A Next-Generation Version of the Multitarget Stool DNA Test (Cologuard)

In 2014, a multitarget stool DNA test (Cologuard) was approved in the U.S. for colorectal cancer screening, based on a study that established the test's sensitivity and specificity (NEJM JW Gen Med May 1 2014 and N Engl J Med 2014; 370:1287). Now, industry-sponsored researchers present results of a study of a “next generation” stool DNA test, which contains more-recently identified markers of colorectal neoplasia (plus a test for fecal hemoglobin).

About 20,000 asymptomatic adults (mean age, 63) had stool specimens analyzed by the next-generation test and by a commercial fecal immunochemical (FIT) test for comparison; all participants then underwent colonoscopy. Colonoscopy identified colorectal cancer in 98 people and advanced precancerous lesions (but not cancer) in 2144 people. Findings for the next-generation test were as follows:

• Sensitivity was 94% for colorectal cancer and 43% for advanced precancerous lesions.
• Specificity (the proportion of people without cancer or advanced precancerous lesions whose test was negative) was 91%.
• Positive predictive value (the proportion of positive tests that were true positives for cancer or advanced neoplasia) was 11%.
• Negative predictive value (the proportion of negative tests that were true negatives for cancer or advanced neoplasia) was 93%.
• The stool DNA test was substantially more sensitive than FIT (94% vs. 67% for cancer; 43% vs. 23% for advanced precancerous lesions), but slightly less specific.