Young-onset colorectal cancer: American Cancer Society issues new screening guidelines

Editor’s note: This article was initiated as part of a series of feature stories developed and written by members of the American College of Surgeons Clinical Research Program to inform Bulletin readers about research and issues that affect cancer surgeons and patients.

One of the most significant and disturbing developments in colorectal cancer (CRC) is its increasing occurrence in adults younger than 55 years old.¹ In May 2018, the American Cancer Society updated its 2008 recommendations, lowering the age to initiate screening average-risk adults to 45. The organization previously recommended beginning screening at age 50.² The new recommendation to start at age 45 is a qualified recommendation, indicating “there is clear evidence of benefit of screening but less certainty about the balance of benefits and harms or about patients’ values and preferences, which could lead to different decisions about screening.”² The decision to decrease the screening age was informed by data indicating an increasing incidence and mortality of CRC in adults age 50 years and younger.¹ Overall, the incidence and mortality of CRC is declining. However, in the subset of patients younger than 50 years old, the trend has been escalating since the 1990s. Given this increased incidence, the American Cancer Society has not only lowered the age to initiate screening, but also has recommended continued screening to age 75. Continued screening in adults ages 76 to 85 years should be individualized and, for patients older than age 85, should be discouraged. The new guidelines also emphasize offering both structural (endoscopic and radiologic) and stool-based options to increase screening.

Rationale for new recommendations

CRC continues to pose a large disease burden in the U.S. It is the third most commonly diagnosed cancer and the second leading cause of cancer death in the nation. Risk factors associated with the development of CRC include cigarette smoking, excess body weight, diets high in red and processed meats and low in fiber, alcohol consumption, and sedentary lifestyles. Adenocarcinoma of the colon and rectum typically develop from precancerous adenomatous polyps through a series of mutations. Premalignant lesions represent a time for cancer interception as they can be identified and removed with endoscopic screening. Screening also can identify early-stage colorectal cancers that can be identified and treated prior to metastasis. Many randomized controlled trials have demonstrated that screening for CRC has decreased incidence and mortality associated with the development of the disease.³

Temporal trends show that CRC incidence and mortality have been declining among adults ages 55 and older because of both reduced risk factors and increased screening. However, recent national data indicates increasing incidence in adults younger than 55 years old. The American Cancer Society’s guideline development group (GDG) was tasked with reviewing the most recent incidence and mortality data to make recommendations on CRC screening. The GDG is a multidisciplinary panel of volunteers composed of generalist clinicians, biostatisticians, epidemiologists, economists, and a patient representative. In its review, the GDG used the same data and reports as the U.S. Preventive Services Task Force (USPSTF) 2016 update, which included data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) registry, to obtain incidence and mortality data. SEER collects and publishes cancer incidence and mortality data from population-based cancer registries covering approximately one-third of the U.S. population. In addition, the GDG used a recent systematic evidence review and updated modeling to reflect the most recent SEER incidence data.

The American Cancer Society then commissioned the Cancer Intervention and Surveillance Modeling Network CRC group, including MISCAN-CRC (Microsimulation Screening Analysis Colorectal Cancer Model, Erasmus University Medical Center, Rotterdam, Netherlands, and Memorial Sloan Kettering Cancer Center, New York, NY); SimCRC (Simulation Model of Colorectal Cancer, University of Minnesota, Minneapolis, and Massachusetts General Hospital, Boston); and CRC-SPIN (Colorectal Cancer Simulation Population model for Incidence and Natural history, RAND Corporation, Santa Monica, CA).² The GDG then used the GRADE (grades of recommendations, assessment, development, and evaluation) methodology to make its recommendations. Using this most recent incidence and mortality data, the American Cancer Society recommissioned the modeling group to determine the best screening methods and intervals using the up-to-date data from SEER. These revised modeling data informed the recent decrease in age to 45 to start screening for CRC.

The SEER data demonstrated an increased incidence of CRC in adults younger than 50 years old starting in the late 1980s.¹ U.S. adults younger than 50 years old had a 51 percent increase in the incidence of CRC from 1994 to 2014 and an 11 percent increase in mortality from 2005 to 2015.² The increased incidence in adults younger than 50 was most pronounced for rectal cancer, which doubled between 1991 (2.6 of 100,000) and 2014 (5.2 of 100,000).² A cohort of adults born in the 1990s is twice as likely to develop colon cancer and four times as likely to develop rectal cancer compared with a cohort born in the 1950s.¹ This increasing incidence is not solely a result of increased detection as evidenced by the increased mortality associated with the increased incidence. The recent CRC incidence data among young white adults younger than 50 years old from the late 1980s to 2014 approached the same incidence as the U.S. African-American population. Several organizations now recommend screening African-American patients at age 45.⁴

Few randomized controlled studies evaluating the efficacy of screening for CRC have included patients younger than 50 years old. The American Cancer Society extrapolated data from these trials on safety and efficacy in modeling to make its updated recommendations. The modeling then calculated the life years gained by screening after recommissioning MISCAN and SimCRC to incorporate updated SEER data on incidence, mortality, and screening safety and efficacy in the younger than 50 years old group. This modeling demonstrated significant life years gained and an acceptable risk/benefit ratio by starting screening at age 45.

Many national organizations make recommendations on CRC screening, including the American Cancer Society, USPSTF, and the U.S. Multi-Society Task Force on Colorectal Cancer. Prior to the latest American Cancer Society recommendations, these three organizations had similar CRC screening guidelines. In general, they agreed that screening should begin at age 50 and made recommendations on both structural (colonoscopy, flexible sigmoidoscopy, and computer tomography colonography), as well as stool-based studies (high-sensitivity guaiac fecal occult blood testing [gFOBT], fecal immunochemical testing [FIT], and fecal immunochemical deoxyribonucleic acid [FIT-DNA] testing). The most recent USPSTF recommendations were published in 2016 and used similar SEER data to inform their recommendations. However, the USPSTF claimed that the data were insufficient to support screening patients younger than 50 years old and, therefore, has maintained the standard of starting screening at the age of 50.

Screening options

Because 40 percent of adults are behind on screening, the new American Cancer Society guidelines aim to increase screening by providing patients with several options.³ The society’s recommendations emphasize offering several structural and stool-based methods to increase screening. Starting at age 45, the guidelines recommend structural studies including colonoscopy, repeated every 10 years if no pathology is found; flexible sigmoidoscopy every five years; or computed tomography colonography every five years. Stool-based studies include high-sensitivity gFOBT testing annually, FIT testing annually, or FIT-DNA testing every three years. Stool-based studies are less invasive, do not require mechanical bowel preparation, and can be completed in the privacy of one’s home. These tests may be more appealing to some patients and may result in increased rates of screening. All positive, nonstructural screening tests, however, must be followed up with a colonoscopy.

At present, private insurers and the Centers for Medicare & Medicaid (CMS) have no legal obligation to provide coverage for screening adults younger than 50 years old. The USPSTF, commissioned by Congress in 1984 and composed of 16 individuals, was tasked with making recommendations for screening. Screening methods with a USPSTF grade A recommendation, based on the Affordable Care Act of 2011, do not result in any cost sharing for patients and are, therefore, covered.⁵ However, because the most recent 2016 USPSTF recommendations still call for screening starting at age 50, insurers have no obligation to cover this screening. Unless the USPSTF changes its recommendations, coverage decisions will be left up to individual health care plans. Insurers set premiums annually, and, typically, there is a one- to two-year delay before any health care plan modifies its coverage policies. Physicians should check with individual insurers before making screening recommendations to avoid overburdening their patients with the cost of screening.

The American Cancer Society is the first organization to recommend starting screening at age 45 for average-risk adults based on the increased incidence of CRC in U.S. adults younger than age 55. The reason for the increased incidence is unknown but is likely multifactorial, representing a mix of genetic and environmental influences. Further work is needed to determine the causes and decrease the incidence of CRC. Physicians and patients should engage in shared decision making regarding the type of screening to be used, but a clear emphasis in the new guidelines is to offer choices to increase screening.

References

1. Siegel RL, Fedewa SA, Anderson WF, et al. Colorectal cancer incidence patterns in the United States, 1974–2013. J Natl Cancer Inst. 2017;109(8):djw322. doi:10.1093/jnci/djw322. Available at: www.ncbi.nlm.nih.gov/pubmed/28376186. Accessed January 27, 2020.
2. 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.
3. Lin JS, Piper MA, Perdue LA, et al. Screening for colorectal cancer: Updated evidence report and systematic review for the U.S. Preventive Services Task Force. JAMA. 2016;315(23):2576-2594.
4. Rex DK, Boland CR, Dominitz JA, et al. Colorectal cancer screening: Recommendations for physicians and patients from the U.S. Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol. 2017;112(7):1016-1030.
5. Peters WR. What every colorectal surgeon should know about the new American Cancer Society’s colorectal cancer screening guidelines. Dis Colon Rectum. 2019;62(4):397-398.