Aspirin and pancreatic cancer

July 5th, 2014

Aspirin is a great prevention pill, but can it prevent pancreatic cancer?

Aspirin is one of our best disease prevention drugs. When taken at the onset of a heart attack, it is very effective at reducing death. It is also very effective at reducing the number of future cardiovascular events among patients at risk for cerebrovascular accidents (strokes), and peripheral vascular disease even when taken in low doses (1). We know this because over the last several decades aspirin has been evaluated using the best available studies, the randomized control trial. As a result, unless they have contraindications, patients with risk factors for cardiac and cardiovascular disease are generally advised to take aspirin. Many patients can take aspirin without any side effects, but because of a low risk of side effects such as gastrointestinal bleeding, aspirin is not for everyone. More recently, investigators have used the large and expensive randomized trials designed to evaluate the role of aspirin for cardiac and cardiovascular disease to answer other questions, such as the role of aspirin in the prevention of cancer.

A question like “Does aspirin reduce the incidence of cancer in the general population” is difficult to answer both because the development of cancer is a complex process involving many risk factors that play out over many years and because it is difficult to know when or if an individual is going to develop cancer. Randomized controlled trials are generally much more effective at answering such questions than other types of studies such as observational studies. In an observational study a group of people with cancer are compared to people who do not have cancer. So if investigators find that a group of control subjects who did not develop pancreatic cancer were more likely to have regularly taken aspirin than those who developed pancreatic cancer, we cannot be sure if it was the aspirin or if it was something else about the aspirin takers that explained their reduced their chance of developing pancreatic cancer? If done well, observational studies can be very helpful at exploring hypotheses, highlighting the need for more definitive studies. Moreover, randomized controlled trials are not always the last word on a subject, particularly if the trial was originally designed to answer another question.

What do the available studies tell us about aspirin and pancreatic cancer? This question was highlighted by a recent well-conducted observational study by Risch and colleagues (2) who found that a group of control subjects similar in many respects to a group of subjects who had developed pancreatic cancer were more likely to have been regular aspirin users. Was it the aspirin that the controls took or was it something else about the controls that prevented them from developing pancreatic cancer?

The role of aspirin in cancer prevention has been examined in many other observational studies, and there are also several plausible mechanisms by which aspirin use could reduce cancer development, but the best available evidence comes from randomized trials (3). These studies show suggestive but inconclusive evidence that regular long-term aspirin use can reduce the development of pancreatic cancer. These analyses find the best evidence for aspirin’s ability to reduce the cancer development is for other cancers including the colon and rectum (4), and esophagus cancer (3), where the evidence is in agreement with observational studies (5). The available evidence is consistent with the possibility that aspirin could have effects at preventing many but not all cancers, but the evidence is inconclusive.

How come physicians are not recommending regular aspirin use to reduce the incidence of cancer? The available evidence also indicates that only those who take aspirin daily for many years (perhaps 5 years or more) are likely to see the cancer-preventing benefits. This need for long-term daily use and the small risk of complications with aspirin use have so far prevented cancer societies from recommending regular aspirin use even to prevent colorectal and esophageal cancer (where the evidence for its benefit is strongest). The evidence for aspirin’s role in preventing pancreatic cancer is suggestive, but inconclusive. Additional evidence from randomized trials is needed before aspirin is recommended to prevent pancreatic cancer.

Michael Goggins, MD
Professor of Pathology, Medicine and Oncology
Johns Hopkins Medical Institutions,
Baltimore, MD

References

1. Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, Buring J, Hennekens C, Kearney P, Meade T, Patrono C, Roncaglioni MC, Zanchetti A. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009;373:1849-1860.
2. Streicher SA, Yu H, Lu L, Kidd MS, Risch HA. Case-Control Study of Aspirin Use and Risk of Pancreatic Cancer. Cancer Epidemiol Biomarkers Prev 2014.
3. Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet 2011;377:31-41.
4. Rothwell PM, Wilson M, Elwin CE, Norrving B, Algra A, Warlow CP, Meade TW. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet 2010;376:1741-1750.
5. Algra AM, Rothwell PM. Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials. Lancet Oncol 2012;13:518-527.