In two studies reported in The New England Journal of Medicine, investigators found that a cell-free DNA (cfDNA) blood-based test (ECLIPSE study)1 and a next-generation multitarget stool DNA test (BLUE-C study)2 both showed high sensitivity for colorectal cancer and high specificity for advanced neoplasia (colorectal cancer and advanced precancerous lesions) in colorectal cancer screening compared with screening colonoscopy.
ECLIPSE Study
Daniel C. Chung, MD
As reported by Daniel C. Chung, MD, of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues,1 the U.S. multicenter study included 7,861 persons eligible for colorectal cancer screening enrolled between October 2019 and September 2022 who had results for colonoscopy and cfDNA test screening. Eligible participants were between the ages of 45 and 84 and at average risk for colorectal cancer. The co-primary outcome measures were cfDNA test sensitivity for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions) compared with screening colonoscopy. The secondary outcome measure was sensitivity in detecting advanced precancerous lesions.
cfDNA Test Performance
Among the 7,861 participants, colonoscopy showed colorectal cancer in 65, advanced precancerous lesions in 1,116, nonadvanced adenoma in 2,166, and negative results for colorectal neoplasia in 4,514.
A total of 83.1% of participants with colonoscopy-detected colorectal cancer had a positive cfDNA test, and 16.9% had a negative rest, yielding a cfDNA sensitivity for detection of colorectal cancer of 83.1% (95% confidence interval [CI] = 72.2%–90.3%). Sensitivity of the test was 87.5% (95% CI = 75.3%–94.1%) for stage I to III colorectal cancer and 13.2% (95% CI = 11.3%–15.3%) for advanced precancerous lesions.
A total of 89.6% of participants without colonoscopy-detected advanced colorectal neoplasia had a negative cfDNA test, and 10.4% had a positive cfDNA test, yielding a specificity of the cfDNA test for advanced neoplasia of 89.6% (95% CI = 88.8%–90.3%). The specificity of the test was 89.9% (95% CI = 89.0%–90.7%) for negative results for colorectal neoplasia on colonoscopy.
The investigators concluded: “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.”
BLUE-C Study
Thomas F. Imperiale, MD
As reported by Thomas F. Imperiale, MD, of Indiana University Melvin and Bren Simon Comprehensive Cancer Center and Regenstrief Institute, Indianapolis, and colleagues,2 the U.S. multicenter study included 20,176 participants (aged 40 years and older) who underwent colonoscopy screening, the next-generation stool DNA test, and the fecal immunochemical test (FIT) between November 2019 and January 2023. The primary outcome measures were sensitivity of the next-generation stool DNA test for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions) compared with colonoscopy findings.
Next-Generation Multitarget Stool DNA Test Performance
Among the 20,176 participants, colonoscopy screening showed that 98 had colorectal cancer, 2,144 had advanced precancerous lesions, 6,973 had nonadvanced adenomas, and 10,961 had no neoplastic findings (negative colonoscopy findings).
The next-generation test identified colorectal cancer in 92 of 98 participants with colonoscopy-detected colorectal cancer, yielding a sensitivity of 93.9% (95% confidence interval [CI] = 87.1%–97.7%). The test showed a specificity for advanced neoplasia of 90.6% (95% CI = 90.1%–91.0%). Sensitivity for advanced precancerous lesions was 43.4% (95% CI = 41.3%–45.6%). Specificity for negative colonoscopy findings was 92.7% (95% CI = 92.2%–93.1%).
Compared with colonoscopy findings, FIT showed sensitivity for colorectal cancer of 67.3% (95% CI = 57.1%–76.5%). Specificity for advanced neoplasia was 94.8% (95% CI = 94.4%–95.1%). Sensitivity for advanced precancerous lesions was 23.3% (95% CI = 21.5%–25.2%). Specificity for negative colonoscopy findings was 95.7% (95% CI = 95.3%–96.1%).
Compared with FIT, the next-generation test had significantly higher sensitivity for colorectal cancer (P < .001) and advanced precancerous lesions (P < .001) but significantly lower specificity for advanced neoplasia (P < .001).
The investigators concluded: “The next-generation multitarget stool DNA test showed higher sensitivity for colorectal cancer and advanced precancerous lesions than FIT but also showed lower specificity.”
William M. Grady, MD
William M. Grady, MD, of the Divisions of Public Health Sciences, Translational Science and Therapeutics, Fred Hutchinson Cancer Center, Seattle, is the corresponding author of The New England Journal of Medicine article on the ECLIPSE study. Dr. Imperiale is the corresponding author of the report on the BLUE-C study.
DISCLOSURE: The ECLIPSE study was funded by Guardant Health. The BLUE-C study was funded by Exact Sciences. For full disclosures of the study authors, visit nejm.org.
REFERENCES
1. Chung DC, Gray DM II, Singh H, et al: A cell-free DNA blood-based test for colorectal cancer screening. N Engl J Med 390:973-983, 2024.
2. Imperiale TF, Porter K, Zella J, et al: Next-generation multitarget stool DNA test for colorectal cancer screening. N Engl J Med 390:984-993, 2024.
