A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening

Daniel C Chung; Darrell M Gray 2nd; Harminder Singh; Rachel B Issaka; Victoria M Raymond; Craig Eagle; Sylvia Hu; Darya I Chudova; AmirAli Talasaz; Joel K Greenson; Frank A Sinicrope; Samir Gupta; William M Grady

doi:10.1056/NEJMoa2304714

A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening

N Engl J Med. 2024 Mar 14;390(11):973-983. doi: 10.1056/NEJMoa2304714.

Affiliation

¹ From the Division of Gastroenterology and Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston (D.C.C.); Gray Area Strategies, Owings Mills, MD (D.M.G.); the Association of Black Gastroenterologists and Hepatologists, New York (D.M.G.); the Departments of Internal Medicine and Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba and Paul Albrechtsen Research Institute CancerCare Manitoba, Winnipeg, Canada (H.S.); the Divisions of Public Health Sciences (R.B.I., W.M.G.), Clinical Research (R.B.I.), and Translational Science and Therapeutics (W.M.G.), Fred Hutchinson Cancer Center, and the Division of Gastroenterology, University of Washington School of Medicine (R.B.I., W.M.G.) - both in Seattle; Guardant Health, Palo Alto (V.M.R., C.E., S.H., D.I.C., A.T.), and the University of California, San Diego, La Jolla (S.G.) - both in California; the Department of Pathology, Michigan Medicine, Ann Arbor (J.K.G.); and the Divisions of Oncology, Gastroenterology, and Hepatology, Mayo Clinic, Mayo Comprehensive Cancer Center and Mayo Alix School of Medicine, Rochester, MN (F.A.S.).

PMID: 38477985
DOI: 10.1056/NEJMoa2304714

Abstract

Background: Colorectal cancer is the third most diagnosed cancer in adults in the United States. Early detection could prevent more than 90% of colorectal cancer-related deaths, yet more than one third of the screening-eligible population is not up to date with screening despite multiple available tests. A blood-based test has the potential to improve screening adherence, detect colorectal cancer earlier, and reduce colorectal cancer-related mortality.

Methods: We assessed the performance characteristics of a cell-free DNA (cfDNA) blood-based test in a population eligible for colorectal cancer screening. The coprimary outcomes were sensitivity for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions) relative to screening colonoscopy. The secondary outcome was sensitivity to detect advanced precancerous lesions.

Results: The clinical validation cohort included 10,258 persons, 7861 of whom met eligibility criteria and were evaluable. A total of 83.1% of the participants with colorectal cancer detected by colonoscopy had a positive cfDNA test and 16.9% had a negative test, which indicates a sensitivity of the cfDNA test for detection of colorectal cancer of 83.1% (95% confidence interval [CI], 72.2 to 90.3). Sensitivity for stage I, II, or III colorectal cancer was 87.5% (95% CI, 75.3 to 94.1), and sensitivity for advanced precancerous lesions was 13.2% (95% CI, 11.3 to 15.3). A total of 89.6% of the participants without any advanced colorectal neoplasia (colorectal cancer or advanced precancerous lesions) identified on colonoscopy had a negative cfDNA blood-based test, whereas 10.4% had a positive cfDNA blood-based test, which indicates a specificity for any advanced neoplasia of 89.6% (95% CI, 88.8 to 90.3). Specificity for negative colonoscopy (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95% CI, 89.0 to 90.7).

Conclusions: In an average-risk screening population, this cfDNA blood-based test had 83% sensitivity for colorectal cancer, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions. (Funded by Guardant Health; ECLIPSE ClinicalTrials.gov number, NCT04136002.).

Publication types

Clinical Study
Validation Study

MeSH terms

Adult
Cell-Free Nucleic Acids* / blood
Colonoscopy
Colorectal Neoplasms* / blood
Colorectal Neoplasms* / diagnosis
Early Detection of Cancer* / methods
Humans
Mass Screening* / methods
Precancerous Conditions* / blood
Precancerous Conditions* / diagnosis
Sensitivity and Specificity

Substances

Cell-Free Nucleic Acids

Associated data

ClinicalTrials.gov/NCT04136002

Grants and funding

K08 CA241296/CA/NCI NIH HHS/United States