• Gastroenterology

Background:

• Colorectal cancer (CRC) screening aims to reduce incidence and mortality.
• Fecal immunochemical tests (FIT) are standard but have limited specificity, straining colonoscopy resources.
• Circulating tumor (ct)DNA markers offer potential for improved early CRC detection.

Purpose of the Study:

• To evaluate ctDNA markers (BCAT1, IKZF1, IRF4) in a dual-test strategy for early CRC detection.
• To assess the performance of this dual-test approach in FIT-positive individuals.
• To benchmark the dual-test against FIT alone for optimizing screening efficiency.

Main Methods:

• Plasma samples from 774 FIT-positive individuals were analyzed for hypermethylated ctDNA markers.
• Multivariate logistic regression models incorporated ctDNA markers and age with FIT values.
• The dual-test approach was compared to FIT alone using Area Under the Curve (AUC) metrics.

Main Results:

• The dual-test approach demonstrated superior CRC detection (AUC 87.2%) compared to FIT alone (AUC 72.5%).
• Performance improved for detecting advanced adenomas as well (AUC 71.8% vs 65.5%).
• The dual-test strategy could reduce colonoscopy needs by up to 56% or increase CRC detection by 28%.

Conclusions:

• A dual-test approach combining ctDNA markers with FIT enhances sensitivity and specificity for CRC detection.
• This strategy is effective in asymptomatic individuals, improving early diagnosis rates.
• ctDNA panels can optimize CRC screening protocols, particularly when FIT cutoffs are adjusted.