IU, Regenstrief study: New noninvasive colorectal cancer screening tool highly accurate

INDIANAPOLIS -- An Indiana University and Regenstrief Institute study of nearly 10,000 average-risk, asymptomatic men and women from 90 sites across the United States reports that a multi-target stool DNA test -- a new noninvasive colorectal cancer screening tool that has not yet been approved for sale by the Food and Drug Administration -- detects 92.3 percent of colon cancers, compared to only 73.8 percent of cancers detected by a fecal immunochemical test, the most commonly used noninvasive test today.

Study results were published online March 19 and in the April 3 print issue of the New England Journal of Medicine.

Approximately nine out of 10 Americans older than 50 are thought to be at average risk for colon cancer. Sensitivity -- the ability of a test to detect disease -- is the most important characteristic for cancer screening tests because their primary role is to "rule out" disease.

The multi-target stool DNA analysis is conducted on a single stool sample expelled from the body directly into a container and mailed to a laboratory. The new test, which looks for human DNA mutations present in the stool as well as fecal blood, identified a significantly higher number of colorectal cancers compared to the current standard noninvasive method: fecal immunochemical test, or FIT. The study found that FIT identified 73.8 percent of colon cancers, about 20 percent fewer than the new multi-target stool DNA test. Colonoscopy, which is presumed to find all colon cancers, was the "gold standard" used as the reference method in the study.

The multi-target stool DNA test's ability to identify cancer did not vary in a statistically significant way by either cancer stage or location within the colon.

"While screening has been shown to reduce both the occurrence of and death rates from colorectal cancer, not enough people get screened," said lead author Thomas F. Imperiale, M.D., of the Indiana University School of Medicine, Regenstrief Institute Inc., the IU Simon Cancer Center, and the Roudebush VA Medical Center in Indianapolis, which was one of the recruitment sites. "If approved by the FDA, this noninvasive option may encourage some of those who currently avoid screening to get tested."

In addition to identifying nearly all cancers, multi-target stool DNA identified the most worrisome of advanced precancerous polyps -- those that were two centimeters or larger and those containing high-grade dysplasia -- nearly 70 percent of the time, compared with approximately 45 percent of the time for FIT.

While the multi-target stool DNA test detected significantly more cancers than did FIT, the study also found that the new test produced more false positive results than FIT.

"All screening tests for low-prevalence conditions such as cancers, which include mammography for breast cancer, Pap smears for cervical cancer, and PSA tests for prostate cancer, will have more false-positive test results than true-positive test results," said Dr. Imperiale.

Study participants ranged in age from 50 to 85. Each was screened by colonoscopy and FIT in addition to the multi-target DNA test.

"The multi-target stool DNA test could provide another non-invasive option for colorectal cancer screening if it is approved by the FDA. While our study provides high-quality information about test performance of this new technology and demonstrated superior sensitivity to FIT, it does not indicate which test is "best" for a particular patient, said Dr. Imperiale. "There are tradeoffs with each screening test. Physician and patient should decide together which test works best for the patient based on a variety of factors including risk of disease, risk of false-positive and false-negative test results, tolerance for the preparation process for colonoscopy and the procedure itself, as well as likelihood that the patient will complete the chosen screening test."

The National Cancer Institute reports that colorectal cancer is the second leading cause of death from cancer in the United States. According to the Centers for Disease Control, at least 60 percent of deaths from colorectal cancer could be avoided if all individuals age 50 and older were screened. About 90 percent of people live five or more years when their colorectal cancer is found early through testing, according to the CDC.

In addition to lead author Dr. Imperiale, co-authors of the study are David F. Ransohoff, M.D., of the University of North Carolina at Chapel Hill; Steven H. Itzkowitz, M.D., of the Icahn School of Medicine at Mount Sinai; Theodore R. Levin, M.D., of Kaiser Permanente Medical Center, Walnut Creek, Calif.; Philip Lavin, Ph.D., of the Boston Biostatistics Research Foundation; Graham P. Lidgard, Ph.D., and Barry M. Berger, M.D., of Exact Sciences Corp.; and David A. Ahlquist of the Mayo Clinic.

The study was funded by grants from Exact Sciences Corp. of Madison, Wis., manufacturer of the multi-target stool DNA screening test.

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