Stool DNA Test Sensitive for Large Sessile Serrated Polyps

Caroline Helwick

May 12, 2014

CHICAGO — The detection rate of sessile serrated polyps that are at least 1 cm in size is almost 10 times higher with the Cologuard multitarget stool DNA test, from Exact Sciences, than with the fecal immunochemical test (FIT), results from the DEEP-C study show.

The stool DNA test, which was unanimously endorsed in March by a panel of advisers from the US Food and Drug Administration, consists of quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, β-actin, and a hemoglobin immunoassay.

"The sensitivity of stool DNA for sessile serrated polyps 1 cm and larger was significantly higher than FIT," said investigator Barry Berger, MD, chief medical officer at Exact Sciences in Madison, Wisconsin. "FIT was not effective for identifying patients with large polyps," he explained.

Dr. Berger presented findings from a prespecified analysis here at Digestive Disease Week 2014. Results were also published in the April 3 issue of the New England Journal of Medicine (2014;370:1287-1297).

Frequent Precursors to Cancer and Hard to Spot

Sessile serrated polyps are precursors to approximately one-third of colorectal cancers. They are more challenging to identify endoscopically than conventional adenomas because they are typically flat, located in the proximal colon, and nonhemorrhagic.

"They are much harder to detect with colonoscopy. And they don't bleed, so they are not detected with fecal blood testing. Stool DNA testing is really the only noninvasive approach to detecting these lesions," explained David Ahlquist, MD, professor of medicine at the Mayo Clinic in Rochester, Minnesota, and another of the study investigators.

DEEP-C Details

DEEP-C was a head-to-head comparison of stool DNA testing and FIT. It involved 9989 average-risk people 50 to 84 years of age from 90 sites in the United States. Mean age was 64 years.

A single stool sample collected from each patient prior to colonoscopy was used for both stool DNA testing and FIT.

The sensitivity to detect colorectal cancer was significantly greater with stool DNA than with FIT (92.3% vs 73.8%; P = .002), as was the sensitivity to detect advanced precancerous lesions (42.4% vs 23.8%; P < .001).

Advanced precancerous lesion was the most advanced finding on colonoscopy for 757 patients (7.6%). Of these, 99 (13.1%) had a sessile serrated polyp at least 1 cm in size as the only advanced finding.

These lesions were proximally located in 79% of patients. The rate of occurrence was similar in women and men (48% vs 52%).

The prevalence of sessile serrated polyps was 9 per 1000 people in patients 50 to 64 years of age, 11 per 1000 in patients 65 to 74 years, and 4 per 1000 in patients 75 years and older.

High Sensitivity for Large Sessile Serrated Polyps

The sensitivity for the detection of sessile serrated polyps was significantly greater with stool DNA than with FIT testing (42.4% vs 5.1%; P < 0.001), but the specificity was lower (87% vs 95%; P < 0.001).

Sensitivity did not vary significantly for either test with respect to sex, age, or lesion location. Stool DNA detected more sessile serrated polyps in the proximal colon than FIT (38% vs 5%), and more in the distal colon (55% vs 5%).

 
It's remarkable that a noninvasive test has 93% sensitivity for cancer and is very good at detecting large precancerous lesions. Dr. Douglas Rex
 

The sensitivity of stool DNA increased as the size of the polyps increased — from 37% for polyps 1.0 to 1.4 cm, to 48% for polyps 1.5 to 1.9 cm, to 67% for polyps 2.0 cm and greater. In contrast, the sensitivity of FIT did not increase with increasing polyp size.

This analysis shows that sessile serrated polyps 1.0 cm and larger are uncommon, and comprise a minority of advanced precancerous lesions in asymptomatic people at average risk, Dr. Berger said.

"It's intriguing and exciting that the stool DNA test picks up these flat lesions that can be missed on colonoscopy," said session moderator Barbara Jung, MD, chief of gastroenterology and hepatology at the University of Illinois in Chicago.

"It's remarkable that a noninvasive test has 93% sensitivity for cancer and is very good at detecting large precancerous lesions," said Douglas Rex, MD, professor of medicine at the University of Indiana in Indianapolis.

"I don't think colonoscopy is off the map as a screening option. With FIT having more consistent results and fecal DNA having better results, we are wrestling with several legitimate strategies right now," he explained.

The cost of the test, which has yet to be announced, could be a factor in its uptake in clinical practice, especially for the healthcare system at large, he said.

Dr. Berger is an employee of Exact Sciences. Dr. Rex reports consulting for and being on the board of Exact Sciences. Dr. Jung has disclosed no relevant financial relationships.

Digestive Disease Week (DDW) 2014. Abstract 113. Presented May 4, 2014.

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