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A multitarget stool DNA test detected more colorectal cancers (CRCs) than other testing but also resulted in more false-positives, according to a new study.

“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,” the study researchers wrote in The New England Journal of Medicine. “A simple, noninvasive test with high sensitivity for both colorectal cancer and advanced precancerous lesions might increase uptake and adherence rates, which could improve clinical outcomes.”

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Pros and Cons

Thomas Imperiale, MD, of the Indiana University School of Medicine, the Simon Cancer Center, and the Center for Innovation at Roudebush Veterans Affairs Medical Center in Indianapolis, IN, and colleagues compared a noninvasive, multitarget stool DNA test (Cologuard, Exact Sciences) with a commercially available fecal immunochemical test (FIT) for detection of CRC and precancerous lesions, defined as advanced adenomas or serrated polyps measuring at least 1 cm, in people at average risk.

The stool DNA test included assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and ß-actin as well as a hemoglobin immunoassay.

Dr. David Ransohoff
David Ransohoff, MD
Courtesy of the University of North Carolina
Lineberger Comprehensive Cancer Center

Of 12,776 participants enrolled in the study, 9,989 had fully evaluable samples. According to colonoscopy, prevalence of CRC was 0.7% (n = 65) and prevalence of advanced precancerous adenomas or sessile serrated polyps was 7.6% (n = 757).1

Results indicated that the sensitivity of the DNA test was 92.3% compared with 73.8% for the FIT (P=0.002) for detection of CRC. Similarly, sensitivity was higher with the DNA test for detection of precancerous lesions: 42.4% versus 23.8% for the DNA test and FIT, respectively (P<0.001).

Detection rates of polyps with high-grade dysplasia were 69.2% for the DNA test and 46.2% for the FIT (P=0.004). For serrated sessile polyps measuring at least 1 cm, detection rates were 42.4% and 5.1%, respectively (P<0.001).

Specificity, however, was lower for the DNA test as compared with the FIT, according to study data. For participants with findings other than CRC, including nonadvanced adenomas or negative findings, specificity was 86.6% for the DNA test and 94.9% for the FIT (P<0.001). Among those with completely negative results on colonoscopy, specificity was 89.8% and 96.4% for the DNA test and FIT, respectively (P<0.001).1

Further analyses showed that, in a hypothetical reference population of 10,000 people at average risk for CRC, the number of results deemed to be false-positives would be 76.4% with DNA testing and 67.2% with FIT.

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Additionally, the researchers found that, to detect one cancer, the number of people needed to be screened was 154 with colonoscopy, 166 with the DNA test, and 208 with FIT.

Study researcher David Ransohoff, MD, professor of medicine at the University of North Carolina (UNC) School of Medicine and UNC Lineberger Comprehensive Cancer Center in Chapel Hill, said that these results may have important clinical implications.

“Detection of 92% of colon cancers is extremely high for a noninvasive test, so that a negative test result means that no further evaluation, like colonoscopy, is needed at that time,” Dr. Ransohoff said in a press release. “Having such a sensitive, noninvasive option could have an important effect on screening rates for colorectal cancer.”