Large Study Shows Stool DNA Testing for Colorectal Cancer has Potential, but Challenges Remain

The first generation of a stool DNA test to identify early colorectal cancer has limitations, according to a Mayo Clinic-led study published in the Oct. 7, 2008, issue of Annals of Internal Medicine. Results did not corroborate findings of an earlier multicenter study that showed stool DNA testing was more accurate than fecal blood testing for colorectal cancer detection. *

“But the concerns we identified with stool DNA testing are all solvable,” says David Ahlquist, M.D., lead researcher in the study that included 4,482 participants and 22 academic medical centers. Researchers have hoped that stool DNA testing could be the user-friendly and accurate screening tool that would increase screening numbers.

More than half of adults in the United States have never been screened for colorectal cancer, the second-leading cause of cancer deaths. While available screening tools work, the most effective tests involve time, effort and costs. For example, colonoscopy requires fasting, bowel cleansing, a physician visit, sedation, an invasive procedure and lost work time - factors that contribute to low screening participation.

This blinded study, conducted from 2001 to 2007, compared screening effectiveness of two widely used fecal blood tests (Hemoccult and HemoccultSensa) with a stool DNA test in average-risk patients, ages 50 to 80. The DNA test used was the prototype for PreGenPlus, the first commercially-used stool DNA test, and was performed on samples sent to EXACT Sciences in Marlborough, Mass. All participants underwent a colonoscopy, the gold standard in current screening. Researchers used colonoscopy as the benchmark to detect cancer or precancerous polyps.

In the fecal blood screening, lab technicians searched for unseen traces of blood from stool that patients smeared onto a card. The presence of blood might indicate colorectal cancer. However, tumors bleed intermittently, which limits the test’s accuracy for cancer detection. Three stool samples were tested for blood for each participant, the typical approach for fecal blood screening.

In DNA testing, researchers used sensitive laboratory tools to identify DNA from cells shed from cancer and precancerous polyps in stool samples. Only one sample was required because DNA shedding is believed to be continuous.

At about the study’s halfway point, when 2,497 patients had been tested, researchers compiled an interim analysis. “All stool tests performed suboptimally,” says Dr. Ahlquist. “The stool DNA test detected 20 percent of cancer and precancerous polyps, compared to 11 percent by Hemoccult and 20 percent by HemoccultSensa.”

“We didn’t think that stool DNA test performance was good enough to justify continuing without some changes,” he says. Dr. Ahlquist and colleagues switched to a second-generation DNA test with improvements including a better method to capture DNA from stool and a more accurate panel of DNA markers.