In the BLUE-C study—reported in The New England Journal of Medicine—Imperiale et al found that a next-generation multitarget stool DNA test showed high sensitivity for colorectal cancer and high specificity for advanced neoplasia compared with colonoscopy screening.
Study Details
The U.S. multicenter study included 20,176 participants aged ≥ 40 years who underwent colonoscopy screening, the next-generation stool DNA test, and fecal immunochemical testing (FIT). The primary outcomes 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 better 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.”
Thomas F. Imperiale, MD, of Indiana University School of Medicine, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, and Regenstrief Institute, Indianapolis, is the corresponding author for The New England Journal of Medicine article.
Disclosure: The study was funded by Exact Sciences. For full disclosures of the study authors, visit nejm.org.
