Are You At Risk? Cleveland Clinic Tool Predicts Early Onset Colorectal Cancer

Podcast Transcript

Dr. Scott Steele: Butts and Guts, a Cleveland Clinic podcast exploring your digestive and surgical health from end to end.

Hi again, everyone, and welcome to another episode of Butts and Guts. I'm your host, Scott Steele, the president of main campus and colorectal surgeon here at the Cleveland Clinic in beautiful Cleveland, Ohio. And today we're going to be talking about early onset colorectal cancer and specifically about some of the risks that may be able to predict this. And I'm very pleased to welcome our expert, Dr. Carole Macaron, who is an assistant professor of medicine and gastroenterologist here at the Cleveland Clinic. Carole, welcome to Butts and Guts.

Dr. Carole Macaron: Thank you. Thank you. It's a pleasure to join you today.

Dr. Scott Steele: So give us a little bit about your background for our listeners. Where are you from? Where'd you train? And how did it come to the point that you're here at the Cleveland Clinic?

Dr. Carole Macaron: I'm originally from Beirut. I completed my medical school at St. Joseph University in Beirut. And then I joined the Cleveland Clinic Interim Medicine Residency Program, subsequently, the Gastroenterology Fellowship program, and I've been in beautiful Cleveland ever since. I've been a practicing gastroenterologist with over 10 years of a clinical experience, focusing mainly on colon cancer prevention and more recently with a specific interest in younger adults.

Dr. Scott Steele: So we've talked a little bit in the past on other podcasts about colorectal cancer. So can you start by explaining what is Cleveland Clinic's early onset colorectal cancer risk predictor and how did your team become motivated to develop this specific tool?

Dr. Carole Macaron: Yes. I like to call it the Cleveland Clinic early onset colorectal neoplasia risk predictor because neoplasia is more of a broader term. The risk score predicts not only colorectal cancer, but also advanced pre-cancerous polyps. And it's targeting patients, individuals who are under the age of 45. The reason we created this tool is because colorectal cancer in young people has been rising rapidly. It is now the leading cause of cancer-related death in young adults. And the majority of cases are found at a late stage. Add to that, half of early onset colorectal cancer is happening in individual under the age of 45 who are not routinely screened. So all these facts push us to find a better way in identifying high-risk young adults, ideally early, using tools that could be widely available in all communities. So our short-term goal was to create that simple score that helps estimate someone's risk. In the long run, we would hope to develop a personalized screening program for adults under the age of 45 who are at risk. One that is easy to use, that is accessible, even in low resource settings.

Dr. Scott Steele: So you mentioned that early onset colorectal cancer has been rising in recent years. You gave us some statistics. Are there any more current statistics on this trend? And do we know why is this happening in this younger patient population?

Dr. Carole Macaron: Yeah, it's absolutely an ongoing issue and a debate. And a lot of research is now looking at trying to identify some of these risk factors. We don't know why it's happening. We know it's a persistent rise at least over the past 20 years. And we can say that one in 10 colorectal cancer that is diagnosed now is diagnosed in someone younger than age 50, what we call as early onset colorectal cancer. What is even more concerning is that colorectal cancer is causing more death in younger adults than ever before. What we wanted to do is we know that we are in an area at risk. We know that the Great Lakes region or Northeast Ohio is a hotspot for death related to early onset colorectal cancer. We thought, why don't we look at our records and see who are these patients who are developing early onset colorectal neoplasia? And can we identify some risk factors? And can we use these risk factors in estimating someone's risk and perhaps offering screening early? So this is all what prompted the Cleveland Clinic risk prediction score.

Dr. Scott Steele: Okay. Now it's time to walk us through that risk predictor. How does it actually work? What specific factors or variables does it take into consideration when you calculate someone's risk?

Dr. Carole Macaron: Sure. It's actually pretty simple. There are four pieces of information that you need to calculate someone's risk or your own risk. The four risk factors are sex, body mass index, which is calculated from weight and height, tobacco use and family history of colorectal cancer. Now, developing it wasn't that simple. We had to analyze a large database of over 13,000 patients under the age of 45 who had colonoscopies at the clinic over the past 10 years. We collected a variety of factors known to be linked to colorectal cancer and polyps. And by comparing patients who had cancer or advanced pre-cancerous polyps to those who had a normal colonoscopy, we identified those four risk factors that I just mentioned. And then using a fancy statistical method, we were able to combine these factors into a simple risk score.

So each factor is assigned a number of points. For example, someone who currently smokes or has smoked in the past receives three points, while someone who has never smoked gets zero points. The other factors are scored in a similar way. The points at the end are added up to give a total score, which ranges from one to 12. Adults with a score of nine or higher have more than 14% risk of early onset colorectal neoplasia, similar to the risk seen in people age 45 and older who undergo standard colorectal cancer screening. In a previous interview, I think I compared it to a magazine questionnaire where you just answer the questions and then you calculate your points at the end. This is really as simple as it can get.

Dr. Scott Steele: Carole, so who's the target audience for this tool? Is it for people of a specific aimed range? Can anybody use it to assess their risk? Are you aiming this that patients or patient family members would be able to use this or is this for providers?

Dr. Carole Macaron: Honestly, anyone can use the risk score. Ideally, it should be used in the primary care setting where conversations about colorectal cancer screening typically take place. The tool was developed for adults age 18 to 44 who are not currently included in routine screening based on our national guidelines, but the tool is not available like an online website. The paper was published earlier in the year so they can see it, everyone can calculate their own score, but at this point it's not actionable. So even if you have, let's say you calculate your own score and the score is high, you still have to discuss it with your primary care physician in the office.

Dr. Scott Steele: So this is great research, and as you said, that it has been published earlier in the year. So what were the key findings from this research that led you to have this predictor development? And Carole, was there any surprising risk factors that emerged from your data? I mean, we speak about people are symptomatic, changes in their bowel movements or have blood stool. So walk us through that.

Dr. Carole Macaron: Yeah. So when we developed this risk tool, we did not want to include people with symptoms, because we knew that people who will come in with bleeding or symptoms, they should undergo a colonoscopy. They're not going to rely on this risk prediction tool. So we only included patients who had no symptoms, who just came in for either a regular checkup or they had a family history that prompted the colonoscopy. And to be honest, there was no surprising risk factors in our study. The four factors that we included in this score have all been known risk factors for colorectal cancer. What is new though is that this is the first time these simple factors have been combined to create an easy to use score, specifically for the very young adults. There are several other early onset colorectal cancer risk tools that already exist, but many rely on like genetic testing or large amounts of detailed information on environmental exposure and dietary information, which makes them harder to use in a primary care setting. And surprisingly, our simple score performed just as well as these more complex models.

Dr. Scott Steele: So how accurate is this risk predictor? How do you validate it? And is there something that we need to know in the devil's in the details about the difference between an increased risk and a definitive diagnosis?

Dr. Carole Macaron: Yes, yes, absolutely. Well, the score I would say has moderate accuracy and it was validated internally within our institution using a separate group of young adults. And it's important to note that when we say increased risk, it simply means that they have a higher probability of having one or more advanced pre-cancerous lesions or colorectal cancer. It does not mean they have cancer. The score is a statistical tool that helps identify people who may benefit from earlier screening. It's not a diagnosis.

Dr. Scott Steele: If someone uses the risk predictor and discovers that they have elevated risk, what do you suggest that they do? How do they follow up with their healthcare provider about this?

Dr. Carole Macaron: Well, at this point, as I said earlier, the risk prediction score is not yet actionable. It means it still needs more testing before it can be used to guide medical decisions. And our team is currently working on validating the score in other populations and testing it ideally in real time. We also hope to improve the score by adding perhaps additional informations that were not included in the original study. For now, I would say if someone receives an elevated risk score or calculate their own score and the score is high, then best next step is simply to discuss it with their healthcare provider. They can review their personal risk factors, symptoms, and family history, and decide whether any further evaluation or lifestyle changes are appropriate.

Dr. Scott Steele: So we talked a little bit about how you envision this tool kind of changing the conversation. So you are passionate about colorectal cancer screening. So can you talk about maybe the next evolution, if you will, of the utilization of this tool? Or what's on the horizon for this?

Dr. Carole Macaron: I think the next step would be to help implement or develop a personalized screening program that offers screening tests. It could be a colonoscopy or a tool-based test to people who we identify being at higher risk. The problem with universal screening is the uptake. People won't go and get the test. We know at least for patients age 45 to 49, screening uptake is about 20%. So lowering the age, starting screening early may not be alone the answer. Perhaps risk certification, having an estimate of someone's risk may push someone to undergo screening. And such a risk certification tool could be integrated into the electronic health records. So it can help primary care providers have informed discussions about colorectal cancer screening with their patients in the office.

Dr. Scott Steele: So are there any other upcoming things on the horizon in terms of your research as it pertains to either this risk prediction or early onset colorectal cancer in general that you're able to share with us?

Dr. Carole Macaron: I think what we're working on is securing funding for a large prospective study where we could test the score in real time and offer one of the screening methods and see how does it work, how effective is it in identifying our high-risk patients or patients that are at increased risk? And that might be an opportunity for patients who are interested in the future to actually participate in such a study. And that will help advance early detection efforts, for sure.

Dr. Scott Steele: I certainly see something that is needed out there. So now it's time for our quick hitters, a chance to get to know our guests a little bit better. So first of all, Carole, what was your first car?

Dr. Carole Macaron: It was an Opel. It's like I think a European manufacturer. I have never seen such a car here in the United States.

Dr. Scott Steele: And do you have a favorite movie?

Dr. Carole Macaron: I like The Pursuit of Happiness.

Dr. Scott Steele: Nice. And so is there a place that you would like to travel to that's still on your bucket list?

Dr. Carole Macaron: Still on my bucket list? I mean, we've been trying to visit Europe every time we go back home. So I think probably next step is going to be Italy.

Dr. Scott Steele: Beautiful. And finally, is there a, if you will, superhero power that if you got to choose just one and magically could have it, what would it be?

Dr. Carole Macaron: Control time. Be able to pause at any time, fast-forward, rewind, whatever.

Dr. Scott Steele: Fantastic. And so give us a final take-home message for our listeners regarding this early onset colorectal cancer.

Dr. Carole Macaron: I'll say colorectal cancer can be prevented and can be caught early. Please get screened. Whatever screening method you like, just get screened. There's more in the horizon. We should be able to improve our strategies, particularly when it comes to young adults. So while our risk score is not yet ready for clinical use and is not a diagnosis, we do hope to test it prospectively. And if we're successful, this is an opportunity for young adults to participate in such a study. So we'll definitely keep everybody updated.

Dr. Scott Steele: Fantastic. And so for more information on the Digestive Disease Institute, otherwise known as DDI here at the Cleveland Clinic, please call 216-444-7000. That's 216-444-7000. You can also visit clevelandclinic.org/digestive for more information. That's clevelandclinic.org/digestive. Dr. Macron, thanks so much for joining us on Butts and Guts.

Dr. Carole Macaron: Thank you so much for having me. This was a great conversation. Thank you.

Dr. Scott Steele: That wraps things up here at Cleveland Clinic. Until next time, thanks for listening to Butts and Guts.