When Should Guidelines Change? A Clarion Call for Evidence Regarding the Benefits and Risks of Screening for Colorectal Cancer at Earlier Ages

Colorectal cancer (CRC) is a significant public health problem and a major focus of research and clinical care for gastroenterologists; thus, changes in CRC practice guidelines confer a large impact on patients, clinicians, health care systems, and insurers. Despite substantial decreases in the incidence of CRC over the last 30 years, cancers of the colon and rectum are still the second leading cause of cancer death in many countries. In the United States, for example, the lifetime risk of CRC is 4.7%, it accounts for >8% of all cancer mortality, and in 2018 there will be an estimated 140,250 incident CRC cases and 50,630 CRC deaths.^1,2 Endoscopic and fecal-based screening tests markedly reduce the risk of cancer and cancer death.³ However, only 62.6% of adults over the age of 50 received either a fecal test in the past year, sigmoidoscopy in the past 5 years, or a colonoscopy in the past 10 years.⁴ In addition, demonstrated disparities in colorectal mortality by race (eg, African Americans) and sex raise questions regarding whom to screen, when to screen, and how to screen most effectively.^3,5

Guidelines for CRC screening differ somewhat, although there has been a consensus on initiating regular CRC screenings at age 50, among average risk people (Table 1).^6–11 The same guidelines also recommend ages to stop routine screening and ages after which point additional screening should be individualized based on preference, risk factors, and estimated life expectancy.

Table 1.

Screening Guidelines

Group	Age to Begin Routine Screening (y)	Age to Consult with Physician on Continued Screening (y)	Age to Sbottom Routine Screening (y)
US Multi-Society Task Force on Colorectal Cancer	50a	75	85
National Comprehensive Cancer Network	50	76	85
American College of Physicians	50b	—	75
European Council	50	—	75
American Cancer Society	45	76	86
US Preventative Services Task Force	50	76	86

^aAt 45 years for African Americans.

^bAt 40 years for high-risk adults.

In May 2018, this consensus changed when the American Cancer Society published revised guidelines and provided a qualified recommendation for starting screening for average risk adults at age 45.¹² It was a “qualified” rather than a “strong” recommendation because there is compelling evidence of screening benefits, but fewer data regarding the benefit-to-harm ratio and patient preferences, including by modality.^12–14 Given this relative lack of empirical evidence on screening effectiveness in patients under the age of 50, experts have relied largely on modeling analyses. The modeling team working with the US Preventative Services Task Force, for example, suggested that, for most model screening strategies, beginning at age 45 may provide a favorable balance between life years gained and the cost/risks of more screening.¹⁵ In the end, they did not change their 2016 recommendations, citing a lack of empirical evidence.^12,15 The American Cancer Society, in addition to such modeling studies, noted that, although CRC has been decreasing steadily over the past 2 decades among persons >50 years of age, there has been about a 51% relative increase (although a low absolute incidence) among those <50 years of age¹²; other investigators have questioned whether these changes are partially related to increased detection.¹⁶ Additional studies have shown a similar prevalence of large polyps among adults between 45 and 49 and 50 and 54 years of age,^12,17 although the extent to which their earlier removal impacts important endpoints is unknown, as well as whether younger patients were from higher risk populations.

The initial responses to the American Cancer Society’s recommendation change have been measured, with calls for more evidence on both potential benefits and harms for strategies using varied ages and modalities. Concerns for lowering the screening age centered on appropriate balancing of both risk/benefit and cost/benefit. For example, Bretthauer et al¹⁸ estimated that, assuming screening tests decreased CRC mortality by 50% and that screening cost $250 per person (based on a mix of expensive and inexpensive screening modalities), preventing 900 CRC deaths among persons 45 to 49 years of age would have cost $5.5 billion in 2017. The Centers for Disease Control and Prevention, in an electronic communication from Dr Lisa Richardson, the Director of Cancer Prevention and Control, noted that,

The Centers for Disease Control and Prevention (CDC) supports use of the U.S. Preventive Services Task Force recommendation to begin screening for colorectal cancer (CRC) at age 50 years. The majority of new cases of colorectal cancer—about 90%, occur in people who are age 50 years or older. Many adults are not currently benefitting from CRC screening, a potential life-saving intervention. While nearly 80% of adults age 65 to 75 years were up to date with colorectal cancer screening in 2016, less than two-thirds of adults age 50 to 64 were up to date. Thus, it is important for CDC-funded programs to focus their limited resources on reaching this group for screening and early detection. In addition, increasing awareness of the importance of CRC screening remains important. CDC supports educating providers and all adults, regardless of age, about the importance of knowing their family history of colorectal and other cancers, and recognizing the symptoms of CRC to seek timely medical care. Moreover, collaborating with partners to increase CRC screening among uninsured, underinsured, low-income, rural, racial and ethnic minorities, and other populations that have disproportionately high burdens of colorectal cancer and lower rates of screening is essential.

A joint electronic communication from the Multi-Society Task Force (MSTF) on Colorectal Cancer, a consortium representing the American Gastroenterological Association, The American College of Gastroenterology, and the American Society of Gastrointestinal Endoscopy, stated that,

The MSTF has previously recommended that colorectal cancer screening for average-risk persons (persons who do not have a family history of colorectal cancer in a first-degree relative) begin at age 45 years in African Americans and age 50 in other groups. The MSTF has reviewed the recent recommendation from the American Cancer Society (ACS) to lower the age to begin screening from 50 to 45 years in all Americans. This change was a qualified recommendation based largely on a modeling study utilizing updated data on the incidence of colorectal cancer in younger people. Evidence from screening studies to support lowering the screening age is very limited at this time. Based on the modeling study used to support the ACS recommendation, the MSTF recognizes that lowering the screening age to 45 may improve early detection and prevention of CRC. The MSTF expects the new ACS recommendation to stimulate investigation that will clarify the benefits and risks of earlier screening. As the MSTF has previously noted and discussed, rates of colorectal cancer are increasing in Americans down to age 20 years. Beginning screening at 45 years addresses only part of the increasing risk of colorectal cancer in young persons. For all persons under 50 years, it remains critical to promptly assess symptoms consistent with colorectal cancer. In particular, rectal bleeding and unexplained iron deficiency anemia have substantial predictive value for colorectal cancer and should be thoroughly evaluated.

Differences in opinion provide key opportunities for research, which, in turns, develops the evidence needed for informed decision making; as the specialty’s leading international journal in gastroenterology, we look forward to vigorous discussions and new investigations regarding when to start screening, when to stop, and how best to better match risk of disease, potential screening benefits, known harms and patient preferences. Such evidence can inform greater consensus regarding when to start and stop CRC screening in different settings.