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Melanie Cole (Host): Welcome to UF Health MedEd Cast with UF Health Shands Hospital. I'm Melanie Cole, and I invite you to join us as we discuss colorectal cancer awareness. Joining me is Dr. Jesus Fabregas. He's an Assistant Professor of Medicine in the Division of Hematology and Oncology at the University of Florida College of Medicine, and he practices at UF Health Shands Hospital.

Dr. Fabregas, thank you so much for being with us today. Can you just help us as we get into this topic to recognize colorectal cancer as a major cause of morbidity and mortality? Tell us the prevalence and what you've been seeing in the trends.

Dr Jesus Fabregas: Well, hello, Melanie. Thank you very much for having me As you said, I am a practicing oncologist here at UF Health Shands Hospital. And the problem is big. We know that colorectal cancer is the third leading cause of cancer death in both women and men with an estimated of 52,000 or more persons in the US predicted to die of colorectal cancer in 2022. We know that it's most frequently diagnosed among persons age 65 to 74. And there is a disturbing trend. We are seeing more and more cases of colon cancer being diagnosed in people younger than 50 years of age.

So two to three decades ago, 5% of the new colorectal cancer occurred in this population less than 50 years of age. But currently, we are seeing up to 11% of the new colon cancer cases affecting young people. We know that the incidence is increasing. For example, in adults ages 40 to 49 years old, the incidence has increased 15% from 2000 up to 2015 and only approximately 70 to 75% of people are compliant with the screening. So it's important to screen and to diagnose early the problem.

Melanie Cole (Host): So we're going to get into the screening, but Dr. Fabregas, do you have any thoughts about why you think it is starting -- I read that in the literature as well -- that it's starting to affect the younger population. Do you have any theories about that? And do you envision possible screening at younger and younger ages?

Dr Jesus Fabregas: Yes, Melanie. Excellent question. There are many possible culprits for this disturbing trend. For one, we have the diet, more specifically the Western diet, diets that are high in red meat, diets that are high in sugars, in processed foods. Also, obesity, excessive alcohol consumption, inactivity, sedentarism, all of those have been shown in observational studies to be linked with early incidence of colon cancer. However, we do not have a definitive answer yet, so to speak. So the researchers continue to try and answer this question.

As far as the second part of the problem, if we should be screening patients younger, the answer is yes. Just last year, the United States Preventive Task Force changed its guidelines to start screening or at least to consider start screening patients at the age of 45, just because of these disturbing trends. Previously, it was 50 and above up to 74 and, in special cases, 84 years of age. But now, the guidelines say that starting at the age of 45 is very important for the average risk population.

Melanie Cole (Host): Well, then let's talk about the screening methods out there. As we know, the gold standard, the colonoscopy, one of the very few, not only screening, but preventive measures that we have for colon cancer, the guidelines that are set out by the US Preventive Services Task Force, as you said, have been changing. Is there any controversy on age? Tell us a little bit, whether it's 45 or 50, what are we looking at for colonoscopy now? What are the protocols?

Dr Jesus Fabregas: Adults aged 45 to 49 years of age, the USPSTF recommends screening for colorectal cancer. That is the new kid on the block, so to speak. Adults aged 50 to 75 years of age, there is a continuous recommendation to keep screening these patients with, like you said, colonoscopy. That's just one of the many options every ten years. And perhaps, there is a slight controversy in adults ages 76 to 85 years of age. And the answer is to personalize this screening, meaning that if it is a patient whose life expectancy might be limited due to severe or moderate comorbidities, then perhaps it doesn't make sense to do screening in this population. However, if it is a very healthy 76 to 85 years old person who has many years to live, then definitely those patients will require screening. At the end of the day, in these population subset, it's a decision made after a discussion between the provider and the patient.

Melanie Cole (Host): Well, it certainly is. So now, let's talk about colon cancer itself. Colonoscopy, not withstanding, if somebody is diagnosed, tell us a little bit about how it's staged and some of the symptoms at presentation.

Dr Jesus Fabregas: Thanks, Melanie, for the question. There are four stages, I, II, and III and IV. This is what I tell my patients, stage I is when the cancer is very small and it is limited exclusively to the colon. Stage IV on the other end of the spectrum is when the cancer has been widespread. It's when it's in the bones, liver, or when it's outside of the surgical field, when it is not curable for the most part, so to speak. Stage II is when the cancer is a little bit on the big side and it is starting to spread through the muscular layer of the colon. And a stage III is when the disease is local regional, when it is big and when there is heavy involvement of lymph nodes.

As far as the symptoms go, you have the typical symptoms of fatigue, weakness. These are nonspecific. However, some other symptoms such as blood in the stool, abdominal pain, weight loss, changes in bowel habits, rectal pain, or changes in the caliber of the tool are very important. I want to tell all the patients that it is important to seek medical attention with their primary care provider in case of any or a combination of these very telling symptoms. So awareness, early diagnosis are key.

Melanie Cole (Host): Certainly is. And now let's speak about some of the exciting advances in treatments for colon cancer in your field. For other providers, Dr. Fabregas, tell us a little bit about what's going on that's exciting, whether it's radiation, targeted therapies, immunotherapies, surgical intervention. Tell us what's going on in the field.

Dr Jesus Fabregas: All of that, Melanie. There are many exciting changes. For example, pembrolizumab is a checkpoint inhibitor, a type of immunotherapy that trains the immune system to attack colon cancer cells. This is a very effective treatment option for patients with advanced colon cancer. It primarily works in patients who have microsatellite instability-high disease. This is a marker that we check in the colon cancer tumoral sample once it is diagnosed, once it is resected or biopsied. On the side of the targeted therapies, we have anti-BRAF medicines. BRAF 3600E is a common mutation in patients with colon cancer. We have now approvals for targeted therapy with encorafenib, binimetinib and cetuximab to treat these patients once they have progressed on standard chemotherapy. Between targeted therapy, immunotherapy and newer chemotherapy combinations, there is hope for patients with colon cancer.

Melanie Cole (Host): Doctor, for these patients, engaging multidisciplinary teams for better outcomes is such an important part of the approach. Tell us a little bit about your team and how you utilize that multidisciplinary approach.

Dr Jesus Fabregas: Melanie, anybody who has a diagnosis of colon cancer wants to have a world-class team of experts on their corner. Thankfully at UF Health Shands Hospital, we have a strong multidisciplinary team comprised of interventional radiologists, radiation oncologists, medical oncologists, surgeons, specializing in colorectal malignancies that treat these types of disease every single day. We, for example, meet every Thursday from 6:30 AM to 8:00 AM, and we go through every single case of rectal cancer or colon cancer that is diagnosed IN our institution. And we go through the different therapeutic options for the patients. The surgeons say something, the medical oncologists give their opinion. And then the radiation oncologists, pathologists, the rest of the team weigh in. At the end, we come up with the best treatment plan for the patient.

Melanie Cole (Host): Is there anything you'd like to share with other providers as far as research studies or things on the horizon? What do you see happening? What would you like to see happening?

Dr Jesus Fabregas: Melanie, the field is changing rapidly. I am very passionate about circulating tumor DNA. Previously in the old ages, after a patient had surgery for colon cancer, we used only clinical factors to determine whether a patient needed chemotherapy or not. We looked at the size of the tumor, the evidence of lymph node involvement or not, the evidence of lymphovascular invasion, perineural invasion, CEA levels. However, now there is a game changer on the field and that is circulating tumor DNA, CT DNA. This is a personalized test that we collect from each patient based on the DNA of the patient's specific tumor. And it is a way to detect minimal residual disease after surgery. We at the University of Florida Health Shands hospitals, we have clinical trials using CT DNA to determine whether a patient will need or will benefit from chemotherapy or not after having surgery. So we are not blindly giving chemotherapy anymore. We are making decisions based on the latest cutting-edge personalized biomarker technology. And this is going to be probably approved in the near term. And this is going to be a game changer. This is just going to expand through all of the guidelines nationwide.

Melanie Cole (Host): Well, it certainly will. What an exciting time to be in your field, Dr. Fabregas. Thank you so much for joining us today. To refer your patient or to listen to more podcasts from our experts, please visit ufhealth.org/medmatters. That concludes today's episode of UF Health MedEd Cast with UF Health Shands Hospital. For the latest on medical advancements, breakthroughs and research, please follow us on your social channels. I'm Melanie Cole.