Treating Early Onset Colorectal Cancer in Young Adults

Early onset colorectal cancer (CRC) is a global phenomenon, in which young adults between the ages of 20 and 49 are being diagnosed with advanced stage disease. Trends in CRC show a decrease in the incidence overall, which is predominantly attributed to screening. In terms of CRC disease type, the SEER database rates show that colorectum and colon cancer have a 3% decline per year, and rectum cancer has a 2-year decline. Despite these trends, early-onset CRC in young adults between the ages of 20 and 49 has increased by 67%.

In a presentation at the 2020 School of Gastrointestinal Oncology (SOGO 2020), Andrea Cercek, MD, covered these trends and also looked towards the future of CRC in this younger population. It had been hypothesized that by 2030, the incidence of CRC in young adults will nearly double. In particular, 10.9% of colon cancers and 22.9% of rectal cancers will be seen in patients between 20 and 49 years old who do not currently fall into the screening guidelines.

As a strategy for preventing the doubling of CRC cases in young adults, experts are investigating the etiology of the rising incidence. This includes studying the lifestyles of these patients, how diet and body mass factor into their disease, how the microbiome may impact the incidence of CRC, and how early antibiotic exposure may come into play.

In an interview with Targeted Oncology following SOGO 2020, Cercek, medical oncologist, section head, Colorectal Section, co-director, Center for Young Onset Colorectal Cancer, Memorial Sloan Kettering Cancer Center, discussed the rising incidence of CRC in young adults in detail. She also advised community oncologists who encounter these patients in their clinics.

TARGETED ONCOLOGY: Statistics show that the rate of CRC is decreasing overall, but the incidence in young individuals is increasing. Can you discuss what factors are contributing to both of these trends?

Cercek: Since the mid-1990s, the incidence in young patients under the screening age or under the age of 50 has been rising steadily by 1 to 2% on. It's a global phenomenon, and we don't know what the factors are that are contributing to [these trends]. It must be some environmental influence. It is potentially behavioral or something that you're ingesting. This is something that's occurring not just within the United States but also worldwide.

TARGETED ONCOLOGY: At Memorial Sloan Kettering Cancer Center, what relevant characteristics have you seen in young patients with CRC?

Cercek: We see quite a few patients with the young-onset CRC because we're a large referral center. About one-fourth of our patients have been under the age of 50 and what we noticed several years ago was that the patients biologically behave similarly to patients over the age of 50, but they certainly have more needs surrounding their diagnosis, with their treatments, and into survivorship than patients who are at the average onset age in their late 60s or 70s. We really felt that establishing a good support network and a good referral basis for ancillary services, like sexual health, fertility, social work psychology, and psychiatry, was very important for these patients early on, which is why we opened a center dedicated to these patients. It is a virtual center that provides early intervention and early access to support services, as well as dedicated oncologic care from medical oncology to radiation oncology and surgery.

The second goal of our center was to try to dive into the ideology of this increase and study the disease biologically and molecularly. We study risk factors and the microbiome to see if perhaps there are some changes that are occurring in these patients that are leading to cancer at such a young age.

TARGETED ONCOLOGY: We know that the majority of these patients are diagnosed in the later stages. What challenges does later diagnosis cause?

Cercek: It’s difficult because exactly as you said, they're diagnosed in the later stages, and we're not entirely clear if that's due to the fact that they're young and perhaps dismissed their symptoms. Maybe it's a hemorrhoid rectal bleeding. That's 1 of the more common

presenting symptoms of these young patients because they do tend to have more left-sided and rectal tumors. Often, we see that their providers who are either internists, gastroenterologists also dismissed the symptoms. They don't think this could be CRC just because it's not typically for someone in this age group.

There was a nice survey done by the Colorectal Cancer Alliance, where they found that a large percentage of these patients actually presented to several health care providers before their diagnosis. This alludes to the fact that perhaps it is late diagnosis that is the problem and not necessarily very aggressive disease that is causing the patients to present with more advanced-stage disease.

TARGETED ONCOLOGY: What percentage of patients are over treated and what advice do you have for preventing this?

Cercek: I think that's a real challenge. As medical oncologists, surgeons, and radiation oncologists, when we meet a young patient and they're physically fit with no other medical comorbidities, we want to try our best to attack the cancer. Because their disease is believed to be more aggressive, some data have been published showing that young-onset patients tend to get more chemotherapy and more aggressive chemotherapy. Toxicities in young patients are not addressed as well as they are in patients of the average onset age, but I think that the key question here is whether the biology different. We need to know if it is necessary to give young patients such aggressive treatment or if we can treat them the same as any patient with CRC. I think more and more data are pointing to that end showing that perhaps it’s not the biology that's different, but it's our own reaction to treat them more aggressively. This is an important question to answer because many of these patients have long-term treatment. The average number of years now is between 2 to 3 years, even in the setting of metastatic disease. It's important to think about the toxicity that our treatment causes in the immediate time during therapy and also into survivorship.

TARGETED ONCOLOGY: What are some strategies for approaching treatment of these patients and possibly improving survival?

Cercek: The most important thing is taking a diverse look at the biology. Physicians should do the typical molecular testing that we do for all of our patients, which includes microsatellite instability (MSI) testing. A number of these patients have sporadic microsatellite stable tumors. They do not have MSI-high tumors, although a large proportion do have Lynch syndrome, which may be undiagnosed, and that's always critical to look at, as well as RAS and BRAF. There are a number of studies now evaluating BRAF mutations in the first-line setting, and that's important to keep in mind even in these patients that have more left-sided than right-sided tumors, which points to potentially less BRAF. It’s still important to look at that, as well as other markers like HER2 that could be used in further lines of therapy that are in development in clinical trials. That is critically important in young patients as well as all CRC patients that have stage VI disease on.

The other thing is that we have to look at the biology as you would with our standard lines of chemotherapy and always consider if there's any potential for any regional interventions that might prolong life or potentially offer time off of chemotherapy. I think that's the message for providing these patients with the support that they need early on.

One goal at our center is helping these patients through this point in their lives where there is a significant amount of financial toxicity. These patients may be just starting their careers or they’re the sole breadwinners for their family. Treatment affects all of that, and it is important to keep in mind when we're caring for the patient. Some of them don't have support services. Some of them are starting families, and there is a concern about fertility preservation. It's an important thing to bring up even if we believe that perhaps they won't be able to have children. People need varying degrees of support. I think a multidisciplinary approach is important, and my hope is that it helps them throughout treatment and then a swell for many into survivorship.

TARGETED ONCOLOGY: Is there any advice that you can give to community physicians who were treating these patients in their clinics?

Cercek: I think what is critically important will be all of our efforts, and this is, as I mentioned, a global effort to try to elucidate the underpinnings of this disease. Why is it happening early? Why has there been a persistent rise over the last 3 decades? What are these young patients exposed to? What are the risk factors?

We have to try to identify the population that's at risk to then offer them screening early on because, as we all know, CRC is actually preventable with the whole colonoscopy and polypectomy. This to be the case in our young patient as well.

_Reference

_{Cercek, A. Treatment of patients with Young Onset Colorectal Cancer. Presented at: 2020 School of Gastrointestinal Oncology; March 21, 2020.}