Two new DNA-based tests could noninvasively detect colon cancer, but it is unlikely they will replace CT colonography, according to experts. If anything, the tests could replace the fecal occult blood test currently in use.
In 1998, Dr. Joseph Ferrucci, considered the father of CT colonography and the interim chair of radiology at University of Massachusetts Memorial Medical in Worcester, predicted one day there would be a simple blood test for colon polyps.
“This is it,” he said in an interview with Diagnostic Imaging. “Though more clinical trials, in a broad range of environments, will likely be forthcoming.”
One of the tests was presented at the American Association for Cancer Research’s conference on Colorectal Cancer in Philadelphia on Thursday. The test uses a stool sample and works by detecting tumor-specific DNA alterations in cells shed into the stool from precancerous or cancerous lesions.
The first clinical validation included 1100 patients. Led by Dr. David Ahlquist, a professor of medicine and a consultant in gastroenterology at the Mayo Clinic in Rochester, MN, the researchers detected 64% of precancerous adenomas greater than 1 cm and 85% of cancers.
Colorectal cancer rate detection was 87% for cancers in stages I to III, and 69% in stage IV. More clinical trials are planned for next year, according to Exact Sciences, a molecular diagnostics company in Wisconsin that is developing the test.
“There is definitely an incentive and legitimate justification to be designing a screening approach that is user-friendly, affordable, and has the ability to detect precancers,” Ahlquist said. “The noninvasive stool DNA test we have developed is simple for patients, involves no diet or medication restrictions, no unpleasant bowel preparation, and no lost work time, as it can be done from home.”
Positive tests results would be followed up with colonoscopy, he said.
The other DNA-based test is in development by Epigenomics, a molecular diagnostics company based in Germany.
This test is derived from a blood sample and detects cell-free methylated DNA of the Septin9 gene shed into the bloodstream by colorectal tumors.
In the PRESEPT study, a prospective trial sponsored by Epigenomics with a cohort of almost 8000 patients, the blood test detected 67% of the colorectal cancer cases at a specificity of 88% when compared with colonoscopy.
Neither test will replace CT colonography, but if inexpensive, they could potentially be used to replace the fecal occult blood test/fecal immunochemical test currently in use, according to Dr. Judy Yee, a professor and vice chair of radiology and biomedical imaging at the University of California San Francisco and a CT colonography expert.
“The stool DNA methylation test is really in the category of colorectal cancer screening tests that screen for cancer, and does not do well for detecting the precursor adenomatous polyps, whereas CT colonography does significantly better for detecting the greater than 1-cm precursor polyps,” she said.
A 64% sensitivity for large lesions is too low. CT colonography does a significantly better job of detecting the larger lesions at a sensitivity of greater than 90%, she said.
Another CT colonography expert, Dr. Perry Pickhardt, a professor of radiology at the University of Wisconsin, Madison said sensitivity is still too low with stool DNA to get too excited.
“We will need to see how well it performs in actual clinical trials,” he said.
Ultimately these tests are a good thing because more people will get screened and then the positive results will be confirmed with a colonoscopy or CT colonography, Ferrucci said.
“These tests are not a bad thing for radiologists and an argument could be made that CT colonography volume would be increased, as many more patients are detected having positive tests and will require further investigation,” he said.
The added patient volume will ultimately exceed the colonoscopy capacity, Ferrucci said. In that scenario, CT colonography could be an ideal intermediate triage or filter test to select patients who really need colonoscopy for therapeutic removal of large or dangerous polyps and cancers.
