Advances in Colorectal Cancer Screening

In this interview, Dr. David Ahlquist, gastroenterologist and professor of medicine at the Mayo Clinic in Rochester in Minnesota, discusses early detection methods of colorectal cancer, touching on sigmoidoscopy, colonoscopies, fecal blood testing, and in particular, stool DNA screening.

David Ahlquist, MD, is a gastroenterologist and professor of medicine at the Mayo Clinic in Rochester, Minnesota. Dr. Ahlquist's research interests include the early detection of colorectal and other gastrointestinal neoplasms, and the development of new tools to screen patients for these neoplasms in a noninvasive manner.

Dr. Ahlquist is also involved in the identification of molecular markers in the stool and blood for better screening and detection of cancer and precancers. 

-Interviewed by Anna Azvolinsky, PhD

CancerNetwork: Colorectal cancer is a curable disease when detected early, which is why your research for better early detection tools is so important. Can you describe the types of early detection tools that are currently used?

Dr. Ahlquist: I will answer that question from a principle standpoint. Early detection is very important. I think one can argue that the best outcome would be to detect the precancers so that cancers can be prevented altogether. The downstream costs of taking care of colon cancer are enormous and the best outcome is to not to develop cancer in the first place. From a screening standpoint, that mandates detection of precancers. The ideal screening tool can detect not only the early-stage cancer but the precancers as well.

There are a number of screening arrows in our current quiver, and they all fall somewhat short of the mark, in terms of the ideal, in that some are expensive, invasive, they are not all accurate, and all of them are biased toward the detection of left-sided disease. They tend to miss right-sided lesions-even colonoscopies, based on recent, large population studies. As we currently do colonoscopies we miss some of the right-sided cancers and precancers which tend to be flatter and less conspicuous endoscopically. The other approaches are sigmoidoscopy-which looks at only the left colon, doesn’t look at the right colon-and fecal blood testing, which again detects more left-sided disease than right-sided, and tends not to detect precancers very well, because they tend not to bleed so much. So we don't have a perfect approach with our current armamentarium, and when one considers that more than half of all cancers occur on the right side-where our current tests are especially deficient-there is a continued need, an imperative, to reimagine how we do screening. Can we do it better?

CancerNetwork: I see. So could you describe the new developments, and specifically the stool DNA screening?

Dr. Ahlquist: Sure. I think there are a number of approaches that have been looked at. Different blood-based approaches and some technology, gizmology, like the swallowed video capsule and things. But it gets back down to the ideals. You want a noninvasive tool that is affordable, that detects lesions on both sides of the colon, precancers and cancers. So we started with the end in mind and looked at the ideal characteristics and asked if we can develop a tool that gets there. And we think that stool DNA comes very close to achieving the ideal. It is noninvasive. There is no bowel prep. It is very easy for patients. There are no diet or medication restrictions. They don’t have to miss work or daily activities and the sample can be sent through the mail. They don’t even have to go to the doctor or the healthcare center to be screened. The test is based on shedding of cells or exfoliation from the surface of cancer or precancers and we detect the DNA signatures in stool from those exfoliated cells to determine the presence of a cancer or polyps. With the new generation technical advances that are now possible, we have been able to generate extraordinarily high sensitivities for both cancers and precancers. We found that site within the colon makes no difference in terms of detection rates. Right-sided lesions are detected just as well as left-sided ones.

CancerNetwork: And so is this test currently in clinical trials? What stage of development is it in?

Dr. Ahlquist: Based on the very promising case-controlled data, the Mayo Clinic has been in partnership and collaboration with Exact Sciences, who are commercializing this test. Exact Sciences had worked with the FDA and with CMS to consider the downstream regulatory issues and they are actively involved now in a multicenter study to validate the performance of the test in the screen setting. It involves over 50 centers across the country. It should be done by the end of this year, 2012, and hopefully the FDA would approve it in early 2013.

CancerNetwork: That sounds great. So, interestingly, this topic is quite timely because the Center for Disease Control just issued a new federal study where they show that not enough people are getting screening for colorectal cancer among other cancers. And in fact, there is disparity in that Asian and Hispanic groups are even less likely to be screened. Do you think that this sort of DNA screening that is easier to use and less costly would allow for a broader patient population and even younger patients to be screened to not just to detect cancer, but to actually detect precancerous lesions and prevent cancer?

Dr. Ahlquist: The whole matter of participation rates and compliance, it is fairly complicated and there are many barriers to current screening approaches. Some of them are perceptive. Patients just don’t want to deal with discomfort, cost, time away from work, or with an invasive procedure. Geographically, they can’t always get to it, so access is an issue. With a test like this, access should not be a factor at all because the test goes where the mail goes, and the noninvasiveness and absence of any restrictions we hope will improve compliance rates substantially. Patients are consumers, as are physicians, and as it becomes more apparent that this is a test that works-it detects precancers and early stage cancers at very high rates-that also we hope will drive decision-making.

We know that effective screening can lead to cancer control very effectively. One needs only to look at the example of cervical cancer. Cervical cancer used to be the number one killer in women. Now with the cervical Pap smear it’s virtually been eliminated in terms of cause of death in regular screeners. This test detects precancer of the colon at higher rates than the cervical Pap smear does in the cervix. So it is our hope and our ultimate goal to have a test like this broadly used and to be a big step in eradicating colon cancer just like Pap smears have done for cervical cancer.

CancerNetwork: Well that sounds like very good news. Thank you so much for joining us Dr. Ahlquist.

Dr. Ahlquist: Thank you for your interest.