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

Caroline L Kahn ¹, Mathias M Petersen ², Jakob Kleif ³

¹Gastro Unit, Hvidovre Hospital, Hvidovre, Denmark.
²Gastro Unit, Hvidovre Hospital, Hvidovre, Denmark; Institute for Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
³Gastro Unit, Hvidovre Hospital, Hvidovre, Denmark; Institute for Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; Department of Surgery, Nordsjællands Hospital, Hillerød, Denmark.
⁴Institute for Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; Digestive Disease Center, Bispebjerg Hospital, Copenhagen, Denmark.
⁵Department of Surgery, Nordsjællands Hospital, Hillerød, Denmark.
⁶Gastro Unit, Section for Gastroenterology, Herlev Hospital, Herlev, Denmark.
⁷Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam UMC, AMC & VUMC, Amsterdam, The Netherlands.
⁸Department of Surgery, Randers Hospital, Randers, Denmark.
⁹Department of Surgery, Horsens Hospital, Horsens, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
¹⁰Department of Surgery, Viborg Hospital, Viborg, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
¹¹Department of Public Health Programmes and University Research Clinic for Cancer Screening, Randers Regional Hospital, Randers, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
¹²Clinical Genomics Pty Ltd, North Ryde, New South Wales, Australia.

⁰Gastro Unit, Hvidovre Hospital, Hvidovre, Denmark.

Clinical Colorectal Cancer +

|

April 9, 2025

View abstract on PubMed

Summary

A new dual-test approach using circulating tumor (ct)DNA markers alongside fecal immunochemical tests (FIT) significantly improves colorectal cancer (CRC) detection. This method enhances early diagnosis and could optimize screening by reducing unnecessary colonoscopies.

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.

Keywords:

Colonic cancer Early detection Population-based screening Predictive biomarkers Rectal cancer

Related Concept Videos

Serum Laboratory Studies, Stool Test, Breath Test

Gastrointestinal (GI) diagnostic studies are pivotal in confirming, ruling out, diagnosing, or staging various diseases, including cancers. Following diagnosis, allocating time for discussions with the patient and providing informational resources is crucial. Diagnostic assessments of the GI tract often occur in outpatient settings like endoscopy suites or GI labs. Preparation for these tests may include dietary restrictions, fasting, liquid bowel preparations, laxatives, enemas, and the...