The use of low-dose aspirin by most adults aged 50 to 59 for the primary prevention of colorectal cancer is now included in the U.S. Preventive Services Task Force (USPSTF) updated draft recommendation statement, “Aspirin to Prevent Cardiovascular Disease and Cancer.”1 The release of the statement in September was widely reported by major media, including The New York Times2 and The Washington Post,3 which pointed out the statement marked the first time the USPSTF had recommended daily aspirin to prevent colorectal cancer and that it sparked diverse reactions. These reactions ranged from support and excitement about another option for colorectal cancer prevention to caution about the potential harms of aspirin use and overemphasis of the role of aspirin in preventing colorectal cancer.
“I have major concerns that the message will be, ‘I take aspirin, so I don’t need to be screened,’” said David Johnson, MD, a member of the U.S. Multi-Society Task Force on Colorectal Cancer, who was quoted in The New York Times.2 Elaborating on this and other caveats to the USPSTF draft recommendations, Dr. Johnson, Professor of Medicine and Chief of Gastroenterology at Eastern Virginia Medical School, Norfolk, and Past President of the American College of Gastroenterology, told The ASCO Post that it is “really important not to take [the USPSTF recommendation] out of context.”
“This does not subrogate the appropriate need for colonoscopy for screening, which is the best test for colon cancer prevention because we remove premalignant polyps,” Dr. Johnson stated. The recommendation concerning aspirin “doesn’t decrease the message that patients still need screening by colonoscopy for true prevention of colon cancer.” But taken out of context, “the danger would be that patients may shy away from colonoscopy,” Dr. Johnson explained.
Update of Previous Recommendations
The draft recommendations advise daily low-dose aspirin (75 to 81 mg/d) for the primary prevention of cardiovascular disease and colorectal cancer in adults aged 50 to 59 who have not been diagnosed with cardiovascular disease, but have a 10% or greater 10-year risk of cardiovascular disease, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years. Those aged 60 to 69 who have a 10% or greater 10-year risk of cardiovascular disease, and particularly those who meet the other criteria, may also benefit from daily low-dose aspirin, but the decision to do so should be made on an individual basis. The evidence was insufficient for the USPSTF to recommend daily aspirin use for adults younger than 50 or older than 70.
An explanatory document noted that the task force “found that people at increased risk of cardiovascular disease who take aspirin for at least 10 years can also reduce the likelihood of developing colorectal cancer. However, they found no direct evidence that people who are at increased risk for colorectal cancer but not cardiovascular disease would benefit overall from taking aspirin.”4
To update its 2007 recommendation concerning aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent colorectal cancer and the 2009 recommendation on aspirin to prevent cardiovascular disease events, the USPSTF reviewed four additional studies of aspirin and cardiovascular disease and several additional analyses of colorectal cancer follow-up data. “The USPSTF also relied on reviews of all-cause mortality and total cancer incidence and a comprehensive review of harms. The USPSTF then used a microstimulation model to systematically estimate the balance of benefits and harms,” according to the draft document.
“The evidence supports what the recommendation is,” Dr. Johnson said. “There are clearly a number of caveats that I think need to be registered with that recommendation, however.”
In addition to the caveat about aspirin use not supplanting colonoscopy, Dr. Johnson cited concerns about the target population, risk stratification, and the potential harms of aspirin use, particularly when combined with NSAIDs.
May Be ‘Timeline Bias’
The USPSTF recommendation “is focused on a very specific age range, which to me seems somewhat nonsensical. And there may be a timeline bias that the risk of cancer is potentially pushed back, not necessarily decreased overall, because of the limited focus on the ages that they target in this recommendation,” Dr. Johnson said.
“It doesn’t seem very helpful to target for a very narrow age range when patient life expectancy is far greater than what it used to be, “ Dr. Johnson added. “The risk for colon cancer in the average risk individual by the age of 85 is around 5.5% for males and females both. Then targeted risks go up with a variety of other factors, such as family history, smoking, and obesity,” he added.
Dr. Johnson referenced a study conducted at the Indiana University Medical Center in Indianapolis showing that the five factors most commonly associated with colorectal cancer in the published literature—age, sex, cigarette smoking, body fat, and a family history of colorectal cancer—can be used to stratify risk for colorectal cancer.5
Risk-Benefit Assessment as Starting Point
“I am for anything that will decrease colon cancer,” Dr. Johnson stressed but added that the starting point should be a risk-benefit assessment.
The Task Force did note that aspirin use in adults has potential harms, increasing the risk for gastrointestinal bleeding and hemorrhagic stroke. These harms vary with individual risk but are small in adults aged 59 and younger and small to moderate in adults aged 60 to 69, the USPSTF determined.
The assumption that the risk for harm is small “again creates a bit of a consternation for me as I look at what patients may take out of context. Because this assumes that patients don’t have any other risk factors for bleeding that they may or may not know about, and that they are not taking any other over-the-counter nonsteroidal anti-inflammatory agents,” Dr. Johnson said.
He cited a recent study using data from 10,280 patients selected from the Danish Cancer Registry and 102,800 controls. This analysis found that while long-term use of low-dose aspirin and nonaspirin NSAIDs was associated with a substantial reduction in colorectal cancer, the potential use of aspirin and NSAIDs for preventing colorectal cancer “is limited by the risk for gastrointestinal bleeding and, for most nonaspirin NSAIDs, cardiovascular risks. These potential harms will need to be balanced against the chemoprevention benefits that our results indicate,” the authors noted.6
“I do endoscopies for a living. I see 20-year-olds come in with nonsteroidal anti-inflammatory agent–related bleeding. So bleeding risk is across all ages. It may be stratified and higher in certain ages because of other cofactors, but clearly there is still an implicit risk of harm, potentially in all ages,” Dr. Johnson said.
“The decision to take medicines always needs to be balanced with complete understanding, and when you go to simulation modeling, there is a lot of danger in misapplication or misunderstanding as patients are left to their own accord, when they start seeing recommendations from a national body such as the U.S. Preventive Services Task Force,” Dr. Johnson stated.
More Is Not Better
The USPSTF draft statement on aspirin to prevent cardiovascular disease and colorectal cancer noted that a dose of about 75 mg/d, used in many of the studies the Task Force looked at, seems as effective as higher doses, but that a pragmatic approach is an 81-mg dose, which is the most commonly prescribed dose for baby aspirin in the United States.
Might some people take higher doses, thinking that would offer a greater level of protection? “Sometimes that is the patient’s perspective—a little is good; more is better. And it is hard to contain that,” Dr. Johnson said, without a discussion between the patient and health-care provider about the risks and benefits of aspirin use, both in general and for the individual patient.
Still Just a Draft
The draft recommendation for the use of aspirin for the primary prevention of colorectal cancer is not only a first for the USPSTF but runs counter to recommendations from other medical organizations. “No organizations recommend aspirin use for the primary prevention of colorectal cancer in average-risk adults,” according to the USPSTF draft recommendation statement. “The American Cancer Society recommends against the use of aspirin and other NSAIDs as a colorectal cancer prevention strategy. The American Gastroenterological Association and the National Comprehensive Cancer Network limit their recommendations to patients who are at increased risk for colorectal cancer.”
The USPSTF draft recommendation statement was open for public comments from September 15 to October 12. The final recommendations will be published in a peer-reviewed journal, but the date of publication will depend on the volume and complexity of comments received and other work process factors. ■
Disclosure: Dr. Johnson reported no potential conflicts of interest.
References
1. U.S. Preventive Services Task Force: Aspirin to prevent cardiovascular disease and cancer. Draft Recommendation Statement. Available at www.uspreventiveservicestaskforce.org. Accessed October 9, 2015.
2. Rabin RC: In a first, aspirin is recommended to fight a form of cancer. The New York Times. September 14, 2015.
3. Dennis B: Expert panel: An aspirin a day can help keep heart attacks—and cancer—away. The Washington Post. September 14, 2015.
4. U.S. Preventive Services Task Force: Understanding task force draft recommendations: Aspirin to prevent cardiovascular disease and cancer. Available at www.uspreventiveservicestaskforce.org. Accessed October 9, 2015.
5. Imperiale TF, Monahan PO, Stump TE, et al: Derivation and validation of a scoring system to stratify risk for advanced colorectal neoplasia in asymptomatic adults: A cross-sectional study. Ann Intern Med 163:339-346, 2015.
6. Friis S, Riis AH, Erichsen R, et al: Low-dose aspirin or nonsteroidal anti-inflammatory drug use and colorectal cancer risk. Ann Intern Med 163:347-355, 2015.
