Does regular aspirin therapy improve survival of prostate cancer patients?

An open-access, full text article in the April issue of the Journal of Urology addresses long-standing questions about the impact of regular aspirin use on the long-term outcomes of men diagnosed with and treated for prostate cancer.

Assayag et al. used data from the UK’s National Cancer Data Repository, Clinical Practice Research Datalink, and associated databases to identify a very large cohort of men diagnosed with non-metastatic prostate cancer between 1998 and 2009, and followed until 2012. By using standard statistical modeling techniques, they were able to  estimate adjusted hazard ratios (aHRs) for mortality outcomes associated with the post-diagnostic use of aspirin over time along with the effects of pre-diagnostic aspirin use as well.

Here is a summary of their findings:

  • The total study cohort included 11,779 prostate cancer patients (all non-metastatic at initial diagnosis).
  • The average (mean) age at diagnosis was 71.3 ± 8.8 years.
  • Patients were followed for an average (mean) of 5.4 ± 2.9 years.
  • During the follow-up period there were
    • 1,793 cases of prostate cancer-specific mortality
    • 3,502 cases of death from any cause
  • Post-diagnostic use of aspirin was associated with an increased risk of
    • Prostate cancer-specific mortality (aHR = 1.46)
    • All-cause mortality (aHR = 1.37)
  • For patients who started aspirin therapy after their initial diagnosis with prostate cancer
    • The increase in risk for prostate cancer-specific mortality was 84 percent (aHR = 1.84).
    • The increase in risk for all-cause mortality was 70 percent (aHR = 1.70).
  • For patients who had started aspirin therapy before their initial diagnosis with prostate cancer
    • There was no evidence of increase in risk for prostate cancer-specific mortality (aHR= 0.97).
    • There was also no evidence of increase in risk for all-cause mortality (aHR = 0.98).
  • There was no evidence overall of a duration-response relationship between the use of aspirin and the risk of prostate cancer-specific mortality; however,
    • The highest risk for prostate cancer-specific mortality was observed with post-diagnostic use of aspirin for < 12 months (aHR = 1.61).
    • The highest risk for all-cause mortality was also observed with post-diagnostic use of aspirin for < 12 months (aHR = 1.49).

The authors conclude that:

The post-diagnostic use of aspirin is not associated with a decreased risk of prostate cancer outcomes. Increased risks were restricted to patients initiating these drugs after their diagnosis, suggesting a noncausal association [between the regular use of aspirin and mortality in men with prostate cancer].

While this may be the largest and most sophisticated attempt to address whether an anti-inflammatory agent like aspirin has any impact on the long-term outcomes of men with prostate cancer, the authors are very careful to point out the limitations of this study — starting with the fact that the follow-up period was relatively short, that a national screening program for prostate cancer has never been implemented in the UK, and that, perhaps consequently, the average age at diagnosis and the clinical stage of the patients at diagnosis may differ significantly from those of populations in which widespread screening programs had been initiated in the 1990s (e.g., the USA and parts of Austria).

On the other hand, there does seem to be a clear message to patients in these study results: unless there is some other good reason to initiate aspirin therapy after a diagnosis of prostate cancer, initiation of this type of treatment post-diagnosis or post-treatment seems highly unlikely to lead to any beneficial increase in prostate cancer-specific or overall survival, and may well lower these.

2 Responses

  1. Not satisfied with the data on aspirin and PC mortality

    I’m glad the researchers looked at this, and thank you Sitemaster for posting it.

    However, the methodology strikes me as pretty shaky. After all, aspirin is available over the counter, as well as, apparently, by prescription in the UK, which was the source of the aspirin use data. The authors are aware of this limitation and address it with these words in the Discussion section that deals with limitations of the study:

    “… However, it is unknown whether prescriptions were actually filled and if patients fully complied with the treatment regimen. Such misclassification of exposure would have biased the results towards the null. Furthermore, aspirin is available over-the-counter, it is possible that users were misclassified as nonusers. However, it is reasonable to assume that patients with chronic cardiovascular conditions are likely those to be the long-term users of aspirin ….”

    One of the key results is really puzzling and contrary to our knowledge of prostate cancer mortality, which is that non-prostate c ncer-specific mortality far outstrips prostate cancer-specific mortality as a cause of death for prostate cancer patients. Yet look at this, from the article above:

    “During the follow-up period there were

    — 1,793 cases of prostate cancer-specific mortality
    — 3,502 cases of death from any cause.”

    That’s far too few “any cause” cases to match what we see almost universally elsewhere. Any thoughts?

    I’m also concerned that the scope for benefit (or harm) from aspirin is likely relatively small in the overall landscape of prostate cancer, small enough that a much larger and better defined study would be needed to tease out that benefit (or harm). We have a similar situation in looking at overall survival of prostate cancer patients, where competing causes of death are so much more prominent that the benefit of prostate cancer therapy is dwarfed, even though some of us dearly need that benefit, and, because prostate cancer is so common, we will have about 30,000 deaths a year these days.

    The overall thought though is that men who begin taking aspirin after diagnosis of prostate cancer are likely to be in poorer shape overall, which correlates with a more serious case of prostate cancer. Therefore, I suspect that association, not cause, is responsible for whatever link we are seeing here, as mentioned by Sitemaster and the authors.

  2. Among the several vexatious questions raised by these study results, in addition to those already pointed out by the sitemaster and Jim Waldenfels, is the very high death rate (15%) from prostate cancer within the mean 5.4-year follow-up, for patients who had been first diagnosed as non-metastatic. Bearing mind that non-treated, non-metastatic patients typically take several years before metastases first appear, plus an average of another 3 years before they die of the disease, this 15% seems (say I, scribbling furiously on the back of an envelope) about 300% too high.

    Possible theories might include:

    — Rotten treatment, given the long NHS waiting periods
    — Faulty initial diagnosis (many were actually already metastatic)
    — A relatively different (from other areas) genetic makeup in the UK, or in some parts of the UK, leading to more-aggressive sub-types of prostate cancer in a larger percentage of the patients than we might expect.

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