Yes, but individualize it
By Sonia S. Kupfer, MD
Colorectal cancer (CRC) is one of the top three causes of cancer and cancer death worldwide with an alarming rise in younger adults. Preventive strategies including screening, chemoprevention, and risk factor modification are important to reduce overall CRC burden. Aspirin, which is cheap and readily available, is supported for CRC chemoprevention by multiple lines of strong evidence. Recent AGA practice guidelines recommend low-dose aspirin chemoprevention in individuals at average CRC risk who are younger than 70 years with a life expectancy of at least 10 years, have a 10-year cardiovascular disease risk of at least 10% and are not at high risk for bleeding.1 This advice diverges from the most recent U.S. Preventive Services Task Force–proposed guidelines2 that reverse the 2016 USPSTF recommendation for aspirin CRC chemoprevention (and primary prevention of cardiovascular disease) based on uncertainty of net benefit over harms, especially in older individuals. In light of conflicting advice, how should we counsel our patients about aspirin use for CRC chemoprevention? In my opinion, we shouldn’t “throw the baby out with the bathwater” and should follow the AGA practice guideline to individualize aspirin chemoprevention based on balancing known benefits and risks.
Dr. Sonia S. Kupfer
As reviewed in the AGA practice guidelines1, many, but not all, randomized controlled and observational trials have shown efficacy of aspirin for reduction of CRC mortality, incidence, and adenoma recurrence. Analysis of cardiovascular prevention trials including over 14,000 mostly middle-aged people showed 33% reduction in 20-year cumulative CRC mortality. While a pooled estimate of four trials did not show reduced incidence 0-12 years after aspirin initiation, as noted in the practice guideline, three of these trials did show a 40% reduction between 10 and 19 years, a finding that is in line with results from a 20-year pooled analysis showing 24% reduction in CRC incidence by aspirin. Among Lynch syndrome patients, exposure to high-dose aspirin also significantly reduced CRC incidence in a randomized controlled trial with up to 20 years of follow-up3 highlighting that chemoprotective effects take years to manifest, and long-term follow-up in cancer chemoprevention trials is needed. Studies also have shown reduced adenoma incidence or recurrence by aspirin ranging from 17% to 51% depending on the study population, dose, and adherence. In addition to clinical trials, experimental data have demonstrated protective cellular effects of aspirin on colonic carcinogenesis, though exact mechanisms of this protective effect remain incompletely understood and are active areas of research, including in my lab. Taken together, there is a large body of evidence supporting a protective effect of aspirin on CRC mortality and colorectal neoplasia incidence most evident after 1-2 decades of follow-up.
Not all trials have shown that aspirin is chemoprotective, and, in fact, the ASPREE trial,4 that randomized over 19,000 healthy adults over the age of 70 to 100 mg aspirin or placebo, showed increased cancer mortality when the trial was stopped prematurely after 5 years. Individuals who started aspirin under age 70 appear to have continued chemoprotection as they age5 suggesting that aspirin, if it is tolerated, might not necessarily need to be stopped at a certain age. Notably, the ASPREE trial did not show increased CRC incidence, which begs the question of the biological mechanism underlying increased cancer mortality in trial participants. Beyond the findings of ASPREE, aspirin use is associated with risks of intracranial and gastrointestinal bleeding with estimated odds ratios of 1.29 and 1.59, respectively. The AGA practice guideline acknowledges these risks especially in older adults and recommends initiation of aspirin in individuals under the age of 70 who are expected to live another 10 years without bleeding risks in order to reap the benefits and minimize the risks.
