The American College of Physicians has decided to stay with 50 years as the recommended age for initiating colorectal cancer screening in asymptomatic average-risk adults, according to new clinical guidance.
The guidance, published July 31 (Ann Intern Med August 2023. 176[8]:1092-1100), conflicts with guidelines from at least four specialty societies that have set the lower screening threshold at age 45—including the American Cancer Society (CA Cancer J Clin 2018;68:250-281), the U.S. Preventive Services Task Force (USPSTF) (JAMA 2021;325[19]:1965-1977) and the U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF) (Gastroenterology 2021:162:285-299)—but is generally aligned with international guidelines (BMJ 2019;367:l5515; N Engl J Med 2018;378:1734-1740).
“The ACP guidance is disappointing,” said USMSTF co-author Aasma Shaukat, MD, MPH, the Robert M. and Mary H. Glickman Professor of Medicine and director of outcomes research in gastroenterology and hepatology at NYU Grossman School of Medicine, in New York City. “It undermines our effort to curb the rising incidence of CRC among individuals younger than 50. It also causes confusion among patients and payors, which detracts from our goal of achieving high screening uptake.”
Evidence shows these cancers are detected at advanced stages (JAMA 2019;321[19]:1933-1934), Dr. Shaukat said. Starting screening at 45 can reduce cancer diagnosis and deaths by detecting precancerous lesions or cancer that may have been growing for years but likely would not be detected until CRC screening at age 50 (JAMA Netw Open 2020;3[1]:e1920407).
Key Points of New ACP Guidance
The ACP’s new guidance—based on a critical review of existing clinical guidelines, evidence reviews and modeling studies—applies to people at average risk for CRC, not to those with long-standing inflammatory bowel disease or a family history of CRC.
The guidance recommends that clinicians do the following:
- Start screening for CRC in asymptomatic average-risk adults at age 50 years.
- Consider not screening asymptomatic average-risk adults between the ages of 45 and 49 years, and discuss the uncertainty regarding benefits and harms of screening in this group.
- Stop screening for CRC in asymptomatic average-risk adults older than 75 years or in asymptomatic average-risk adults with a life expectancy of 10 years or less.
- Select a screening test for CRC in consultation with patients based on a discussion of benefits, harms, costs, availability, frequency, and patient values and preferences.
- Choose among a fecal immunochemical test (FIT) or high-sensitivity guaiac fecal occult blood test (FOBT) every two years, colonoscopy every 10 years, or flexible sigmoidoscopy every 10 years plus FIT every two years as a screening test.
- Avoid use of stool DNA, CT colonography, capsule endoscopy, urine or serum screening tests.
Rationale for Screening at Age 50
Carolyn Crandall, MD, the chair of the ACP Clinical Guidelines Committee and a professor of medicine at the University of California, Los Angeles’ David Geffen School of Medicine, said the ACP acknowledges that CRC has been increasing among adults aged 45 to 49, but emphasized the incidence is still very low: 35.1 cases per 100,000 people aged 45 to 49 compared with 71.9 cases per 100,000 adults aged 50 to 64 and 128.9 cases in those aged 65 to 74 years (Dig Dis Sci 2022;67:4086-4091).
The group also was concerned that the USPSTF based its guidelines on statistical modeling for starting screening at age 45 rather than 50 (Agency for Healthcare Research and Quality [US]; 2021 May. Report No.: 20-05271-EF-2; PMID: 34097370), and not on direct trial evidence, Dr. Crandall said. “Assumptions and parameters used in the modeling are likely to overestimate the benefits, which is a limitation.”
In the USPSTF modeling, the earlier screening threshold yielded more life-years gained—22 to 27 per 1,000 screened, or eight to 10 life-days gained per person—and prevented a small number of CRC cases and deaths. But it also increased the number of colonoscopies and colonoscopy-related complications.
“The ACP Clinical Guidelines Committee wants to prioritize direct evidence as much as possible. We want to have critical evidence that screening for CRC is going to be beneficial. In the case of average-risk adults between 45 and 49 years old, that evidence is not present,” Dr. Crandall said in an interview with Gastroenterology & Endoscopy News. “The small benefit you might obtain from screening, versus the risks for additional harms, will cancel each other out.”
Conflicting Studies Cloud Clarity
In addition, the ACP noted that no studies of effectiveness and harms focused on patients younger than 50, sensitivity and specificity data for screening tests in younger adults exist mainly for adenomas and not cancers, and the accuracy of these tests in younger versus older age groups is unknown (although the predictive value is presumed to be lower). The ACP’s reason for excluding stool DNA (Cologuard, Exact Sciences), CT colonography, capsule endoscopy, and serum and urine tests is a lack of studies of their effectiveness. For stool DNA, Dr. Crandall said, an added concern is the test’s low specificity for CRC.
Thomas Imperiale, MD, the Lawrence Lumeng Professor of Gastroenterology and Hepatology at Indiana University School of Medicine, in Indianapolis, and principal investigator of Exact Sciences’ DeeP-C study, which led to the approval of the stool DNA test, commented on the ACP’s recommendation against using the test for screening, in any age group. “The ACP wants to see controlled evidence of a reduction in CRC incidence, mortality or both. Such information does not yet exist for Cologuard. So, using its more restrictive criteria, the ACP’s position is understandable. However, just about every other guideline organization disagrees with its position. In its rigor, the ACP is being very specific but not very sensitive regarding CRC screening.”
Dr. Shaukat also was concerned about the recommended protocol for noninvasive tests. “It is unclear why the guidance recommended biennial FOBT and FIT, given that we also have strong evidence from a randomized clinical trial done in the U.S. that high-sensitivity FOBT performed annually reduces CRC mortality by 33% [N Engl J Med 2013;369:1106-1114], and real-world evidence of reduction in CRC incidence and mortality with an annual FIT-based CRC screening program [Gastroenterology 2018;155(5):1383-1391],” she said.
‘Matters of Judgment’
Dr. Crandall emphasized that the ACP uses the word “consider,” and that there is room for nuance and “matters of judgment” as appropriate. “We are saying that clinicians should discuss the uncertainty around benefits and harms with their patients and be transparent about the evidence,” she said. “These recommendations will be updated as indicated when important new evidence arises.”
—Caroline Helwick
Drs. Crandall and Imperiale reported no relevant financial disclosures. Dr. Shaukat reported financial relationships with Freenome, Iterative Heath and Motus GI.
This article is from the September 2023 print issue.