Conference Coverage

Alternatives to colonoscopy for CRC screening are works in progress




SAN FRANCISCO – Colonoscopy may be the most commonly used technique to screen for colorectal cancer in the United States, but it’s far from perfect, according to Dr. David A. Lieberman.

For one thing, serious complications occur in 3-5 per 1,000 procedures at 30 days of follow-up, “and if you look at individuals over 65, the rates almost double in terms of serious complications,” Dr. Lieberman, chief of the division of gastroenterology and hepatology at Oregon Health and Science University, said at the 2015 AGA Tech Summit, which is sponsored by the AGA Center for GI Innovation and Technology. “The rate of perforation over age 65 is about 1 per 1,000,” he said.

Colonoscopy is invasive, “and it would never be conceived of as the ideal test for population-based screening,” he added. “It’s expensive, and [clinicians] in many countries simply do not have the resources and expertise to do it.”

Compared with current screening rates in the United States for cervical and breast cancer, a “screening gap” exists in the percentage of adults who are up to date in tests for colorectal cancer, he said. “If you look at what’s been accomplished with cervical cancer screening and mammography, we see that there’s a ways to go for colonoscopy,” he said.

The ideal screening test for colorectal cancer would accurately identify individuals at risk for colon cancer at an early, preventable stage, Dr. Lieberman said. That prevention element “really averts the downstream colon cancer care costs, which would be very attractive in a single-payer health care system,” he said. “If we had a system that took care of us for life, that system would be very invested in trying to prevent colon cancer, because [it would] be worried about those downstream costs.”

One potential alternative to colonoscopy is fecal immunochemical testing (FIT). A recent meta-analysis suggested that FIT detected cancer with a 79% sensitivity (Ann. Intern. Med. 2014;160:171-81), and a separate, recent prospective study found a 74% sensitivity rate in detecting cancer, but a 24% sensitivity rate in detecting advanced adenoma (N. Engl. J. Med. 2014;370:1287-97). “So in terms of early detection, FIT is pretty good,” Dr. Lieberman said. “In terms of cancer prevention? Maybe not so good. There are also issues around the testing program, which requires adherence to both positive and negative tests. Some of these behavioral factors play a major role in the actual effectiveness. So you can have a great test, but if it’s not getting done properly then there’s going to be an issue. There is some potential for CRC prevention, but it’s going to be less than for some others.”

What about stool DNA? A landmark study found that stool DNA detected cancer with a sensitivity of 92%, compared with FIT at 74% (N. Engl. J Med. 2014;370:1287-97). However, the sensitivity for detecting adenomas was relatively low for both methods (42% for stool DNA, compared with 24% for FIT). Stool DNA testing “appears to be an effective screening test [but] the appropriate interval for testing is still uncertain,” Dr. Lieberman said. “The recommendation is a 3-year interval.”

He characterized serum testing as the “holy grail” of screening for colorectal cancer, “because it would be ideal to have a noninvasive test. You’d come in, get a blood draw, and get risk stratified. There are a number of different possible pathways, one looking at specific genetic markers, others looking at genetic fingerprinting: in other words, seeing a pattern of genes that are associated with colon cancer versus patients who do not have colon cancer. Proteomics is another fingerprinting technique, as is metabolomics: looking at a variety of metabolites that may be altered by the presence of having neoplasia. This is an intriguing area but so far there hasn’t been a lot of data.”

To date, the most progress involved in this area involves molecular tests of DNA or proteins. “These studies are all relatively small and somewhat promising in terms of cancer sensitivity, but not so great for adenoma sensitivity,” he said. “It’s fair to say that this is still a work in progress.”

Dr. Lieberman reported having served on the scientific advisory board of Exact Sciences.

In a separate presentation, Dr. Uri Ladabaum updated attendees on the status of PillCam, also known as colon capsule endoscopy (CCE), for detecting colon cancer. The PillCam is cleared by the Food and Drug Administration for detection of colon polyps in patients after an incomplete optical colonoscopy with adequate preparation, or if a complete evaluation of the colon was not technically possible. In a large meta-analysis, the first-generation PillCam achieved a sensitivity of 71% and a specificity of 75% in detecting polyps of any size and a sensitivity of 68% and a specificity of 82% in detecting polyps 6 mm in size or larger (Clin. Gastroenterol. Hepatol. 2010;8:515-22). “The results were somewhat disappointing for a test like this, not hitting the bar that we would want,” said Dr. Ladabaum, professor of medicine in the division of gastroenterology and hepatology at Stanford (Calif.) University.


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