Clinical Validation of a Circulating Tumor DNA-Based Blood Test to Screen for Colorectal Cancer

Aasma Shaukat ^1,2, Carol A Burke ³, Andrew T Chan ⁴

¹NYU Grossman School of Medicine, New York, New York.
²University of Minnesota Twin Cities, Minneapolis.
³Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, Ohio.
⁴Massachusetts General Hospital, Boston, Massachusetts.
⁵Fred Hutchinson Cancer Center, Seattle, Washington.
⁶University of Washington School of Medicine, Seattle.
⁷University of California, San Diego.
⁸University of Pennsylvania Perelman School of Medicine, Philadelphia.
⁹Stanford University School of Medicine, Stanford, California.
¹⁰Morehouse School of Medicine, Atlanta, Georgia.
¹¹Freenome Holdings Inc, Brisbane, California.
¹²Now with Precision Medicine and Diagnostics, Los Altos Hills, California.
¹³Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
¹⁴Departments of Medicine and Epidemiology, University of Pittsburgh and the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
¹⁵Now with CBX Consulting LLC, San Jose, California.
¹⁶Now with Beacon Therapeutics, Alachua, Florida.
¹⁷Kaiser Permanente Division of Research, Pleasanton, California.

⁰NYU Grossman School of Medicine, New York, New York.

Jama +

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June 2, 2025

View abstract on PubMed

Summary

A new blood test shows promise for colorectal cancer screening, accurately detecting the disease in average-risk individuals. However, it struggles to identify precancerous lesions, indicating a need for further development to improve sensitivity.

Area Of Science

Oncology
Molecular Diagnostics
Preventive Medicine

Background

Colorectal cancer (CRC) screening is crucial but underutilized.
Blood-based screening tests offer potential for improved adherence over traditional methods.
Clinical validation of blood-based CRC tests in screening populations is essential.

Purpose Of The Study

To assess the clinical performance of an investigational blood-based circulating tumor DNA (ctDNA) test for CRC detection.
To evaluate the test's accuracy in an average-risk screening population using colonoscopy and histopathology as the reference standard.

Main Methods

A prospective, multicenter, cross-sectional observational study.
Enrolled 27,010 asymptomatic adults aged 45-85 at average risk for CRC.
Participants underwent blood collection for the ctDNA test followed by a screening colonoscopy; all parties were blinded to results.

Main Results

The blood test demonstrated a sensitivity of 79.2% for CRC and a specificity of 91.5% for advanced colorectal neoplasia.
Negative predictive value for advanced colorectal neoplasia was 90.8%, with a positive predictive value of 15.5%.
Sensitivity for advanced precancerous lesions was 12.5%, falling short of acceptance criteria.

Conclusions

The blood-based ctDNA test shows acceptable accuracy for detecting colorectal cancer in an average-risk screening population.
The test's ability to detect advanced precancerous lesions requires improvement.
Further research and development are necessary to enhance the test's sensitivity for precancerous conditions.