Colon to Rectum
N Engl J Med. 2024;390(11):984–93
Next-generation multitarget stool DNA test for colorectal cancer screening
Background: A next-generation multitarget stool DNA test, including assessments of DNA molecular markers and hemoglobin level, was developed to improve the performance of colorectal cancer screening, primarily with regard to specificity.
Methods: In a prospective study, the authors evaluated a next-generation multitarget stool DNA test in asymptomatic adults 40 years of age or older who were undergoing screening colonoscopy. The primary outcomes were sensitivity of the test for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions). Advanced precancerous lesions included 1 or more adenomas or sessile serrated lesions measuring at least 1 cm in the longest dimension, lesions with villous histologic features, and high-grade dysplasia. Secondary objectives included the quantification of sensitivity for advanced precancerous lesions and specificity for non-neoplastic findings or negative colonoscopy and comparison of sensitivities for colorectal cancer and advanced precancerous lesions between the multitarget stool DNA test and a commercially available fecal immunochemical test (FIT).
Results: Of 20,176 participants, 98 had colorectal cancer, 2144 had advanced precancerous lesions, 6973 had non-advanced adenomas, and 10,961 had non-neoplastic findings or negative colonoscopy. With the next-generation test, sensitivity for colorectal cancer was 93.9% (95% confidence interval [CI]: 87.1–97.7), and specificity for advanced neoplasia was 90.6% (95% CI: 90.1–91.0). Sensitivity for advanced precancerous lesions was 43.4% (95% CI: 41.3–45.6), and specificity for non-neoplastic findings or negative colonoscopy was 92.7% (95% CI: 92.2–93.1). With the FIT, sensitivity was 67.3% (95% CI: 57.1–76.5) for colorectal cancer and 23.3% (95% CI: 21.5–25.2) for advanced precancerous lesions; specificity was 94.8% (95% CI: 94.4–95.1) for advanced neoplasia and 95.7% (95% CI: 95.3–96.1) for non-neoplastic findings or negative colonoscopy. As compared with FIT, the next-generation test had superior sensitivity for colorectal cancer (p < 0.001) and for advanced precancerous lesions (p < 0.001) but had lower specificity for advanced neoplasia (p < 0.001). No adverse events occurred.
Conclusions: The next-generation multitarget stool DNA test showed higher sensitivity for colorectal cancer and advanced precancerous lesions than fecal immunochemical test but also showed lower specificity.