Aspirin use and risk for lethal prostate cancer

New data derived from the Physicans’ Health Study have suggested that there is an association between regular aspirin use and avoidance of risk for lethal forms of prostate cancer. (We should note that these new data are from the formal publication of data originally presented by Allard et al. at the Geniturinary Cancers Symposium in early 2016.)

The new paper by Downer et al. in European Urology was designed to elicit long-term follow-up data related to the regular use of aspirin tablets (> 3× a week) and the effects on

  • Risk for lethal prostate cancer
  • Survival after diagnosis with prostate cancer

In interpreting the data from this long-term analysis (at up to 34 years of follow-up), some caution has to be exercised because of the way the study was carried out.

  • In 1981/2 at total of 22,071 healthy, male physician here in the USA were randomized to treatment with
    • Aspirin
    • β-Carotene
    • Aspirin and β-carotene
    • A placebo
  • These patients were then followed for 6 or 7 years until 1988, and after that initial trial was completed, …
  • The participants were then asked to complete annual questions asking about
    • Aspirin use
    • Cancer diagnosis
    • Cancer outcomes

If the patients were diagnosed with prostate cancer, they were followed until 2015 (33 or 34 years of follow-up in total); if they were not diagnosed with prostate cancer, they may only have been followed until 2009 (27 or 28 years of follow-up in total). In other words, after the first 7 or 8 years of the trial, it was no longer a randomized trial, it was simply an exercise in epidemiological monitoring, and so all that the data can give us is suggestions about possibilities (i.e., one or more hypotheses) as opposed to actual actionable clinical guidance.

What Downer et al. have been able to show from their study is the following:

  • 502/22,071 men  (2.3 percent) developed lethal prostate cancer between 1981 and 2009.
  • Compared to the men who had never used regular aspirin treatment,
    • Men who were current aspirin users had a reduced risk for lethal prostate cancer (hazard ratio [HR] = 0.68).
    • Men who were past aspirin users also had a reduced risk for lethal prostate cancer (HR = 0.54).
  • 407/3,277 men diagnosed with non-lethal prostate cancer (12.4 percent) developed lethal prostate cancer by 2015.
  • Compared to the men who never used regular aspirin treatment after diagnosis of non-lethal prostate cancer,
    • Men who were current aspirin users post-diagnosis had a reduced risk for development of lethal prostate cancer (HR = 0.68).
    • Men who were current aspirin users post-diagnosis had a reduced risk overall mortality (HR = 0.72).

However, as the authors are careful to note,

We could not assess aspirin dose, and inconsistencies were observed in some sensitivity analyses.

From a patient perspective, the authors conclude that

… taking aspirin was associated with a lower risk of lethal prostate cancer, and taking it after diagnosis may help to prevent prostate cancer from becoming fatal.

They also conclude that their data would justify a randomized clinical trial to confirm or refute the findings from their study.

These conclusions are both reasonable. However, it should be noted that:

  • Regular aspirin use (and particularly the regular use of aspirin in doses of 325 mg/day or higher) comes with a significant risk for gastric ulcers and gastric bleeding which can have severe consequences in and of itself.
  • The chances that we could conduct a 30-year-long, randomized clinical trial to see if taking (say) low-dose, enteric-coated aspirin could reduce risk prostate cancer today is probably vanishingly small (based on cost alone).

Perhaps the best way for patients to look at these data is that if your doctors already think you might benefit from taking low-dose aspirin on a daily basis for any other reason, it may help to minimize your risk for lethal prostate cancer too, but if you have no other indication for regular use of aspirin, then starting to take it just in order to avoid risk for lethal prostate cancer is still not yet justified by level 1 data, and does come with risk for other side effects and potential complications.

4 Responses

  1. A Molecular Approach to Aspirin Use for the Half Of American Prostate Cancer Patients with TMPRSS2:ERG Gene Fusion

    Thanks as always for providing these interesting articles. This one immediately reminded me of key expert commentary I recently viewed.

    Aspirin use was addressed by Dr. Charles “Snuffy” Myers, MD, at the 2016 Conference on Prostate Cancer (PCRI/UsToo) in September 2016 in Los Angeles. Dr. Myers, as many of us know, has a practice dedicated to prostate cancer that cares for many patients with advanced and challenging disease. (He is preparing to retire.) He was responding to a post-presentation question by Dr. Mark Moyad (Disc 2, about 2:14) on his recommendation for aspirin use for prostate cancer patients, which he had addressed briefly (Disc 2, about 2:04) in his talk.

    His main points were:

    — Aspirin is the primary medication to target prostate cancer that features fusion of the genes TMPRSS2 and ERG, and it is effective. That’s important because TMPRSS2/ERG gene fusion makes prostate cancer more likely to progress and is associated with lethal prostate cancer. The combination of TMPRSS2/ERG gene fusion and loss of PTEN gene expression is a particularly lethal combination, and aspirin and metformin are the best drugs for both of those.

    — Dr. Myers is “very nervous” about using aspirin for prostate cancer patients based on finding that a dozen of his patients had become iron deficient from using baby aspirin over the past year. Therefore, he does a molecular test for TMPRSS2/ERG gene fusion, and, if positive, has patients on aspirin but with regular monitoring of iron levels.

    — He feels that patients intending to go on active surveillance should first be screened for TMPRSS2/ERG gene fusion and take baby aspirin if they have such gene fusion. That makes a lot of sense as the fusion is so common among American men and as obesity is a common issue that amps up the risk (see below). (Research suggests rather striking differences among ethnic groups.) Apparently, based on his mention of baby aspirin, a low dose is all that is needed. Dr. Myers likely is basing his approach on a body of published research as well as on his own clinical experience, boosted by computer review of his electronic patient records.

    Here is a link to a paper that addresses this gene fusion and aspirin use. I have not read the full paper, which is linked, but the abstract reports a 37% reduction in incidence of this fusion in aspirin users in this fairly loose case control study of radical prostatectomy patients. Here’s a link to an attention-catching abstract that associates this gene fusion plus obesity with lethal prostate cancer, also with a link to the complete paper. It’s an impressive example of research enabling us to tailor therapy to personal situations, and also enabling us to take a more refined view of population studies like the subject paper.

    I took baby aspirin for many years, for both cardiovascular and prostate cancer benefits, up to a few years ago. Though I felt I tolerated it very well, I stopped because my prostate cancer appeared to be in profound remission and potentially cured, as is still the case, and because my gastroenterologist suggested that I limit my use of NSAIDs based on what he had seen during a colonoscopy. I never had a problem with iron levels. Of course, some of us will choose to take aspirin for its cardiovascular benefits even if we do not have the gene fusion problem.

  2. Hi Mike,

    You probably know this already, but the RCT on aspirin and cancer is now underway. It is a large study out of clinical trials group in London, UK. It is called the “add-aspirin” study. Details can be found here

  3. Richard:

    Yes. I am aware of the “Add-Aspirin” trial, but it is only going to deal with the question of whether taking aspirin can prevent recurrence of prostate cancer and can actually improve mortality rates among men already diagnosed with and treated for prostate cancer, so it is only addressing one of the several questions raised by the Physicians Health Study.

    I also have my doubts about whether the proposed 10-year follow-up will be long enough to demonstrate an overall survival benefit.

  4. Aspirin is an inhibitor of COX1 and COX2 and therefore is indirectly an inhibitor of angiogenesis. It is well known that angiogenesis is a hallmark of tumor growth and progression, in solid and hematological malignancies. In view of the above the results are logical and not surprising.

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