European guidelines on colorectal cancer screening and diagnosis

Should low-dose aspirin vs no low-dose aspirin be used for primary prevention of colorectal cancer in average risk adults?

The recommendation to use low-dose aspirin in adults aged 50 to 70 years at average risk for primary prevention of colorectal cancer for at least 10 years is based on a balance of benefits and risks, with a conditional recommendation due to low certainty of evidence. Low-dose aspirin (75-100 mg) is widely accessible in the EU Member States, has negligible costs, and is likely to be acceptable to patients and healthcare providers. There is minimal uncertainty in patient values, as cancer prevention is a common priority in this population. However, the low certainty of evidence is supporting the intervention necessitates shared decision-making to tailor the recommendation to individual circumstances. This approach reflects a cautious stance, ensuring potential benefits outweigh risks while addressing variability in patient preferences and risk factors.

The benefits of using aspirin are long-term and expected to be higher in those who start at the younger age of the 50- to 70-year-old age group. The reviewed studies have shown that starting aspirin at an older age was not associated with a lower risk of colorectal cancer.

The evidence suggests that there is an association between cardiovascular disease (e.g., myocardial infarction, ischaemic stroke and transient ischaemic attack) and long-term low-dose aspirin use. Moreover, people at higher baseline risk of cardiovascular diseases taking aspirin are likely to achieve higher absolute benefits (in terms of cardiovascular risk reduction). This may reflect an additional benefit for people between the ages of 50-70 aiming to prevent colorectal cancer.

This recommendation may not apply to people who are already taking antiplatelet agents or anticoagulants for other reasons, nor to those with an elevated bleeding risk (e.g., a prior history of gastrointestinal bleeding or ulcers), because they are at greater risk of harm.

Resources are required to implement the recommendation, e.g., clinician consultation and decision aids/supporting tools, which need to be provided.

To follow this recommendation, people should be fully informed and shared decision-making (between clinician and patient) will be required. The side effects of aspirin use need to be monitored, and the possible health harms need to be considered against its desirable effects. Furthermore, other factors must be considered, such as any existing gastrointestinal ulcers, concurrent use of anticoagulants, and renal impairment.

In addition, the risk for cardiovascular disease needs to be considered.

This recommendation applies to people 50 to 70 years of age and not beyond.

Regarding the potential interruption of aspirin for any surgical or medical procedures, and the use of gastroprotectants medications (i.e. proton pump inhibitors) the Working Group suggests reviewing high-quality recommendations and guidelines from other organizations.

Quality indicators for monitoring the implementation of this recommendation are planned for development.

Benefits and harms:

• The Working Group considered that additional observational studies (with a low risk of bias) with long term outcomes may be useful in confirming the benefits and harm estimates. This evidence could also inform about start and end ages for this recommendation, which is needed to evaluate if extrapolation to other age groups is warranted.
• Research on other potential harms from the long-term use of aspirin is needed (well-organised registry studies).
• Research to establish the impact of aspirin use on the accuracy of Fecal immunochemical test (FIT) based screening and its association with the site of possible lesions.
• Further research would be needed on which anatomic sites are targets of primary prevention practices. Some studies have shown the association between aspirin use and the detection of CRC and adenomas, but not between aspirin use and advanced serrated lesions.

Values, resources and acceptability:

• More information is needed about values regarding the longer-term outcomes of interest. Furthermore, information on the patients’ acceptability to use aspirin long-term would be useful.
• Cost-effectiveness analyses using the estimates of effect used in this EtD and including information about counselling, would be beneficial.

Implementation:

• Research about the communication and use of information in prevention interventions like this one will be helpful in understanding optimal ways of shared decision-making and counselling in this context.
• The role of aspirin in prevention of CRC in the context of effective screening programmes should further explored.