Joseph C. Anderson, MD: Adding mt-sDNA Tests to Colonoscopies

June 8, 2021
Kenny Walter

Using both tests to screen for colorectal cancer was more effective than just using colonoscopies alone.

New research shows a colonoscopy following a positive multi-target stool DNA (mt-sDNA) or fecal immunochemical test had a higher yield colorectal neoplasia when compared to colonoscopies alone. Although this finding is not unexpected, the research confirms this hypothesis and suggests the expected frequencies of those findings.

A team, led by Joseph C. Anderson, MD, Geisel School of Medicine at Dartmouth, Hanover Department of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center NH Colonoscopy Registry, investigated colonoscopy outcomes and quality after mt-sDNA and FIT screening tests in the population-based New Hampshire Colonoscopy Registry.Overall, positive mt-sDNA tests were significantly more likely to have colorectal cancer or advanced noncancerous neoplasia than the colonoscopy-only cohort.

Overall, positive mt-sDNA or FIT were significantly more likely to have colorectal cancer or advanced noncancerous neoplasia than the colonoscopy-only cohort.

In an interview with HCPLive®, Anderson explained how the results could impact cancer screenings moving forward, particularly for an older population.

HCPLive: Can you tell me what the main takeaway from this study?

Anderson: This study shows that the use of multi-target stool DNA screening tests can be helpful in enriching an average risk population that's attending colonoscopy so that when you perform the colonoscopy, you're more likely to do it for a purpose of preventing cancer, by finding polyps and removing them, because that's really how we prevent cancer.

We prevent colorectal cancer through the detection and removal of polyps. This study demonstrates that the use of multi-target stool DNA screening or fecal immunochemical tests can be useful in increasing the yield of findings at those colonoscopies.

And in particular, the multi-target stool DNA tests, because of the fact that they have the methylated markers, can be very useful in enriching the findings of serrated polyps at colonoscopy.

Other implications of the study are that we need more real-world data like this so that we can say what the expected yield of these tests should be in clinical practice.

An important quality measure is the adenoma detection rate or the percentage of screening exams performed by an endoscopist with at least one adenoma detected. When you do a colonoscopy in average risk individuals, what should you be finding in those individuals? Well, these data will help with understanding outcomes after the multi-target stool DNA test as well as FIT, to show what the frequency of colorectal neoplasia should be in colonoscopies of people who have positive tests.

HCPLive: How do you take the results of this study and implement it into the field so there is real-world clinical impact?

Anderson: The best way to do that is to publish it. We've submitted that on paper, so I think that's the best way to disseminate those findings. I think the message is two-fold. One is that we're providing benchmarks for the yield of positive tests when you do the follow-up colonoscopies. In other words, what you should expect to find. Adenoma detection rates are important because they tell you whether or not you as an endoscopist is doing a good job at finding important lesions.

The adenoma detection rate for colonoscopy certainly has gone up in the past several years. Studies seem to suggest that a reasonable rate for detecting adenomas at colonoscopy maybe in the 30s and if you're FIT positive, well, maybe that number might actually be 45. Our data suggest that 55 could be the number for multi-target stool DNA screening tests.

The other potential implication is that the higher frequency of findings after mt-sDNA appears to be due to higher yield of serrated polyps when you use the multi-target stool DNA test, because of the methylated markers that are present in mt-sDNA in addition to finding occult blood.

Take people who smoke for example. It's been shown that smoking is very much correlated with serrated polyps. Therefore, those individuals might have a higher yield if you use the multi-target stool DNA test. So those are some of the potential implications.

HCPLive: When talking about screening methods and different risk factors, how important is to continue to update the guidance over time?

Anderson: I think it’s very important. It’s an ever-changing field as the evidence evolves, so that makes it exciting to study. The tests themselves change and the ability of endoscopists to detect lesions changes as well. If you look at the data we and others presented in the past at other meetings, we have shown that serrated polyp detection has dramatically increased.

That's why I think these data are very timely and current and we hope to get them published in print in the next few months.

Detection of adenomas is important and technology and better technique has allowed for better detection. If you look at the adenoma detection rate, 20% was what was expected just several years ago. Now it's much higher, and now we expect people to get to 25%, and our data seems to suggest that 30% might be what a future benchmark may be.

HCPLive: In this sample of 52,000 individuals, the average age was 66.5. How concerning is it that the population is aging and we might be in a situation we’re going to have more patients with more serious illnesses?

Anderson: Some of my colleagues are working in this area, studying when do you recommend not screening or doing surveillance as a person ages, and there are tools that can be used to look at age expectancy, the patient's preferences, and what they've had previously. For people not at high risk a colonoscopy done last year gives you a lot of protection if it’s done with quality.

The other point is as people get older, if they are at average risk, alternative types of tests for screening might be beneficial in terms of not having to undergo colonoscopies. So multi-target stool-based tests are something that can be quite attractive with regards to identifying those average-risk individuals who could be identified through a positive stool test as needing a colonoscopy.

And certainly, as we get older, there are more serrated cancers. So something like the multi-target stool DNA based tests might be helpful in this older population.

HCPLive: Is there anything in this study that surprised you?

Anderson: I find these tests appealing because they’re biologically based. I do think that finding a difference in sensitivity seemed to make sense in terms of how the tests are structured, and the fact that there was a higher yield of serrated polyps in the multi-target stool DNA test is something that seems reasonable.

Thus, the study was important to shed more light on the areas we’ve discussed.


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