Colorectal cancer in adults younger than 50 years old

The updated guidelines for colorectal cancer screening released by the American Cancer Society May 30 recommend that average-risk adults in the U.S. should start screening at 45 years of age.¹ Although this is a qualified recommendation, it is a clear indicator of the increasing concern regarding the rising incidence of colon and rectal cancer among younger adults. Data from both the Surveillance, Epidemiology, and End Results (SEER) registry and the National Cancer Database (NCDB) have consistently demonstrated the striking increase in the rates of colon and rectal cancer among adults ages 18–50.^2-4 For example, adults born in the 1990s are two times more likely to develop colon cancer and four times more likely to develop rectal cancer than someone born in the 1950s (see Figure 1). The exact cause of this dramatic rise in colorectal cancer among younger adults is unclear. Racial and ethnic disparities have been observed in epidemiology studies but offer an incomplete picture. Numerous other factors have been suggested, including sedentary behavior, obesity, diabetes, and the modern high-fat and low-fiber Western diet, although a definitive cause has yet to emerge.

The disease burden of colorectal cancer is substantial. In the U.S., it is now the third most common cancer, the leading cause of cancer-related deaths in nonsmokers, and the second most lethal cancer. Changes in screening recommendations will likely increase the use of health care services among younger patients but hopefully will decrease the incidence of advanced cancer diagnoses frequently seen in younger adults.

Figure 1. Trends in colorectal cancer incidence rates by age and year of birth, and by age and year of diagnosis, U.S., 1975 to 2014

Source: Wolf AMD, Fontham ETH, Church TR, et al. Colorectal screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA Cancer J Clin. 2018;68(4):250-281.

Colorectal screening options

Colorectal screening is categorized as either stool-based or visual-based screening tests. Stool-based testing—such as guaiac-based fecal occult blood test and multi-targeted stool deoxyribonucleic acid (DNA) testing (such as Cologuard)—may be easier to perform with minimal burden to the patient, but they require follow-up colonoscopy for a positive test. Unfortunately, long-term data on DNA stool testing is lacking.

Visual-based tests evaluate and can intervene upon structural changes in the colon and rectal mucosa. Although visual-based tests, such as colonoscopy and computed tomographic colonography, are more sensitive and have demonstrated decreased mortality, they are more expensive, require bowel cleansing, and have procedure-associated risks.

Biology of colorectal cancer in younger adults

Younger colorectal cancer patients present with more aggressive and advanced disease. Young-onset colon cancer presents as stage III/IV disease in 63.4 percent versus 49.0 percent (p < 0.01) of older-onset disease cases.3 Younger patients also are more likely to present with higher-grade tumors, unfavorable tumor morphology (mucinous and signet ring features), increased metastases, and greater lymph node involvement. Hereditary syndromes, such as Lynch syndrome and familial polyposis syndrome, may account for a subgroup of colorectal cancer in younger adults; however, most cases are not hereditary. The typical younger colorectal cancer patient is microsatellite stable and has a lower frequency of aneuploidy and BRAF sequence variation, a lower frequency of the CpG island methylator phenotype, and a greater frequency of hypomethylation of LINE-1 (long interspersed nucleotide element-1).⁵

Clinical trials

Younger patients with colorectal cancer are typically eager to learn about new treatments and to participate in clinical trials. They often have locally advanced and/or metastatic disease at presentation but typically harbor few medical comorbidities, making them excellent candidates for clinical trials. Enrollment of these patients in ongoing trials in colorectal cancer is the optimal approach to gain knowledge regarding their tumor biology, quality of life, and survivorship issues.

References

1. Wolf AMD, Fontham ETH, Church TR, et al. Colorectal screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA Cancer J Clin. 2018;68(4):250-281. Available at: https://onlinelibrary.wiley.com/doi/full/10.3322/caac.21457. Accessed August 21, 2018.
2. Siegel RL, Fedewa, Anderson WF, et al. Colorectal cancer incidence patterns in the United States, 1974−2013. J Natl Cancer Inst. 2017;109(8):27-32.
3. Bailey CE, Hu CY, You YN, et al. Increasing disparities in the age-related incidences of colon and rectal cancer in the United States, 1975−2010. JAMA Surg. 2015;150(1):17-22.
4. You YN, Xing Y, Feig BW, Chang GJ, Cormier JN. Young-onset colorectal cancer: Is it time to pay attention? Arch Intern Med. 2012;172(3):287-289.
5. Ahnen DJ, Wade SW, Jones WF, et al. The increasing incidence of young-onset colorectal cancer: A call to action. Mayo Clin Proc. 2014;89(2):216-224.