Pre-diagnostic aspirin use and prostate cancer-related mortality

An article just published in Renal & Urology News states that “Men who take aspirin doses above 75 mg have a significantly reduced risk of death from prostate cancer … compared with men who do not take aspirin.”

The article is based on original research published by Flahavan et al. in the January 2014 issue of Annals of Oncology, and that original research was first presented as a poster at the annual meeting of the American Society for Clinical Oncology in mid-2013.

What this research actually does is offer data that is suggestive of a possibility (as opposed to data that actually prove that possibility).

The authors were able to study (retrospectively) the pre-diagnostic use of no aspirin, low-dose aspirin (75 mg/day or less), and higher-dose aspirin (> 75 mg/day) in a cohort of nearly 3,000 men diagnosed with prostate cancer in Ireland between 2001 and 2006 who were then followed for an average (median) period of about 5 years after diagnosis

They showed the following:

  • 2,936 men diagnosed with stage I-III prostate cancer were identified from the National Cancer Registry Ireland.
    • 1,131/2,936 men (38.5 percent) were regular aspirin users
    • 1,805/2,936 men (61.5 percent) were non-users
  • Average (median) patient follow-up was 5.5 years.
  • Aspirin use in general (i.e., at any dose) was not associated any significant effect on survival.
    • With respect to prostate cancer-specific mortality, the hazard ratio (HR) = 0.90.
    • With respect to all-cause mortality, HR = 0.98.
  • Aspirin use at doses > 75 mg/day was associated with significant effects on prostate cancer-specific mortality (HR = 0.59).
  • Aspirin use at doses ≤ 75 mg/day was not associated with significant effects on prostate cancer-specific mortality (HR = 1.01).
  • Stronger associations were evident among men with higher aspirin dosing intensity or a Gleason score > 7.

The authors conclude that:

Pre-diagnostic aspirin use, measured using objective prescription refill data, was associated with a significant reduction in prostate cancer-specific mortality in men with stage I-III prostate cancer receiving > 75 mg of aspirin.

Now this study is certainly scientifically interesting, but whether it is clinically meaningful is a whole different question because of what we really don’t know. For example:

  • What risk factors did these men have for a diagnosis of prostate cancer?
  • Why were these men taking aspirin at specific doses in the first place?
  • What other clinical conditions did they have at time of diagnosis?
  • Did they continue to take daily aspirin after diagnosis (or start to take daily aspirin after diagnosis)?
  • Is the follow-up period really sufficient to be meaningful?

The evidence for and against the use of a daily aspirin regimen in the prevention of prostate cancer and in its impact on long-term survival after diagnosis when used pre-diagnosis and post-diagnosis continues to be scientifically interesting but not — in our view — completely compelling.

If there is another really good reason for a patient to be taking a daily aspirin regimen (such as a history of stroke or certain cardiovascular problems), it is certainly possible that this may have benefits when it comes to a diagnosis of prostate cancer. However, at this time The “New” Prostate Cancer InfoLink is still not convinced that there are sufficient data to suggest a daily aspirin regimen to prevent risk for a diagnosis of prostate cancer, and that is certainly the case if we are talking about doses of aspirin > 75 mg/day because higher doses of aspirin are associated with a significant risk for a variety of gastrointestinal problems.

5 Responses


    Thanks as always for finding these interesting studies!

    I would like to believe this study has found a true effect as I have been taking “baby aspirin” (81 mg, a.k.a. low-dose aspirin) every day for many years. However, despite that impressive hazard ratio of 0.59 in the study (41% lower mortality), I’m thinking that much or all of that might be due to association with other death-reducing factors, instead of due to the aspirin use, and I’m wondering whether the authors considered those factors.

    My specific concern is that taking at least a baby aspirin daily could be a proxy for health consciousness and pro-activeness, standing, for example, for more exercise, much lower incidence of smoking (adjustment made per poster), more heart and cholesterol awareness, and use of a statin drug regularly. In other words, someone taking a baby aspirin daily would be aware of the research supporting such use (or following a doctor’s advice) and would, I think, also be likely to be aware of research on the benefits of exercise, not smoking and statins and putting that knowledge to work.

    My impression is that there is a robust association between statin use and decreased death from prostate cancer, especially if the duration has been for several years, such as for 5 years or more. In fact this site has featured at least one study about that. In other words, this overall health activity, especially statin use, might be more important than aspirin use in reducing death, or at least it might explain part of that impressive hazard ratio. I’m wondering how the authors addressed this. The poster abstract states they adjusted for “pre-diagnostic statin use”, but the Devil may be in the details.

    I’m also curious about the very short follow-up of a median of 5.5 years, which would be associated with extremely few deaths if this study were based on a US population during this time frame, but perhaps the 5-year mortality in Ireland is considerably higher, and the researchers did find statistical significance for that ratio of 0.59 for consumption of approximately a baby aspirin or more per day, suggesting that a 5.5 year follow-up in Ireland is meaningful.

    The abstract did address a plausible mechanism: “… mechanisms of aspirin have been proposed, including the inhibition of the cyclooxygenase enzymes, through which aspirin mediates both anti-platelet and anti-inflammatory activities. …” I used Celebrex, a Cox-2 inhibitor, at a substantial dose for a period of time as part of my prostate cancer program, and I had clear evidence of a favorable impact on my PSA, which is consistent with some research studies. A real effect for aspirin strikes me as plausible.

  2. Looks like clutching at straws to me. The aspirin use was objectively established by prescription before cancer diagnosis … as you say, “Why?” Presumably, getting a cancer diagnosis isn’t going to change pre-existing conditions but only increase the variety of medications one may be prescribed! And one is castigated for liking vitamin C!

    Bah humbug?


    I still am thinking along the line of my earlier response, but the lack of impact of higher dose aspirin (> 75 mg/day) — hazard ratio just 0.98 — seems inconsistent with that explanation.


    The poster indicated these potentially influential factors were taken into account by adjustment, yet we are looking at raw hazard ratios based on all patients in the higher dose aspirin group versus the no-aspirin group. I could more comfortably accept adjustment if the results were a multi-factor regression analysis, but they are not presented that way.

    Perhaps pre-diagnosis statin use and smoking were negligible in the population, or nearly equal, but that does not seem likely.

    I’m puzzled.

  5. Most medics are not mathematicians of any status beyond high or junior school. Most statistics in medicine, as in politics, are little more than smoke and mirrors.

    The basic ideas were developed for a serious life purpose: gambling. The field of “knowledge” got the name Statistics when civil servants hijacked the math (US)/maths (UK) in order to speak unto their political masters “with authority,” that’s to say, in a form of mumbo jumbo (numbers) so the politicians can say it’s what they’re doing anyway, or it’s in line with this or that policy, or at least with a policy aspiration. Smoke and mirrors.

    Some decades ago, aspirin was being proclaimed as a (safe) drug to stave off cardiovascular problems (such as premature death). Mind you, it could have GI implications. They knew that, even way back then. Indeed I heard of a pharmaceutical chemist ask to choose between two white crystalline powders — aspirin or heroin. He recommended the company develop the latter. Those were the days!

    Why, oh why do otherwise apparently intelligent professional people keep on earnestly exhorting us ordinary folk to poison ourselves!

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