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Dr. Buch:
For young adults who are diagnosed with colorectal cancer, a multidisciplinary approach is key.  Diagnostic and treatment considerations are specific to their age. 

Welcome to GI Insights on ReachMD.  I’m your host, Dr. Peter Buch, and joining me today to discuss this compelling topic is Dr. David Liska.  Dr. Liska is Section Chief of Oncology, Department of Colorectal Surgery, Director, Weiss Center for Hereditary Colorectal Neoplasia, Director, Center for Young-Onset Colorectal Cancer, and Associate Professor of Surgery all at the Cleveland Clinic.

Dr. Liska, welcome to the program.

Dr. Liska:
Thank you so much for having me.

Dr. Buch:
To start us off, Dr. Liska, can you talk about why we’re seeing a spike in young patients with colon cancer?  And can you share some key statistics?

Dr. Liska:
That’s an excellent question, and the short answer is that we don’t have a full answer of why this is happening; but in terms of the key statistics, it’s important to realize that since the 1990s, we’ve been seeing an over 50 percent increase in the colorectal cancer in young people, and what we mean by that is cancer in people under the age of 50.  That’s how it’s generally defined.  So that means that it’s about a one to two percent increase per year for young people.  And this is an even steeper increase in the very young, so people under the age of 40 or even under the age of 30.  And the rise is also higher in people with rectal cancer as opposed to colon cancer.  And currently, the incidence of colorectal cancer in people under the age of 50 is about 20,000 per year with close to 4,000 deaths each year.  By 2030, we expect that colorectal cancer will be the number one cause of cancer-related deaths in people under the age of 50.  So those are some very strong statistics.

Now the question that you asked about—why are we seeing this spike in young people?  We don’t really know, but one thing that has been seen is that we see this birth cohort effect, which means that there’s probably a shared environmental exposure that is leading to these increased risks in colorectal cancer because we see it not only here in North America; we see it globally in developed countries.  We’re seeing the same birth cohort effect where people born more recently are at higher risk for colorectal cancer, again indicating that there’s some sort of short shared environmental exposure or experience that is leading to this increase. 

Dr. Buch:
So can you just share with our primary care colleagues how alarm signs might be useful in making an early diagnosis?

Dr. Liska:
Yeah.  So the key thing to realize in young people with colorectal cancer, especially those that are under the age of 45 because just recently the screening age was changed from age 50 to age 45 because of the rise in young-onset colorectal cancer, but since most of these people are not yet at the age of screening, the way to diagnose that they have colorectal cancer is secondary to symptoms.  And one thing to keep in mind is that young people more likely when they have a colorectal cancer, it’s more likely to be on the left side of the colon, so rectal cancer, left-sided colon cancers are more common in young people than in older people.  And what that means is that symptoms are more likely related to having a left-sided colon cancer, and what that is a lot of them will present with bright red blood per rectum or blood on the toilet paper because left-sided tumors are more likely to present with red blood as opposed to right-sided colon cancer where you often don’t see the blood.   The more subtle sign is a change in bowel habits, which we know there’s many different reasons that can cause change in bowel habits, but if there’s a consistent change either from a person who was regular to then being constipated or then having diarrhea, both of these can be due to partially obstructing lesions in the colon, especially in the left colon, so that’s an alarm symptom that if it’s persistent and consistent, that should definitely warrant a workup.  Weight loss that’s otherwise unexplained, weakness or anemia that’s unexplained, is another sign to worry about.

Dr. Buch:
Thank you for that.  And how does a multidisciplinary approach help to provide the best personalized care plan for these patients?

Dr. Liska:
Another excellent question.  And so like I mentioned, young people are more likely to have rectal cancer.  Rectal cancer is often treated with chemoradiation, and then surgery, so that inherently requires a multidisciplinary approach.  All rectal cancer patients should be reviewed at a multidisciplinary tumor board so that they can get the best possible treatment and a high chance for cure with the optimal quality of life.  We know that it’s important for them to do genetic testing and counseling, so you need a genetic counselor to be involved with your team when taking care of young people.  There’s issues with fertility the treatment of colorectal cancer can affect, so you want to make sure you focus on that. 

A lot of young people are more likely to present with more advanced disease, with metastatic disease.  So whenever we have metastatic disease, especially in young people who can tolerate more aggressive treatments, meaning more aggressive chemotherapy, but also more aggressive surgical treatment—for example, when we have a young person with a colon cancer that has metastasized to the liver, we frequently will offer them surgery.  That will take care of both of the primary tumor and the metastatic lesions.  So again, that’s another reason that it’s important to have a multidisciplinary approach so you can address these concerns.

There are many psychosocial concerns that affect young people more than older people.  So in terms of the social support needed, financial support is a huge issue, so it’s important that people taking care of young-onset colorectal cancer that you have access to social workers who can help with these concerns as well.

Dr. Buch:
Thank you.  Now what’s the importance of microsatellite instability, immunochemistry, and something that you just mentioned, germline genetic testing for younger patients?

Dr. Liska:
All of these are important, and like I just mentioned, we’ll start with the germline testing first.  So germline testing, that’s usually a blood test or a saliva test, looking for any inherited colorectal cancer syndromes. 

And we looked at this recently here in our young patients, to see A, how many of our young patients have a pathogenic mutation that can increase their risk for other cancers or other colorectal cancers, and we found that it’s about 21 percent in our patients.  So it’s really important to have these patients be seen by a genetic counselor so they can get germline testing so that if you find the pathogenic mutation that means that they have hereditary cancer syndrome.  Number one, you might treat these patients themselves differently.  But number two, it can have implications for their remaining family and for the patient himself in terms of how aggressive you have to be about surveillance and screening for metachronous cancers.  So that’s importance for germline testing.

In terms of microsatellite instability or immunohistochemistry, about 15 percent of patients with colorectal cancer will have microsatellite instability, which is a genetic test on the tumor specimen or immunohistochemistry on the tumor specimen looking for mismatch repair deficiency.  And what that means is the mismatch report proteins that are responsible for fixing errors in DNA, and when you have that mismatch repair deficiency your tumor develops a lot of different mutations, it’s important for prognosis where we found that mismatch repair deficient.  Patients usually have better prognosis, and that can have implications in the type of treatment you are proposing, but more importantly, now we’ve also found that these patients are the ones that are very sensitive to immunotherapy, which can have huge implications, especially in the metastatic setting, but we’re also learning in the new adjuvant setting that in some patients immunotherapy can have huge implications on outcomes, so that’s why it’s important that any time you are diagnosed with a colorectal cancer that we check for mismatch repair deficiency or microsatellite instability, which get at the same thing.

Dr. Buch:
For those just tuning in, you’re listening to GI Insights on ReachMD.  I’m Dr. Peter Buch, and I’m speaking with Dr. David Liska about colorectal cancer in young adults.

So let’s turn to some treatment options, Dr. Liska.  Do more aggressive adjuvant therapies benefit these young patients?  And what should we know about immune checkpoint inhibitors?

Dr. Liska:
So in terms of the question if more aggressive adjuvant therapies benefit these young patients, so that’s somewhat controversial still, we know that young people can usually handle more aggressive treatments, be it adjuvant, neoadjuvant, or even surgeries.  So the thinking is that if we treat them with more aggressive treatments that they can handle without increasing their side effects then we should be able to achieve better outcomes.  The data isn’t really out yet to tell us if that’s true, and there’s some data that suggests that we’re actually overtreating young people.  Again, because of the shocking nature of seeing a young person with a colorectal cancer, especially when it’s metastatic, some people get treated maybe more aggressively than they need to without necessarily having any benefits from it.  So we have to be careful in not overtreating young people just because they’re young.  But that being said, if we think that more aggressive treatment will be beneficial—and like I said, for surgery, if we can really resect all visible disease—it has been shown that these patients do better in terms of long-term survival, and we do know that young people can handle more aggressive surgery.  So again, it has to be done judiciously, but in terms of immune checkpoint inhibitors, it’s been clearly shown now that immune checkpoint inhibitors are really a gamechanger in patients that have mismatch repair deficient colorectal cancer.  So what we have found is that when we treat those patients with immune checkpoint inhibitors, we unleash the patient’s innate immune system against the tumor, and that has been shown to have dramatic improvements in survival for metastatic patients.  But also in the neoadjuvant setting, we’ve seen incredible responses for these subset of patients that have mismatch repair deficient tumors where they really benefit from immune checkpoint inhibitors.

Dr. Buch:
Before we close, Dr. Liska, what resources are available for patients who are looking for accredited programs and quality care?

Dr. Liska:
In terms of rectal cancer in general, the Commission on Cancer has recently initiated the National Accreditation Program for Rectal Cancer, otherwise known as NAPRC, and there are multiple programs throughout the country that went through a very rigorous process of going through quality measures.  So people with rectal cancer should really look out for programs in their vicinity that are accredited by the National Accreditation Program for Rectal Cancer care. 

For young people with any colorectal cancer, I think it is important for them to make sure that they are being treated by a multidisciplinary team where the care is not fragmented.  When a young person is diagnosed with colorectal cancer, the amount of information that gets thrown at them in terms of different treatments, different possible side effects, is just a huge information overload, and it can be extremely overwhelming for patients.  They need a lot of understanding in terms of what’s going on and what they can expect, not only from the immediate treatment but also from survivorship and surveillance after that.  So if they have access to a center that’s dedicated to the care for young patients with colorectal cancer, that’s excellent; but even if there’s no such center in their area, making sure that they’re being treated by a multidisciplinary team that works in a coordinated fashion, that’s really critical and can make a huge difference.

Dr. Buch:
I want to thank my guest, Dr. David Liska, for educating us about the extremely important topic about how colorectal cancer is affecting young patients.

Dr. Liska, thanks so much for being here today.

Dr. Liska:
Thank you so much for having me.

Dr. Buch:
For ReachMD, I’m Dr. Peter Buch.  To access this and other episodes in this series, visit GI Insights on ReachMD.com where you can Be Part of the Knowledge.  Thanks for listening.