Melanie Cole, MS (Host): Welcome to MD Cast by Tampa General Hospital, a go-to listening location for specialized physician-to-physician content and a valuable learning tool for world-class healthcare. I'm Melanie Cole. Joining me today to discuss colorectal cancer is Dr. Carolina Martinez. She's an Assistant Professor of Surgery at the University of South Florida College of Medicine in Colon and Rectal Surgery Division.

Dr. Martinez, it's a pleasure to have you with us today. Tell us a little bit about the incidence of colorectal cancer. What are you seeing in the trends?

Carolina Martinez, MD: So, colorectal cancer is actually the third most commonly diagnosed cancer in males, and the second most common cancer diagnosed in females. It's also the second most common cause of cancer death in the United States. We see approximately 153,000 new cases of colorectal cancer in the United States every year, and just over 52,000 people die of colorectal cancer, which is a pretty significant number.

And then if we look at the lifetime incidence of colorectal cancer for individuals who are at average risk, this is about 4%, and that incidence is about 33% higher in males than it is in females, and 20% higher in African Americans compared to white Americans.

When we actually take a look at the trends, we see some good news over the last few years and we've actually found that the trend in colorectal cancer has decreased. And we see that decrease has been about 46% when we look at the year 1985 when it was at its peak to about 2019. We see that it's been declining both in males and females. And we've been attributing this to a variety of factors, but what we think it's mainly changes in lifestyle, such as fewer individuals smoking over the last few years, increased use of NSAIDs, but also the higher number of patients who are over the age of 50 who have been undergoing screening colonoscopies.

We see this as especially true in the late 2000s after Medicare had expanded its coverage to all its beneficiaries. The use of colonoscopy screening essentially tripled from 20% in the year 2000 to about 61% in 2018 for individuals who are 50 years and older. But one trend that has actually been concerning for us over the last several years is the increased incidence of colorectal cancer in younger patients. So, we've seen that from about 2011 through 2019. The rate has increased by 1.9% per year in individuals who are younger than 50 years of age, and this is especially true for rectal cancer as opposed to colon cancer. And we're not exactly sure why this incidence has increased in the younger population, but we think it could be multifactorial. It may be related to environmental factors or a change and reduction in dietary quality.

Melanie Cole, MS: So interesting. And thank you for that, Dr. Martinez. And we'll get into colonoscopy and screening guidelines, especially for that younger population. But tell us some of the risk factors for development of colorectal cancer. And while you're doing that, please discuss the role of genetics and family history in this risk and how it impacts our screening recommendations.

Carolina Martinez, MD: Absolutely. There are several risk factors that have been linked to the development of colorectal cancer and we can kind of divide these risks into risks that modify screening recommendations and those that don't really alter those recommendations. For the risks that don't alter recommendations, these are things that haven't necessarily been proven to cause colorectal cancer, but we've seen an association. And those are things like obesity, especially obesity at a younger age, diabetes, as well as the consumption of red and processed meats, which actually in 2015, the World Health Organization had classified processed meats as carcinogenic. Similarly, smoking and alcohol use also been associated with the development of colon cancer.

When we take a look at risk factors that alter colonoscopy screening, those would be things like hereditary colon cancer syndrome, such as Lynch syndrome or familial adenomatous polyposis, as well as patients who have inflammatory bowel disease, like ulcerative colitis or Crohn's disease. These are patients who are at increased risk of developing colorectal cancer. Their screening actually begins at an earlier age, which we can talk about a little bit later when we get to screening. Also, there are some studies that suggest that patients who've received pelvic radiation, such as radiation for prostate cancer, may have an increased risk of rectal cancer, as well as patients who have a history of cystic fibrosis. These individuals may have a two to five-fold increased risk of colorectal cancer. What we can see is that there are many risk factors for the development of colorectal cancer, Some of which can be modified, but others which cannot be modified. And this is why we have a lot of the screening regulations in place.

And then, when we're taking a look at the role of genetics and family history in colon cancer, we do see that it certainly does impact screening recommendations. Most colorectal cancers are actually sporadic in nature and not necessarily hereditary, but hereditary cancer syndromes do account for about 5% of colorectal cancers. As mentioned, Lynch syndrome and FAP, which is a familial adenomatous polyposis syndrome, these are the two most common hereditary cancers. Lynch syndrome, this is caused by a defect in one of the DNA mismatch repair genes. And it's characterized by an early onset of colorectal cancer with that median age being around 48 years of age. So, it's really important to know family history to determine if testing for Lynch is indicated.

And when we think about obtaining a family history, we divide it into the 3-2-1 rule, which is also known as the Amsterdam criteria. So, we look at individuals, if they've had three family members with any Lynch-associated cancers, that would be colorectal cancer, endometrial cancer, or renal pelvis cancer, just to name a few. And we also ask if there are two successive generations that have been involved with cancer, and at least one who was diagnosed before the age of 50. So, anyone who meets this criteria should be referred for genetics testing and also undergo early screening colonoscopy. And the guidelines are recommending colonoscopy screening to start around the age of 20 to 25 for these individuals and it's done about every one to two years.

For FAP, which is the second most common hereditary syndrome, this is characterized by the development of hundreds to thousands of adenomatous polyps. And patients are typically symptomatic at a very early age, around the age of 16, and it's almost a 90% chance of developing cancer by the age of 45. So, this changes the screening colonoscopy guidelines for those patients to start around the age of 13, and this is done every one to two years. So, we can see that genetics and family history certainly do play a huge role in screening recommendations.

Melanie Cole, MS: Well, they certainly do. And I'd like you to speak and expand on colonoscopy screening guidelines and how they've changed in recent years. So, you spoke about the indications for earlier screening colonoscopy, but what about for the average person? And what are we looking at now and how often based on obviously the results?

Carolina Martinez, MD: Current guidelines recommend screening all individuals at the age of 45. In 2021, the U.S. Preventative Services Task Force changed the screening age from 50 to 45 in average risk individuals. And they made this change because of the increased incidence of colorectal cancer in the younger populations. And this recommendation essentially starts again at the age of 45 and goes until the age of 75 if a colonoscopy is deemed to be normal. And this is typically repeated at about a 10-year interval. For patients between the ages of 76 to 85, the decision to continue screening colonoscopies has to be individualized and selective. And it should really take into account the patient's overall health and their personal risk for the development of colorectal cancer. And then, screening colonoscopies typically are not advised for individuals over the age of 85, but again this is a conversation that should be had between the patient and the primary care provider or their gastroenterologist.

Melanie Cole, MS: Dr. Martinez, as adherence to colonoscopy, despite its effectiveness, may be limited, do you feel that offering non invasive tests as a screening option may effectively improve adherence to screening? I'd like you to speak about some of the other options, because there are more and more in the toolbox now. Stool test, imaging test, there are all these different ones. Speak a little bit about those, the advantages and disadvantages.

Carolina Martinez, MD: Yep. So, I will start off by saying that the gold standard for screening for colorectal cancer is still through colonoscopy. It's still the most accurate for localizing and biopsying colorectal lesions. But that being said, we also know that only about 50% of individuals in their early 50s actually complete a colonoscopy. So, compliance and adherence is certainly a barrier, which is why I also do advocate for non-invasive tests, which also are a great option for those who do not want to undergo a colonoscopy.

There are several stool-based studies that have been shown to have an increased compliance and are also very effective. One of these is the FIT DNA test, which is also known as the Cologuard test, which is my personal favorite in the category of stool-based studies. This test uses molecular assays to look for KRS mutations to test for methylation biomarkers associated with colorectal cancer, and then it combines it with an immunochemical assay, which is a FIT test, to look for hemoglobin in the blood. This one's done every three years. And the advantage is that it does not require a bowel prep, does not require sedation, and also compliance and tolerance may be better than a colonoscopy. The disadvantage of this is that it may have a lower sensitivity to detect adenomas and cancers when compared to the colonoscopy. For example, the sensitivity for a FIT DNA test to detect a less than one centimeter adenoma is about 43%, but its sensitivity to detect colon cancer is 92%, which is still really good.

The FIT test, which is the fecal immunochemical test, which directly measures hemoglobin in the stool. This one's done annually, and it also does not require a bowel prep or sedation. But similar to the FIT DNA test, we can see that the sensitivity may be lower for detecting adenomas, but it's still pretty good in detecting colon cancer.

Another option for colon cancer screening that doesn't involve a colonoscopy or a stool-based study is a CT colonography. So with this test, it uses thin-sliced CT images that then does a 3D and 2D reconstruction to look for adenomas or masses. It does not require sedation. But the disadvantage is that it still does require a bowel prep, and it is mildly invasive, not quite to the point of a colonoscopy, but they do have to insert a catheter through the rectum to insert air or CO2 to be able to distend the colon for the test. And it also exposes the patient to radiation, which some patients may not agree to. But this one is done every five years and it also has a really good sensitivity to detect cancer and adenomas that are especially greater than one centimeter in size.

But all this is to say that each test has its own advantages and disadvantages. But at the end of the day, the most important thing is to be able to screen patients for colorectal cancer in any way that's possible so that we can continue to reduce that trend in colon cancer.

Melanie Cole, MS: Completely agree with that. And Dr. Martinez, if a patient is diagnosed with colon cancer, speak a little bit about some of the key considerations in determining the stage and extent of the disease. And while you're telling us that, give us a brief overview of the various treatment options for colon cancer, including surgery, chemo, radiation, because again, there are so many tools in the toolbox and this is really a more exciting time in colorectal cancer as they're coming up with so many new treatment modalities.

Carolina Martinez, MD: Once a patient is diagnosed with colorectal cancer, the next step is to do staging. So, we want to determine if this is localized disease, locally advanced, or metastatic because this is what will guide the management for this patient. Our staging is typically done with CT scans, CT of the chest, abdomen, and pelvis, typically with IV and oral contrast. But if a patient is diagnosed with rectal cancer, we then also include an MRI of the pelvis with a specific rectal cancer protocol that uses rectal contrast, or an endorectal ultrasound can also be utilized.

In addition to CT scans, we can also use an MRI of the liver. This can be helpful to characterize any liver lesions that appear suspicious on a CT scan but may not have a definitive appearance for metastases. So, an MRI can be helpful in being able to characterize these lesions better. There are also a series of laboratory tests that should be obtained. This would include things such as a CEA, which is our tumor marker, CBC, CMP and also circulating tumor DNA testing can also be obtained to follow these patients. We also recommend referral to medical oncology, colorectal surgery, and possibly radiation oncology if rectal cancer is the diagnosis.

And then, taking a look at some of the treatment options, so surgery obviously plays a pretty significant role in the treatment of colorectal cancer, because it can be curative, especially in those early stages. But we also need to understand that management of rectal cancer varies or differs from that of colon cancer.

Most patients who have colon cancer are usually managed with upfront surgery, but patients with rectal cancer will often require neoadjuvant therapy, and this involves chemoradiation and sometimes chemotherapy before surgery. We call this total neoadjuvant therapy. Neoadjuvant therapy for rectal cancer would be done for T3 or T4 tumors, those who have positive lymph nodes, or involvement of the mesoerectal fascia. This is considered locally advanced disease. And these patients are treated with either long-course chemoradiation therapy combined with 5FU, this is the conventional radiotherapy, or they can be treated with short-course radiation therapy. And the decision on which course to take would be something that would be discussed with the surgeon and the radiation oncologist. And for patients getting total new adjuvant after they've received chemoradiation, this is then typically followed by six cycles of chemotherapy, most often with FOLFOX or CAPOX. But this again would be a discussion between the surgeon and the medical oncologist as well to determine which regimen is best for the patient.

Once this is completed, patients are then restaged. And then, we talk about which surgical options are available. In 2020, the NCCN guidelines stated that patients who had achieved a complete clinical response to rectal cancer treatment, meaning that they did not have any evidence of residual tumor on digital rectal exam or MRI or sigmoidoscopy, these patients may be candidates for a non-operative approach with intense surveillance which is new for the last few years. But this is only recommended at institutions who have an experienced multidisciplinary team. And this is another reason why total new adjuvant therapy has served as a recommendation for patients who have locally advanced rectal cancer.

And then, switching gears and kind of looking at colon cancer, non-metastatic colon cancer. As I mentioned, curative intent colectomy should be considered upfront. Neoadjuvant treatment does not always play a role in colon cancer. But sometimes radiation therapy can be considered in very select cases who have T4 disease, meaning it's involving adjacent organs or it's locally advanced. But most patients end up going to surgery directly.

Melanie Cole, MS: Dr. Martinez, this is so interesting and you're giving us such comprehensive information. As we wrap up, tell us a little bit about your tumor board and how it's helpful for this cancer and why you've mentioned the multidisciplinary team a few times briefly. Please tell us why that's so important for these patients.

Carolina Martinez, MD: Yes colorectal cancer care really does require a multidisciplinary approach. We work very closely with various specialties. This includes, you know, our wonderful medical oncologist, our radiation oncologist, as well as our gastroenterologist and pathologist and other surgeons who are also part of our meetings. And I do believe that these meetings help us facilitate patient care in a more expedited fashion. It also helps us to coordinate care and be able to come up with treatment plans for patients, especially those who are very complicated patients. And it helps us discuss research options and trials that are available as well as alternative treatment options for patients who have advanced disease and who may not be candidates for surgery at the time, but the goal is to get them to that point.

And there are actually several studies that look at the positive effects of a multidisciplinary tumor board conference. And they show that patients who are discussed in tumor boards have improved survival compared to those who are not. And that these patients who are discussed also have a more accurate diagnosis and a more complete preoperative staging.

I do think that in order to be able to make progress towards continuing to fight against colorectal cancer, it has to be a team effort. And there is tremendous value in being able to incorporate our tumor boards in the care of these patients.

Melanie Cole, MS: Thank you so much, Dr. Martinez. What an informative episode this was. Thank you again for joining us and sharing your incredible expertise. And thank you for listening to MD Cast by Tampa General Hospital, which is available on all major streaming services for free.

To collect your CME, please click on the link in the description. For other CME opportunities, including live webinars, on-demand videos, and local events offered to you by Tampa General Hospital, please visit cme.tgh.org. I'm Melanie Cole. Thank you so much for joining us today.