Back in 2007, the U.S. Preventive Services Task Force (USPSTF) proposed that aspirin should not be used routinely to prevent colorectal cancer (CRC). However, in the latest guidelines published in September 2015, the task force proposed that low-dose aspirin (81 mg/d in the United States) could prevent chronic diseases, including CRC.
Among those in the age group 50 to 59 years with a risk of cardiovascular disease (CVD) of more than 10% in the next 10 years, the recommendation grade is B, meaning that a moderate to high benefit exists with high or moderate certainty. In the age group of 60 to 69 years, with more than 10% risk of CVD in the next 10 years, the recommended grade is C, meaning that there is at least a moderate certainty of a mild benefit.
The importance and rationale for the guideline, the risks and benefits of long-term aspirin use, how the effectiveness of aspirin and monitoring for CRC risk reduction can be explored from different population perspectives, and future developments in aspirin chemoprevention are reviewed by Chan of Harvard Medical School and Ladabaum of Stanford University School of Medicine in an article published online in the recent Gastroenterology.
The Importance and Rationale of USPSTF Guidelines
In addition to the preventive effect of tamoxifen on breast cancer, aspirin was the 1st cancer preventive agent recommended by the working group.
The Task Force was established in 1984 as the unit responsible for evidence-based guideline development in the management of chronic disease in the United States. Since 1998, it has conducted high-quality peer review of guidelines with the support of the Agency for Healthcare Research and Quality, and has had a significant impact in clinical practice.
The guidelines acknowledge the numerous lines of evidence for aspirin in the prevention of CRC. Within the past few decades, epidemiologic data have shown that aspirin is associated with a reduced risk of colorectal adenoma and cancer, but there are still relatively few randomized controlled trials (RCTs) that directly support this conclusion.
Although neither the larger clinical studies Women’s Health Study (WHS) nor the Colorectal Adenoma/Cancer Prevention Project 2 (CAPP2) confirmed the association of aspirin with risk of CRC, five recent independent RCTs from the United States, Europe, and Japan confirmed the ability of aspirin to reduce the recurrence rate of CRC. In addition, extended follow-up of many RCTs has confirmed the preventive effect of aspirin on CRC.
Benefits and risks of aspirin as primary prevention
The guideline does not specify the exact dose of aspirin for chemoprevention of CRC. The current view is that, on the one hand, reducing the risk of CRC may have an additional benefit only for the prevention of CVD (nonfatal myocardial infarction and coronary events) and, on the other hand, the benefits and risks of long-term use need to be considered in combination. To this end, the authors review the important clinical applications of aspirin and their impact on life expectancy.
The authors screened the following important findings from USPSTF-approved systematic reviews.
1. a mild, significant reduction in overall mortality over 10 years
2. a mild reduction in CVD events over 5 years, but not in CVD mortality.
3. no reduction in overall cancer mortality in studies with a follow-up period shorter than 10 years
4. reduction in CRC mortality after long-term follow-up.
5. reduction in CRC incidence after a 10-year follow-up period
6. increased risk of gastrointestinal bleeding, but not of fatal bleeding
7. an increased propensity for risk of hemorrhagic stroke or other intracranial hemorrhage.
In addition, the guidelines point out the effect of low-dose aspirin (<100 mg/d) on life years and quality-adjusted life years (QALYs). These results shed light on the age group that would benefit from aspirin chemoprevention.
Aspirin chemoprevention for CRC: a complement and alternative to surveillance?
The results of the WHS study show that aspirin can still prevent CRC when monitored over time. However, it is not clear how surveillance and chemoprevention interact. What is the combined benefit of aspirin and surveillance? Can aspirin chemoprevention reduce monitoring requirements? How can surveillance be implemented in populations taking low-dose aspirin?
The guideline provides recommendations on these questions. Several RCTs have demonstrated that fecal occult blood test surveillance reduces CRC mortality and that sigmoidoscopic surveillance reduces its incidence and mortality. Observational studies have confirmed that colonoscopic polypectomy may reduce CRC mortality even more significantly.
However, the preventive effect of aspirin and surveillance is closely related to patient compliance. Studies have shown that compliance with aspirin is 85% in the first year of administration, but decreases to 50%-83% after 3 to 5 years; more than one-third of patients in the United States do not complete CRC surveillance as required. The interaction between the two in terms of adherence remains to be confirmed by further studies.
Although aspirin compliance is higher than monitoring, it is not yet a complete substitute for monitoring, and the substitution depends on its significance independent of the monitoring aspect. Some studies have shown a higher benefit of aspirin in the proximal colon, implying that it may be a useful complement to endoscopy (which is more significant for distal CRC). It is important to note that the proposition of aspirin in relation to surveillance is only applicable in countries where it is highly recommended and CRC surveillance is widely available.
Future perspectives
At present, the working group acknowledges the positive role of aspirin in CRC chemoprevention and its additional role in reducing CVD risk in specific populations, and the potential for further benefit of long-term low-dose aspirin application on top of CRC surveillance. However, the working group did not endorse the use of aspirin for cancer prevention purposes.
First, studies are needed to confirm the preventive effects of aspirin for cancers other than CRC, such as esophageal, breast, prostate, and lung cancers; second, more comprehensive studies on the effects of aspirin and surveillance on CRC incidence and mortality are needed; and third, better risk assessment tools for CRC, other cancers, and gastrointestinal bleeding are needed.
In summary, using this guideline as a basis, clinicians should use a risk assessment tool to predict 10-year CVD risk, such as the Framingham Risk Score. For those at more than 10% risk, 81 mg of aspirin daily for more than 10 years may also be recommended for CRC prevention in people aged 50 to 59 and 60 to 69 years. For those not taking aspirin, the same CRC monitoring should still be given.