Ask AI
Back Back
The Evolution of Colorectal Cancer Screening: A Candid Conversation with Paul Limburg, MD, MPH
Activity Information Ask a Question

Activity

Progress
1
Course Completed
Activity Information

Released: August 26, 2026

John Marshall
John Marshall, MD
Catch Up On All Episodes of Oncology Unscripted

Watch Now

The Evolution of Colorectal Cancer Screening: A Candid Conversation With Paul Limburg, MD, MPH

John Marshall, MD: Good day, everybody. John Marshall for Oncology Unscripted, and as promised, we have a world's expert in the realm of screening for cancers, GI cancers in particular. And this particular individual has expertise from, if you will, both ends: the old-fashioned end of putting a scope up one end and the new-fashioned end of being able to detect early-stage or maybe even premalignant disease through blood testing. And we are very honored to be joined by Dr. Paul Limburg. And I'll let Paul do his own self-introduction, a little bit about where he came from and how he ended up in the spot he is now. Paul, take it away.

Paul Limburg, MD, MPH: Yeah. Thanks, Dr. Marshall. I appreciate the opportunity. I am a gastroenterologist. I did all of my training at Mayo Clinic, except for a fellowship in preventive oncology at the National Cancer Institute. I spent 25 years working at Mayo Clinic in Rochester, Minnesota, on the GI faculty with a focus on cancer prevention, GI and otherwise, and also health and wellness.

So, really trying to understand human behaviors, trying to keep people out of the doctor's office, if you will. And through that journey, I had the privilege of meeting with another colleague named Dave Ahlquist. Dave was one of the co-inventors of a test called Cologuard and a company called Exact Sciences that delivers Cologuard to the clinicians.

And through that process and through three decades of working together, I ended up joining Exact Sciences after retiring from Mayo. Just one more piece to the story, at least so far: Abbott has acquired Exact Sciences, so now the maker of Cologuard is Abbott Cancer Diagnostics.

John Marshall, MD: You had me once you had a golf tournament, just to be honest. So I thought, you know, how do I get a job with you guys and maybe go work? Have you been to the golf tournament?

Paul Limburg, MD, MPH: Absolutely. It is a wonderful event, and one way to think of it is a chance to bring advocacy organizations, patients, caregivers, and survivors all together, with a golf tournament thrown in.

John Marshall, MD: And I know you've been very supportive of the Colorectal Cancer Alliance and their work that they're doing. So, in disclosure from my side, I also have a strong partnership with the Colorectal Cancer Alliance that crosses over at the golf tournament and other activities with Exact and the like. So first off, Paul, thank you so much for giving us your valuable time. We might circle back to prevention if we have a little time at the end, but kind of with me a little bit. I mean, we've been having these, you know, blood tests. You were saying you started off with stool tests, which has been the standard. It evolved to colonoscopy, to really set our timeline here, then the fancier tests all the way up to Cologuard, and now blood tests looking for cancer. Maybe, in your sort of evolution—and you lived through a lot of that evolution—tell us a little bit about why we've headed this direction.

Paul Limburg, MD, MPH: The timeline is really interesting. You know, it's certainly been in my career that we've seen a lot of the changes that you mentioned, John, and really it's only been about 25 or 30 years, maybe a little bit longer, that colorectal cancer screening has been endorsed by national guidelines.

So we do know from all of the research that's been conducted, you know, several pivotal studies published in leading medical journals have shown that colorectal cancer is a highly preventable condition, and the best way to do that, or at least a very effective way to do that, is with colorectal cancer screening of asymptomatic individuals.

So, as we think about how we could do that, stool tests, as you mentioned, have been around for a long time, typically or historically only measuring fecal occult blood, in some ways not using, you know, the most accurate technology to do that with a single marker.

Colonoscopy is something that's a little bit newer, and in the early 2000s, when national celebrity Katie Couric had her live televised colonoscopy, I think that raised additional interest in: how can I get screened? When should I get screened? Et cetera. You mentioned fecal immunochemical testing as a next step in the stool screening process.

And then, in 2014, Cologuard came to the clinic, and that is a molecularly based stool screening test that combines DNA methylation, DNA mutation, and fecal hemoglobin using the ELISA technology that is also applied to most FIT tests. So this multi-panel, molecularly based stool test can really, um, help to identify patients who have cancers and precancers and has been used to screen over 20 million times during the last decade-plus.

John Marshall, MD: Yeah, let me jump in here a little bit. When I think about screening, you know, one of the basic rules is it needs to be inexpensive, noninvasive, high sensitivity and specificity, and all those things. And I realize we bend those rules because of the importance of early detection and the like. The other piece of this is colonoscopy, specifically. I always think of that as something you do every now and then because you're hunting polyps, and if we believe Bert Vogelstein and the whole biology around polyp formation, then you don't need to do it that often because you'll find it somewhere in between there. As I've been a GI oncologist for a thousand years now, I recognize that there's a lot of colon cancer that doesn't start with a polyp, and certainly we now have this problem of young-onset colon cancer, which may or may not be from a polyp too.

So I'm thinking about the newer tests, the genetic tests, for example, actually are also in keeping with the increased understanding that there's a broader biology than just a polyp and finding it early. Are you all aligned with that? Does that make sense, or am I off base there?

Paul Limburg, MD, MPH: No, that makes perfect sense. I think one key learning for me over the years is that colorectal cancer is not a single disease. And I think that's what you were alluding to, John. So, you know, there are different pathways of carcinogenesis. We know about the consensus molecular phenotypes, et cetera, et cetera.

But if we think of colorectal cancer as more than a single-pathway disorder, and if we think actually of the disease as carcinogenesis rather than the endpoint of colorectal cancer, then we can really position our innovations toward disrupting that process of carcinogenesis at the earliest possible point, ideally at the preinvasive stage.

John Marshall, MD: To that point, I think a lot of people, docs as well as the public, of course, see, you know, colonoscopy as sort of a one-and-done: I can wait 5 to 10 years. Whereas I'm not sure we've been as good, me included, in the messaging that if you're gonna do fecal testing or maybe the evolution to blood testing, it's not so much a one-and-done.

You have to do this more on a regular basis, sort of like our friends over in mammography. You don't just do it and then don't do one for 10 years. You kind of keep a track record. Is that where we need to be messaging?

Paul Limburg, MD, MPH: Definitely. And it starts with: colorectal cancer screening is effective. Number two is that it's not one-size-fits-all. So there are different attributes of every colorectal cancer screening strategy, and clinicians and patients need to be aware of what those key elements are with any test or strategy so that they can determine what's most important to me: having to go into a doctor's office or not, having to repeat the test every 10 years, every 3 years, every 1 year, accuracy of the test, access to the test. All of those are important considerations.

John Marshall, MD: Yeah, I think it's really important for us to beat that drum, and I think the more recent, you know, exciting news about blood testing being sort of accepted or increasingly accepted—and I know everyone's pushing in that direction—you know, the headlines read, you know, screening now can be a blood test. But without that sort of emphasis on the serial nature of a blood test, sort of it's not replacing colonoscopy but is an alternative to it, with its own pathway.

Is that fair?

Paul Limburg, MD, MPH: It is fair. And, going back to what the goals of screening are at a programmatic level, with colorectal cancer, we have the unique opportunity both for early detection and prevention by finding those precancerous polyps or lesions and effectively taking them out through a colonoscopy, for example.

But there are tests that are recommended for screening that are better at finding cancers and precancers, tests like colonoscopy. Even Cologuard is FDA-approved for that indication, versus some other tests like blood tests, which are designed or approved to detect cancers but have lesser ability to detect even the early-stage cancers or the preinvasive lesions, the polyps that can arise and hopefully be removed before invasion.

John Marshall, MD: Yeah. Let's drill on that because that's what the talk is in the doctor's lounge: that with the blood test, you have to have invasive cancer because the blood tests aren't good enough, or they shouldn't, in theory, pick up something that is noninvasive on some level. At least the stool test could, but the blood test could not. So what's your take on that? Where do you think that's going to evolve?

Paul Limburg, MD, MPH: Yeah. We're really excited about the simple screen, uh, CRC test, which, full disclosure, Abbott Cancer Diagnostics has a license to bring to the clinic. And it definitely has a supportive evidence base that shows that the test can detect cancers, and it detects relatively fewer precancers.

So the ability to identify the DNA markers in the bloodstream, I think, is predicated on the biology of the process. So if you think about a precancer that has not broken through its tissue boundaries, it would be conceivable, biologically plausible, that it would be difficult—more difficult—to find those markers in the bloodstream.

With more advanced-stage cancers, obviously, that ability to invade and be part of the peripheral circulation should go up, and so the tests perform better with those more advanced-stage cancers. But there is a key point, John, and that is that blood-based colorectal cancer screening is better than no screening at all.

And we know that there are 60 million people thereabouts who are unscreened or underscreened, meaning that they're not up to date with guideline recommendations. And so, finding a test like a blood test—if somebody's not willing or able to have another endorsed strategy like colonoscopy or a stool test like Cologuard, now Cologuard Plus—is better than no screening at all.

John Marshall, MD: Put me out of business. That is your job, to put me out of business, and I wouldn't mind that, uh, if we could succeed at that. But to that end, you saw—and pointed out this to our audience—the paper about... it was done in India, where access to things is not quite as great, but they trained these dogs to actually sniff in people and were pretty good at predicting.

You know, we've talked on this program about AI looking at digital pathology to predict outcomes. So there are other ways to measure or to detect that are beyond our immediate senses, and what these genetic tests are is one of those, uh, arms. So, uh, is there any concern? Should Abbott start looking into, like, some Purina Dog Chow kind of market as well?

Paul Limburg, MD, MPH: We're always innovating. So, wherever we think we can advance the mission, we truly are about trying to reduce the cancer burden, colorectal and other cancers, as best we can. We always use that patient-centric approach. We are now the only group that can provide both a guideline-endorsed stool test and an FDA-approved blood test to try to meet patients where they are so that we can more effectively get patients screened and hopefully avoid, uh, the consequences of a highly preventable condition like colorectal cancer.

John Marshall, MD: Yeah, thank you. Let me close with a sort of different kind of question. Back to your days of prevention—you're still in those days, I assume. You know, my favorite paper before the dog paper was, in fact, the exercise paper, where, uh, after stage III colon cancer, patients were randomized to a pamphlet telling them to go exercise versus a personal trainer. You may know those data, that 8% difference in cure rate with a personal trainer. Then I think about the obesity epidemic, its linkage to colon cancer, and I think about the new, uh, uh, obesity drugs that are out there that everybody's taking, and you start to hear through Twitter that these things might be, you know, helping with cancer and the like. What's your take as a prevention expert on this exercise, obesity, maybe, uh, you know, control as a way to help reduce the incidence of colon cancer?

Paul Limburg, MD, MPH: Yeah, maybe just the simplest way to frame it in this context is: what's good for your overall health is good for your colon health. So maintaining a healthy diet, watching what you eat, avoiding some harmful exposures like, uh, tobacco and alcohol in excess, exercise rather than sedentary behavior—all of those things are good for people in general, and they also have been shown in most studies to be beneficial with respect to reducing colon cancer risk.

John Marshall, MD: I lied. I got one more question. So I'm obsessed with the microbiome. I have no idea how to measure it. All of these young people with new young-onset colon cancer have rectosigmoid primaries. There's something going on there. When I was a kid, there was no such thing as peanut allergies or IBD, and now... So something's going on there, and you are actually increasingly collecting stool samples. Uh, by the time they make it to you, are they usable for analysis? Is there stuff that we can be doing with those specimens to learn from?

Paul Limburg, MD, MPH: It's a great point. So I think we've only scratched the surface with our understanding of the microbiome and its association with disease states both inside and beyond the GI tract. So, to your question, yes, Abbott collects stool samples every day as part of the Cologuard specimen return process.

We've done some early testing to look to see: can we measure and characterize the microbiome from those samples? Short answer is we can. The longer question, and where there still needs to be more research, is: what can we do with that information that has real clinical value?

John Marshall, MD: Dr. Paul Limburg, thank you so much for joining us here today. Um, it's really been an honor to talk with you, and I know all of our listeners learned a ton. I know I did. So, Paul, thanks very much for joining us.

Paul Limburg, MD, MPH: My pleasure. Thank you.

This transcript was generated by AI and lightly edited.