Colorectal cancer (CRC) is the second most common cause of cancer death in both men and women combined in the United States, as well as the third most common cancer diagnosis in both men and women.1 CRC poses a significant healthcare burden to patients, with recent data collected from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program and the Centers for Disease Control and Prevention National Program of Cancer Registries predicting that an estimated 147,950 people will be diagnosed with CRC, and approximately 53,200 will die from CRC in the United States in 2020.1

Patients younger than 50 years of age will represent 12% of these new cases and 7% of deaths due to CRC.1 This has led to an approximate 51% increase in CRC among patients younger than 50 years of age since 1994.2

Overall, there is a declining incidence of CRC in older age groups but an increasing incidence in younger patients. Data from 2012 to 2016 has shown incidence rates rising by 2.2% annually overall.1

Interestingly, this increase in incidence is also driven by more advanced cancers with both local and regional spread at time of diagnosis.1 For example, the average annual percent change in CRC incidence with regional spread increased from 2.7 between 2007 and 2016 to 4.3 between 2012 and 2016.1


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The average annual percent change in CRC incidence with distant spread was stable at 2.5 when compared during the same time frames. About 26% of CRCs are diagnosed with a distant stage in patients less than 50 years compared with 23% in patients between 50 and 64 years of age, and 19% in patients aged 65 years and older.1  

The median age of diagnosis has decreased from 72 years of age (2001-2002) to 66 years of age (2015-2016).1 Location of the tumor also varies based on age, with patients younger than 50 years most commonly presenting with rectal tumors (37%), followed by tumors in the distal colon (25%).1

CRC incidence rates now are similar in non-Hispanic Whites between 20 and 49 years of age (14.1 per 100,000) as those found in African American patients.1

This increased incidence of CRC in younger patients is not isolated to the United States. Similar increases in incidence findings have also been found in other countries, including the United Kingdom, Australia, Canada, and Germany.1 

CRC mortality can also vary by age. From 2008 to 2017, death rates decreased by 3% per year in patients 65 years and older, and by 0.6% per year in patients between 50 and 64 years.1 Conversely, death rates increased by 1.3% in patients younger than 50 years. This increase is most concerning in non-Hispanic Whites, among whom death rates increased at 2% per year, as was first noted in 2004.1  

As may be expected, patients with CRC who are younger than 50 years have higher 5-year relative survival rates compared with patients over 50 years at every stage of diagnosis. However, overall survival is similar between patients younger than 50 years (68%) and patients between 50 and 64 years (69%), based on younger patients receiving a diagnosis at increasingly later stages.1

Many of these findings prompted a change to the American Cancer Society CRC screening guidelines for average risk adults; as a result, an update was published in 2018.2 For this 2018 update, authors conducted a modeling analysis that led to a qualified recommendation for starting screening at age 45 years for all average risk patients. Screening can be conducted using colonoscopy, a high-sensitivity stool-based test (multitarget stool DNA test, fecal immunochemical test, guaiac-based fecal occult blood test) or a structural examination such as CT colonography or flexible sigmoidoscopy. This was a “qualified” recommendation — although there is evidence of a clear benefit, there is a lack of data with respect to patient preferences and values along with overall benefits and harms. 

Although the updated 2018 American Cancer Society guidelines are still relatively new and have not yet been incorporated into other societal recommendations, there is developing data on how these guidelines are being applied in the real world. Recently, a group of investigators led by Lynn F. Butterly, MD, of the Geisel School of Medicine at Dartmouth in Hanover, New Hampshire, evaluated colonoscopy outcomes in average-risk patients between 45 and 49 years of age who underwent colonoscopy; findings were published in the American Journal of Gastroenterology.3

Study authors utilized the New Hampshire Colonoscopy Registry to compare outcomes in average-risk patients both younger and older than 50 years of age. Prevalence and adjusted risks for advanced neoplasia (polyps >1 cm, villous, high grade dysplasia, and CRC) and clinically significant serrated polyps (>1 cm hyperplastic polyps, sessile serrated polyp, traditional serrated adenoma, and proximal hyperplastic polyp >5 mm) were calculated.

Over 40,000 patients were evaluated (n=40,812), with increasing prevalence of advanced neoplasia as age increased: In patients younger than 40 years, prevalence was 1.1%. This prevalence increased with age, to 3.7% in patients 45 to 49 years, 3.6% in patients 50 to 54, 5.1% in patients 55 to 59 years, and 6.7% in patients 60 years and older (P <.0001 between all groups). 

Similar findings were noted with clinically significant serrated polyps: Prevalence was 3% in patients 40 years of age or younger, 5.9% in patients 45 to 49 years, 6.1% in patients 50 to 54 years, 6.7% in patients 55 to 59 years, and 6% in patients 60 years and older. Study authors concluded that there was an increased risk of advanced neoplasia in patients 40 years or younger, with similar rates between 45 to 49 and 50 to 54 years. It is important to note that this study included only patients from New Hampshire; therefore it may not accurately depict patients across the United States.  

Despite clear evidence of increasing rates of CRC in younger patients, the exact pathophysiology underlying this trend is not completely understood. This increase may be multifactorial and is likely more complex than what are considered “traditional” risk factors such as smoking, obesity, diet, and family history.4,5 Additional explanations potentially include unrecognized hereditary syndromes and family history of CRC or advanced adenomas, “compounding” genetic defects that accumulate over time, environmental exposures, and alterations in the gut microbiome mediated by excess antibiotic use.4,5 Many patients will report a first-degree relative with a history of colon polyps, but details are often lacking — which makes determining accurate screening age challenging and may lead to a delay in diagnosis of advanced neoplasia.

As more data accumulates, it will be interesting to see if there is a continued trend toward screening younger patients and if insurance providers consistently cover these procedures. Determination and documentation of whether a colonoscopy is diagnostic, screening, or surveillance can have a significant impact on insurance coverage. This type of information is important to include when evaluating a patient for a colonoscopy, especially if they are younger than 50 years. 

While the pathophysiology behind CRC in younger patients continues to be researched, there should be a continued emphasis on changing modifiable risk factors that can contribute to at least half of all CRC cases: Risk factors include diet, obesity, lack of physical activity, and high alcohol consumption.1 These types of interventions should be applied as early as possible in adult patients, with hopes of altering the current rates of CRC in younger patients.    

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References

Siegel RL, Miller KD, Sauer AG, et al.  Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020;70(3):145-164. 

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

Butterly LF, Siegel RL, Fedewa S, Robinson CM, Jemal A, Anderson JC.  Colonoscopy outcomes in average-risk screening equivalent young adults: data from the New Hampshire colonoscopy registry. Published online August 21, 2020. Am J Gastroenterol. doi: 10.14309/ajg.0000000000000820

Patel SG, Ahnen DJ. Colorectal cancer in the young. Curr Gastroenterol Rep. 2018 28;20(4):15. 

Stoffel EM, Murphy CC. Epidemiology and mechanisms of the increasing incidence of colon and rectal cancers in young adults. Gastroenterology. 2020;158(2):341-353.