Multitarget Stool DNA Testing for Colorectal-Cancer Screening

BackgroundAn accurate, noninvasive test could improve the effectiveness of colorectal-cancer screening. MethodsWe compared a noninvasive, multitarget stool DNA test with a fecal immunochemical test (FIT) in persons at average risk for colorectal cancer. The DNA test includes quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and -actin, plus a hemoglobin immunoassay. Results were generated with the use of a logistic-regression algorithm, with values of 183 or more considered to be positive. FIT values of more than 100 ng of hemoglobin per milliliter of buffer were considered to be positive. Tests were processed independently of colonoscopic findings. ResultsOf the 9989 participants who could be evaluated, 65 (0.7%) had colorectal cancer and 757 (7.6%) had advanced precancerous lesions (advanced adenomas or sessile serrated polyps measuring 1 cm in the greatest dimension) on colonoscopy. The sensitivity for detecting colorectal cancer was 92.3% with DNA testing and 73.8% with FIT (P=0.002). The sensitivity for detecting advanced precancerous lesions was 42.4% with DNA testing and 23.8% with FIT (P<0.001). The rate of detection of polyps with high-grade dysplasia was 69.2% with DNA testing and 46.2% with FIT (P=0.004); the rates of detection of serrated sessile polyps measuring 1 cm or more were 42.4% and 5.1%, respectively (P<0.001). Specificities with DNA testing and FIT were 86.6% and 94.9%, respectively, among participants with nonadvanced or negative findings (P<0.001) and 89.8% and 96.4%, respectively, among those with negative results on colonoscopy (P<0.001). The numbers of persons who would need to be screened to detect one cancer were 154 with colonoscopy, 166 with DNA testing, and 208 with FIT. ConclusionsIn asymptomatic persons at average risk for colorectal cancer, multitarget stool DNA testing detected significantly more cancers than did FIT but had more false positive results. (Funded by Exact Sciences; ClinicalTrials.gov number, NCT01397747.) A stool test that measures mutant KRAS, abnormal gene methylation, and hemoglobin detected significantly more colorectal cancers than a commercial fecal immunochemical test (FIT) but had more false positive results. Colorectal cancer is a major cause of death and disease among men and women in the United States.(1) The underlying neoplastic processes of colorectal carcinogenesis lend themselves to screening.(2) Evidence supports and guidelines endorse several tests and strategies,(3)-(5) and screening for colorectal cancer has been found to be cost-effective.(5)-(7) Despite the supporting evidence, recommendations, and availability of several screening tests, a substantial proportion of the U.S. population is not up to date with screening.(8) A simple, noninvasive test with high sensitivity for both colorectal cancer and advanced precancerous lesions might increase uptake and adherence rates, which could improve ...