Published on Jun 04, 2021

Video Transcript

[MUSIC PLAYING] JOHN WHYTE: Hi, everyone. I'm Dr. John Whyte, chief medical officer at WebMD, and you're watching Cancer in Context, where we really try to put into perspective some of the latest advances in cancer prevention and screening and treatment. And today, I want to talk about how screening has changed in general and colorectal cancer screening in particular.

So to help provide some insights, I've asked Dr. Paul Limburg. He's a gastroenterologist at Mayo Clinic and the chief medical officer of screening at Exact Sciences. Paul, Thanks for joining me today.

PAUL LIMBURG: John, good to be with you. Thanks for having me.

JOHN WHYTE: We chatted a little while ago. And I'm really interested in how screening has changed even over just the last few years. And I want to talk about in those diseases where now we're actually looking for cells, precancerous cells, genetic material in terms of screening. How does that change the screening process?

PAUL LIMBURG: I think dramatically, John. So since 1970, there has been a substantial decline in the colorectal cancer death rate, which is largely attributable to increased awareness and adoption of colorectal cancer screening. Now back in the '70s, '80s, even into the '90s, there were fewer options available for colorectal cancer screening.

Patients could check their stool for blood if they had access, and if they could afford to have a procedure like a colonoscopy, that was also possible. But since the 2000s, there had been many more options. And as you point out, we've gone from, I would say, more of a general approach to more of a molecularly driven approach, including now the ability since 2014 to do a stool test, for example, to look for molecular markers associated with colorectal cancers and precancers.

JOHN WHYTE: Let's talk about how that works without giving a whole immunology and molecular biology lesson. What does this technology doing and what is it looking for?

PAUL LIMBURG: When you think about how tumor cells are shed from a cancer or even a precancer, they are exfoliated from the surface primarily. Now that becomes mixed in with the debris in the stool, for example. And based on evolution of technology, that DNA, those DNA fragments can be isolated, separated from bacterial DNA, other human DNA from a stool sample and then interrogated to find the markers that have been associated with those lesions of interest. So for example, the multitarget stool DNA test that is now commercially available looks for 10 molecular markers and a hemoglobin marker as a strategy to screen average risk patients for colorectal cancer.

JOHN WHYTE: So we're really actually looking at DNA, perhaps, of precancerous cells and isolating them. I like how you used interrogate it. Some people might think we're questioning them. But in a way, we're doing this analysis.

Now this type of technology doesn't exist currently for all types of cancers. Correct it. I mean, we're studying it in other areas, but primarily, the advancements have been made in colorectal cancer. Is that correct?

PAUL LIMBURG: I think that's fair. There have been tremendous advances in multiple different areas. And I think that the future of cancer screening in general is very promising. There are also technologies that are evolving that may allow us to use different sample types, a blood sample for example, to screen for more than one cancer with a single specimen rather than trying to screen for each specific cancer individually.

JOHN WHYTE: And where we've seen in blood tests primarily has been in people that we already know have cancer and are perhaps looking to see what could be the markers or perhaps what chemotherapeutic agents might be most effective in them. But it would be a big jump to be able to do a blood test to look for cancer. But I want to ask you, Paul. We always talk about cancer.

We use it almost as this singular noun, but it's really a range of different diseases. Do you really expect that at some point, we'll be able to have a blood test to detect all types of cancer? What's your crystal ball telling you?

PAUL LIMBURG: One of the most important questions and challenges for the field, John. So to me, the target that we're after is actually carcinogenesis, so the process where a cell goes from normal to abnormal and invasive meeting the definition for cancer. That has some commonalities across different body parts, but you're right. There are definitely differences in which markers, which genes might be relevant to one cancer or another. So the goal with a blood test or a liquid biopsy, if you will, is to find where are those markers, what is that smallest number of markers that gives us information about the different cancers of interest, but doesn't create a high number of false positive results so that patients are anxious about the findings from a blood test and would have to undergo diagnostic testing that they may not otherwise need.

JOHN WHYTE: How many years away do you think that is?

PAUL LIMBURG: It's a bit hard to predict, but the encouraging news is that there are already groups out there that have developed early stages of these liquid biopsy assays, these multicancer early detection tests. And those are in late stages of development and some are even entering into clinical settings already.

JOHN WHYTE: I want to go back to colorectal screening, and as you know, I still see patients. And I've joked with you that the colonoscopy is always the appointment where there is a lot of no shows. And patients always will be like, oh, I didn't have someone to drive me, oh, I forgot, or that they really just could not tolerate the prep, that requirement to clean out your colon before you can undergo the procedure. And really screening has evolved in some ways.

How do we make it more convenient to patients? How do we make it more comfortable in a way? Some of the procedures that we do throughout screening can be a bit uncomfortable to patients. Sometimes we ask them to disrobe in terms of skin cancer.

One of the things that COVID has taught us is that if people can do things in their home, that they may be more likely to do a test. And we really have seen advancements in terms of colorectal screening in a test that patients can do at the home. So let's talk about that and why that's so important.

PAUL LIMBURG: The way I would frame it, John, is we need to meet people at their point of living, if you will. So probably not anyone's favorite topic is colorectal cancer screening. But I think with all of the public education, public awareness campaigns that have been launched recently, it is a conversation that people, patients, family members are willing to have. And that's potentially life-saving.

Colorectal cancer has been called one of the most preventable yet least prevented cancers. And it's because people either aren't aware that screening is available and effective or they just don't want to talk or think about it. Part of the goal that we're working on to try to change the current status quo and get more people screened is to raise the awareness around the number of effective options that are available even during current times where access to on-site screenings or willingness to go and see a doctor for a screening visit may be lower than prior to the COVID pandemic.

So the at-home test options are clearly part of the conversation. I think that the message that I would deliver to patients and providers is colorectal cancer screening doesn't have to stop and shouldn't stop. Because if we lose our focus, we will also create a situation where we've got delayed or new diagnosis of colorectal cancer that occur, which could have been avoided or caught earlier if people had taken part in one of the home-based screening or other strategies.

JOHN WHYTE: Now there's been new guidelines by the US Preventive Services Task Force in terms of what age should we start screening for people at average risk, but I want to step back for a moment because that can be confusing to patients. What does that mean average risk? Can we start off there in describing who's not at average risk?

PAUL LIMBURG: In general, colorectal cancer risk factors would include age, some personal medical conditions, things like inflammatory bowel disease. And family history is also important. So for average risk, it's generally patients who are otherwise healthy who don't have a personal history of a high risk condition and don't have close family members with colorectal or some other types of cancers.

JOHN WHYTE: But there's also some genetic variants as well that they could have inherited that would put them at greater risk. So the new screening guidelines start at-- let's review that in terms of what age should it start at.

PAUL LIMBURG: So the American Cancer Society came out in May of 2018 with a recommendation that screening should start at a younger age. Previously, most guideline groups had recommended for the general population begin at age 50. The American Cancer Society said based on emerging data, about 10% of colorectal cancer cases are now thought to occur in individuals younger than age 50.

So the American Cancer Society guidelines now state, begin at age 45. There are some draft recommendations from a very influential group called the United States Preventive Services Task Force. And in those draft guidance documents, the recommendation is now to start at age 45 as well.

JOHN WHYTE: And those are currently in guidance where the public can comment on. Let's talk about what are those different strategies that people can utilize for screening. It'd be nice to review for the audience what are the options.

PAUL LIMBURG: So there's really a couple of different categories. One is an endoscopic test. So colonoscopy is one of the most well known.

For that test, there is a bowel preparation procedure. There are some medication restrictions that are typically applied. Patients generally are sedated for that exam. And in many instances, it would take a day off of work to complete the colonoscopy.

There's a shorter endoscopy test called flexible sigmoidoscopy, which really only looks at about the last half of the colon and rectum. That one's not used as widely as it used to be because of advances with other technologies. There are radiologic tests, an older test called a barium enema, again not used as often as previously.

But CT colonography, in essence a CT scan, that can look inside the colon and identify structural abnormalities like polyps or cancers. That also requires a bowel prep prior to the X-ray, but no sedation typically. And then there are stool tests, and the stool tests either look for occult blood only, something called a fit test or sometimes a fecal occult blood test. And then there's the multitarget stool DNA test, which in addition to looking for occult blood, looks for 10 molecular markers.

JOHN WHYTE: And the timeframe of when one has to undergo repeat screening is different. Paul, I want to talk about the issue of disparity and how, particularly, people of color can be at disadvantage for getting colon cancer, not undergoing screening, and then having poorer outcomes when they do develop it. So how do we address that issue of disparity?

PAUL LIMBURG: Thanks, John. That is a real public health concern. We don't fully understand why different racial ethnic groups may experience higher colorectal cancer incident and mortality rates.

There may be contributions from biology, from accuracy of different tests and treatments or quality of treatments. There may be access-related issues with respect to screening, for example. I think the COVID pandemic, as in many ways, emphasized and probably made some of those disparities and challenges with access even harder for different populations subgroups.

So what we need to do is remember that colorectal cancer is a heterogeneous disease. One size doesn't fit all with respect to screening strategies, with respect to messaging, with respect to treatment or other parts of the conversation. So treating patients as individuals, coming up with molecular tools, coming up with targeted messaging strategies-- I think all of those are activities that can help us reduce what we know to be some substantial disparities in colorectal cancer outcomes.

JOHN WHYTE: Where do you think we're going to be in five years from now in terms of colorectal cancer incidence? Will we see a surge in the next few years because people haven't undergone screening because of the COVID pandemic? Will we see a decrease based on these advances that we've been talking about in terms of screening, in terms of looking at the molecular biology, being able to do test at home making it more convenient? What's your prediction?

PAUL LIMBURG: It really is a changing landscape. So with the COVID pandemic and with the delays in screening, there are estimates that maybe 19,000 new cancers will have resulted from the lower number of screening visits that happened early on in the pandemic. Maybe just under 5,000 otherwise avoidable colorectal cancer deaths over the next decade.

We need to change those numbers. Even prior to COVID, about a third of the screen-eligible population was not up to date with any of the recommended strategies. We need to all work together to make sure that people who should get screened, do get screened, and that they have access to and knowledge about whichever of those screening options works best for them.

JOHN WHYTE: And then finally, taking out the issue of genetic variants for some cancers. What can people do to prevent risk? Is it diet? Is it exercise? Is it stress? What's the latest that we know on prevention of colorectal cancer.

PAUL LIMBURG: From my perspective, John, the single most important thing that we could do is have everybody get screened and stay up to date with screening. In terms of behavior modification, you hit on some of the key factors. What I tell my patients is what's good for your general health is probably good for your colon health.

So eat a healthy diet that's rich in fiber and natural food products. Maintain a body weight that is as close to the normal range as you can get. Be active. Physical activity even beyond weight management probably has some health benefits associated with a more active lifestyle as well.

And there is even a link between tobacco use and colorectal carcinogenesis. So avoid smoking. Quit smoking if you can.

JOHN WHYTE: But Dr. Paul Limburg, I want to thank you for taking the time today to share your insights about some of the advances that we're making in terms of screening for colon cancer. And the importance, and I hope that everyone is hearing this, the importance to get screened and also based on those findings when you need to be rescreened. Thank you for the time.

PAUL LIMBURG: Appreciate it. Thanks, John.

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