An Alarming Increase in Early Onset Colorectal Cancers

Presentation by Dr Sunnie Kim, University of Colorado Comprehensive Cancer Center

At the 2023 Total Health Spring Oncology Review and Renew Conference, Dr Sunnie Kim from University of Colorado Comprehensive Cancer Center highlighted the current increases in colorectal cancer (CRC) cases occurring in younger individuals.

Epidemiologic Data

Dr Kim noted that, although the overall incidence of CRC has been steadily decreasing over the past 3 decades, largely due to increased awareness and screening, there has been, at the same time, an increase in the number of CRC cases being diagnosed in younger patients, under 50 years of age. The CRC incidence rate, for example, has increased dramatically when comparing patients born in 1960 as compared with those born in 1990. In addition, the incidence rate for both colon cancer and rectal cancer is predicted to increase by 90.0% and 124.2%, respectively, in the 20-34 age group and by 27.7% and 46.0%, respectively, in the 35-49 age group. The specific increase in younger CRC, Dr Kim noted, appears to be most prevalent across the developed countries of the world, including North America, Europe, and Australia. Dr Kim noted some key take home points on early onset CRC epidemiology, which are summarized in Box 1.


BOX 1. Younger Onset CRC: Some Key Take Home Points

  • Prevalence of younger onset CRC is increasing across developed countries, particularly in the non-Hispanic White population.

  • Early onset CRC accounts for approximately 10% of all new diagnoses.

  • The mortality associated with early onset CRC stands in marked contrast to the decline in incidence of later-onset CRC.

  • As a result of this epidemiologic trend in CRC, the median age of diagnosis has decreased from 72 years to 66 years.

  • It is expected that in the next 10 years, one quarter of all new rectal cancers and 10% of new colon cancers will be diagnosed in the under 50 age group.


Risk Factors

Some of the risk factors for early onset CRC which Dr Kim noted were hereditary factors. In particular, about 30% of those with early onset CRC have a first degree relative with CRC. The most common hereditary condition leading to early onset CRC is Lynch Syndrome, a condition which can be readily identified through genetic testing. Overall, about one quarter of patients with early onset CRC have a hereditary CRC syndrome. As such, major guidelines recommend genetic risk counseling and evaluation for all persons presenting with early-onset CRC.

The major constituent of early onset CRC continues to be sporadic (non-hereditary) cases, with, as noted above, an increased incidence in the developed countries of the world. Some of the possible contributing factors in this regard, Dr Kim noted, are believed to occur early in life and include diet, the normal bacterial colonization of the gut, antibiotic use, lack of exercise, exposures during pregnancy, smoking and obesity. Some of the possible dietary changes, believed to have occurred about 50 years ago include increased consumption of red meat and processed meats, and processed sugars, all of which are believed to increase CRC risk. Results from the Nurses’ Health Study II of over 85,000 women also demonstrate a nearly two-fold increased risk of CRC for patients who are obese. By comparison, a decreased CRC risk has been associated with consumption of whole grains, fish, and dairy in some studies.

Dr Kim also noted a matched case-control study conducted in the United Kingdom, comparing 29,000 CRC cases and 137,000 control patients which showed a dose-dependent increase in CRC with antibiotic use, although prolonged use of some types of antibiotics, such as tetracyclines, were protective for CRC, particularly for rectal cancers. These antibiotic exposures occurred more than 10 years prior to the CRC diagnosis, and suggest that CRC risk can be impacted by alteration in what is known as the gut “microbiome”, or the normal bacterial colonization of the GI tract. Overall, although research on this topic will continue, Dr Kim noted that as yet, there was no single discernable cause of early onset CRC that has been identified, and the risk is likely related to a combination of multiple factors.

Screening

At present, Dr Kim noted that only about 68% of those individuals who are eligible undergo CRC screening (typically with colonoscopy, which is considered the gold standard for screening). This could relate in part to a lack of understanding of CRC screening benefit, a lack of healthcare access, and/or a reluctance on the part of the patient to undergo colonoscopy. Dr Kim noted that even lower CRC screening rates are evident among the uninsured, among low-income individuals, and across racial/ethnic minority populations. In general, Dr Kim noted that people at average risk of colorectal cancer should start regular CRC screening at age 45, according to the American Cancer Society. For those individuals in the 76 through 85 age range, the decision to be screened for CRC should be based on a person’s preferences, their life expectancy, their overall health, and prior screening history. For those over age 85, CRC screening is not recommended. There are a number of available tests for CRC screening, including stool-based tests such as the fecal immunohistochemical test (FIT), recommended yearly, the guaiac-based fecal occult blood test (gFOBT), recommended yearly, and the multi-targeted stool DNA test (mt-sDNA), recommended every 3 years. The more visually oriented or structural examinations of the colon include colonoscopy, indicated every 10 years, CT colonography (virtual colonoscopy), recommended every 5 years, and flexible sigmoidoscopy, recommended every 5 years. Some general take home points regarding CRC screening are summarized in Box 2.


BOX 2. CRC Screening: Take-Home Points

  • CRC screening should begin at age 45, or 10 years before the youngest case occurring in the immediate family.

  • For older patients, i.e., age 76 through 85 years, the patient’s overall health should be considered.

  • Colonoscopy remains the gold standard for CRC screening.


Outcomes and Special Considerations

In terms of overall outcomes for patients presenting with early onset CRC, Dr Kim suggested that the data remain unclear at present. While some data suggest that younger patients fare better in their CRC course, for patients presenting with later stage of disease, outcomes are largely similar or even worse as compared to their older CRC counterparts. Some younger patients may also present with more advanced disease as a result of a delayed diagnosis and more aggressive tumor features. Dr Kim also noted some genetic differences which have been observed, for example, differences in mutational status when comparing between early onset and late onset CRC.

Dr Kim emphasized some of the special considerations for patients presenting with early onset CRC and the need for a multidisciplinary team in management. For example, because younger patients may not often think of CRC as a potential cause of their GI symptoms, patients may put off further evaluation, which can result in significant delays in diagnosis. A number of social and economic issues also pertain to the younger patient with CRC; these include concern over financial issues (as often this is a peak period for career earning), and/or insurance coverage for cancer care over the long-term. Other concerns over physical limitations/disabilities and/or emotional and quality of life issues, such as the prospect of living with a colostomy, also necessitate connecting with other CRC patients in a similar age range for social support. Lastly, patients in this age range may want to have a family, and Dr Kim notes that referral for fertility counseling is also important.

Summary

Summarizing, Dr Kim noted that the overall incidence of early-onset colorectal cancer is rising in developed countries, and this has been largely driven by higher incidences of rectal cancer. While no one risk factor accounts for this trend, Dr Kim lists factors such as diet, alcohol use, obesity, and lack of exercise as some of the more notable predisposing factors. She emphasized that patients presenting with CRC under age 50 should also be referred for genetic counseling to assess any familial risk. In light of this alarming uptick in early onset CRC, Dr Kim suggests that adults 45 and over should consider screening, and even earlier screening can be considered if there is a family history for CRC. She emphasized that colonoscopy remains the gold standard for screening. The unique patient challenges associated with early onset CRC also require multidisciplinary team management to address the medical, social, and psychological aspects of their disease, and survivorship resources are especially important.

Disclosure Information: Dr Kim listed no disclosures for this presentation.

You can see Dr Kim’s full presentation from the 2023 Review and Renew Conference here:

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