Results of two studies suggest that a new, investigational colorectal cancer screening test developed in collaboration between Mayo Clinic in Rochester, Minn., and Exact Sciences of Madison, Wis., is highly accurate and significantly more sensitive than other noninvasive tests at detecting precancerous tumors and early-stage cancer, according to a statement issued Jan. 18 by Mayo Clinic.

The first large-scale, blinded study, to be published in the February issue of Gastroenterology, showed that the multi-marker stool DNA test is highly accurate at detecting precancerous polyps and early-stage colorectal cancer.

The second study, to be published in the March issue of Clinical Gastroenterology and Hepatology, showed that the stool DNA test is significantly more accurate than a new plasma test for identifying patients with large precancerous polyps or colorectal cancer, while delivering fewer false-positive results.

Although colorectal cancer screening is recommended for everyone beginning at age 50, 60 percent of patients are diagnosed with the disease in its late stages, primarily due to poor screening compliance.

"Our findings in these studies underscore the great potential of the stool DNA test as a colorectal cancer screening tool," said David A. Ahlquist, MD, of Mayo Clinic, principal investigator of both studies, in the statement. "Along with its high accuracy, this test approach could improve participation rates due to its patient-friendly features."

The DNA stool test works by finding signature genetic markers in stool samples mailed in by patients. A positive test would be followed by a colonoscopy to remove the polyps and prevent a subsequent cancer from forming.

What does it mean for CT colonography?
“Both tests show high accuracy, but CT colonography is much more expensive, involves a bowel preparation and time away from daily activities, and is associated with a radiation exposure risk. As such, the role for CT colonography for colorectal cancer screening at the population level has not yet been endorsed by professional societies (like American Cancer Society [ACS]) and is not approved by Medicare or FDA for this application,” according to a Mayo Clinic blog posting.

“On the other hand, stool DNA testing has already been endorsed by many professional societies, including the ACS, and approvals by both FDA and the Centers for Medicare & Medicaid Services are in process. The test is much less costly, involves no prep or diet/medication restrictions, and can conveniently be done via mail,” wrote Mayo on its blog.

“It will be patient choice, market forces and regulatory approvals that will determine which test is most widely used for population screening,” Ahlquist said in an interview with Health Imaging.

Ahlquist said CT colonography could be used in a complementary role with the stool DNA test. For example, CT colonography might provide a good alternative for patients at high-risk for disease or those with a positive stool test who are not good candidates for colonoscopy. In addition, CT colonography becomes a more attractive test when it examines the abdomen beyond the colon—ovaries, liver, pancreas—or it includes bone density measurements, Ahlquist told Health Imaging.

Ahlquist and colleagues also are examining studies to generate evidence to guide the decision-making process in cases when stool DNA results require evaluation of the upper gastrointestinal tract. “There will likely be radiographic tools to examine the pancreas and upper GI tract,” said Ahlquist.

The study to be published in Gastroenterology examined nearly 400 cases and the stool DNA test detected 87 percent of curable-stage colorectal cancer. Detection sensitivity was not affected by tumor location or stage.

The test detected the majority of large precancerous polyps at high risk for cancer progression. Sensitivity was 64 percent for polyps larger than 1 cm, 77 percent for those larger than 2 cm and 92 percent for those larger than 4 cm.

"These data illustrate the strength of the multi-marker stool DNA test to the critical screening targets—pre-cancers and early-stage cancer," said Stephen N. Thibodeau, PhD, a genetics researcher at Mayo Clinic, in the statement. "And, importantly, this test appears to uniquely represent an accurate noninvasive approach to large polyp detection, which offers the promise of actually preventing cancers from developing."

The study to be published in Clinical Gastroenterology and Hepatology used the results of the first study to compare the sensitivities of the stool DNA test and a plasma test for methylated Septin 9 (SEPT9) in identifying patients with large adenomas or colorectal cancer. Highlights included:

• The stool DNA test detected 82 percent of precancerous polyps compared with only 14 percent detected by SEPT9.
• The stool DNA identified 87 percent of cancers at any stage, compared with 60 percent with SEPT9.
• Stool DNA was more effective at detecting curable-stage cancer (Stage I, II or III), detecting such cases 91 percent of the time, compared to 50 percent with SEPT9.
• The SEPT9's rate of false-positives was nearly four times that of stool DNA (27 percent vs. 7 percent).

The multicenter validation study for FDA approval should be completed by the end of 2012, and the test (if approved) could become available as of 2013.