Novel Stool DNA Test May Enhance Colon Cancer Screening

24-03-2014 14:05

An investigational multitarget stool DNA test for screening colorectal cancer detects significantly more cancers than the currently available fecal immunochemical test (FIT), researchers report.

But it does so at the cost of more false-positive results.

"This new test is the most sensitive noninvasive test for detecting colorectal cancer," said lead study author Thomas F. Imperiale, professor of medicine at the Indiana University School of Medicine in Indianapolis.

The advantages are that it could be done less frequently than annually. We are going to have to have computer simulation analyses tell us what an appropriate interval would be," he told Medscape Medical News in a telephone interview.

"The new test is very good at detecting curable-stage cancers. If there is a downside, it's that the specificity is not as good as FIT. That's the way it goes with diagnostic tests. The more sensitive they are, usually the less specific they are," he said.

The study was published online March 19 in the New England Journal of Medicine.

The test, known as Cologuard, is produced by Exact Sciences and was codeveloped by the Mayo Clinic. It consists of quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and β-actin, plus a hemoglobin immunoassay. The test is currently under review at the US Food and Drug Administration; the company is scheduled to appear before the Molecular and Clinical Genetics Panel of the Medical Advisory Committee on March 27.

Noninvasive Alternative to Colonoscopy

Despite widespread recommendations and the availability of several screening tests, a substantial proportion of the American population does not get screened. The noninvasive nature of this stool DNA test might make colorectal cancer screening more acceptable, Dr. Imperiale said.

He and his team evaluated 9989 asymptomatic people 50 to 84 years of age who were considered to be at average risk for colorectal cancer and who were scheduled to undergo a screening colonoscopy.

All participants provided a stool specimen before routine bowel preparation for colonoscopy.

On colonoscopy, colorectal cancer was identified in 65 participants — a prevalence of 0.7%. Of these, 60 had stage I to III cancers. In addition, advanced precancerous lesions were identified in 757 (7.6%) participants.

Stool DNA testing identified 60 of the 65 participants with cancer, for a sensitivity of 92.3%, including 56 of the 60 participants with stage I to III cancers, for a sensitivity of 93.3%.

DNA testing sensitivity did not vary significantly by cancer stage or location in the colon, Dr. Imperiale reported.

DNA testing also identified 321 of the 757 advanced precancerous lesions, 27 of the 39 (69.2%) participants with high-grade dysplasia, and 42 of the 99 (42.4%) participants with sessile serrated polyps 1 cm or larger.

The sensitivity of the DNA test increased as lesion size increased, and was higher for distal advanced precancerous lesions than for proximal lesions (54.5% vs 33.2%).

Age did not affect its sensitivity for detecting cancer.

For the 9167 participants who had colonoscopy findings other than colorectal cancer or advanced precancerous lesions, such as nonadvanced adenomas or negative results, the specificity of the DNA test was 86.6%.

For the 4457 participants with negative colonoscopy results, the specificity of the DNA test was 89.8%. In this subgroup, specificity was 94.0% for participants younger than 65 years and 87.1% for those 65 years and older.

For colorectal cancer, overall sensitivity was significantly better with DNA testing than with FIT (92.3% vs 73.8%; P = .002).