Could adding an aspirin extend prostate cancer-specific survival?

There is an interesting new paper in Cancer Biology and Therapy again suggesting the possibility that men diagnosed with high-risk prostate cancer who are taking anticoagulant therapy do better than similar men who are not on anticoagulants.

We should be clear up front that this study does not prove this idea. It simply provides enough data to consider whether the hypothesis is worth testing … and this would certainly not be a difficult hypothesis to test.

The idea that anticoagulant use may improve treatment outcomes in men being treated for prostate cancer is not original. However, there are very few specific data on the subject, so Jacobs et al. set out to generate additional data based on a series of patients treated at the University of Texas Southwestern Medical Center between 2005 and 2008.

They started from the idea that anticoagulant therapy might be able to extend freedom from biochemical failure (FFBF) and overall survival (OS) when administered along with radiotherapy in men initially diagnosed with high-risk prostate cancer.

Here is what they found:

  • 74 high-risk patients were treated with radiotherapy at their center between 2005 and 2008.
    • 43/74 patients (58 percent) were on anticoagulant therapy.
    • Anticoagulants included aspirin (95.6 percent), clopidogrel (17.8 percent), warfarin (20 percent), and multiple anti-coagulants (31.1 percent).
  • Average (median) patient follow-up was 56.6 months.
  • FFBF at 5 years was evident in
    • 80 percent of men taking any anticoagulant
    • 62 percent in men taking no anticoagulant
      • This difference was statistically significant (P = 0.003)
    • 84 percent in men taking aspirin
    • 65 percent in men not taking aspirin
      • This difference was statistically significant (P = 0.008).
  • Distant metastasis was evident in
    • 12.2 percent of men taking aspirin
    • 26.7 percent of men not taking aspirin
      • This difference was statistically significant (P = 0.039).
  • 5-year OS among men with Gleason grades of  9-10 was
    • 88 percent among men taking aspirin
    • 37 percent among men not taking aspirin
      • This difference was statistically significant (P = 0.032).
      • This difference remained significant on multivariable analysis (P < 0.05).

Jacobs et al. conclude that use of anticoagulant therapy

was associated with a FFBF benefit in high-risk [prostate cancer] which translated into an OS benefit in the highest risk [prostate cancer] patients with [Gleason scores of] 9-10, who are most likely to experience mortality from [prostate cancer].

They go on to suggest that this result indicates an opportunity to augment current therapy by using anticoagulant therapy (at least in high-risk patients who are to be treated with radiation therapy).

The “New” Prostate Cancer InfoLink wants to emphasize that this paper is based on a very small number of patients, that many of the patients being treated by Jacobs et al. were probably elderly, required specific types of antcoagulant therapy for disorders utterly unrelated to their prostate cancer, and may therefore have had one or more serious co-morbid conditions, etc. In other words, we should be very cautious about over-interpreting the data from this type of retrospective analysis. However, …

It is far from unreasonable to consider the idea that concomitant anticoagulant therapy might be able to improve the survival of men with high-risk (or even intermediate-risk) prostate cancer when used along with standard forms of first-line therapy. Aspirin-based anticoagulant therapy is cheap and easily administered. However, it does come with risks, and so patients need to be carefully selected and regularly monitored to minimize risk for and identify quickly the well-known side effects of chronic aspirin therapy (gastrointestinal problems, including GI bleeding).

The question is now going to be whether this is of enough interest to stimulate a randomized Phase II trial to test this hypothesis prospectively. The “New” Prostate Cancer InfoLink would like to think that it is, but, in the current fiscal environment, even a small trial like this may be too hard to fund.

5 Responses

  1. ANY TABLE SHOWING DISEASE-SPECIFIC SURVIVAL FOR GS 9 & 10? (AND OTHER ODD OMISSIONS) This is getting curiouser and curiouser.

    I’m impressed by the numbers in this investigational research, especially those strikingly different rates for distant metastases and overall survival in the GS 9 and GS 10 group, but I’m curious why disease-specific survival for the GS 9 and 10 subset were not reported in the abstract, as they were for overall survival for that subset — especially in view of substantial mortality in that subset, mostly among the non-aspirin takers. I’m scratching my head wondering why that disease specific outcome was not reported.

    It seems possible, despite the strength in the correlations, that taking aspirin is a proxy for many in the aspirin taking group for more awareness about general health, better general medical care, or both. Using myself as an example, I have been taking an 81 mg aspirin daily for years, mainly in support of cardiovascular health, based on my doctor’s advice, which is backed by research and well publicized. These days, while not taking aspirin is an informed and thoughtful choice for many, I suspect that for many others it simply reflects ignorance of current good medical practice, and ignorance makes people vulnerable to a number of serious health threats, particularly heart attack and stroke.

    Here in advance is how I think disease-specific results would strike me. If disease-specific survival were about as superior for the aspirin takers as the results reported in the abstract, I would be encouraged that aspirin was having an effect on the cancer. On the other hand, if there were not much of a difference, I would suspect that not taking aspirin was associated with lower overall survival because it was neither enhancing cardiovascular health nor helping with other health concerns. Does that make sense?

    If I were evaluating a proposal for follow-up research, I would want to know the story about disease-specific survival before recommending funding.

    Meanwhile, I’ll keep popping that 81 mg aspirin.

    PS: I’m also curious why OS was so low at 37% among non-aspirin-taking GS 9 and 10 patients who were treated with presumably modern radiation (years 2005-2008) at a university, presumably with adequate monitoring, appropriate follow-up with androgen deprivation therapy (ADT), and employment of chemo. That 88% OS figure for the aspirin-takers with high-risk prostate cancer at 5 years looks reasonable, but not the 37% for the non-aspirin takers. What is going on here? Perhaps related, use of ADT was not reported. I would expect that all high-risk patients had adjuvant ADT, but that is not addressed in the abstract. Odd!

  2. Dear Jim:

    Since, like you, I have only seen the abstract, I am no wiser than you are. However, a lot could be explained by the ages and the co-morbidietis of these patients (which we also don’t know).

  3. The numbers in this abstract are truly remarkable, to the point at which Texas Southwestern probably ought to be incentivized to re-analyze additional details on these 74 high-risk patients. My guess, for what it is worth, is that the same subset who were using blood thinners were also getting regular (once a year) PSA tests. (This follows on Mr. Waldenfels’s insight that the thinner-users were also disproportionately the ones who were receiving close medical monitoring before being diagnosed with prostate cancer.) Thus their GS 9 and 10 lesions were relatively “recent” and had not metastasized yet. The non-users, not getting regular PSA readings, were much more likely to have metastatic extensions of various types by the time they were diagnosed.

    With luck, Texas Southwestern may be able to backtrack into enough of the medical records of these 74 patients -– maybe even ask some of them –- to determine whether the timing of PSA monitoring accounts statistically for some (maybe all) of the astonishing, and potentially very important, difference between the users and non-users of anticoagulants. (Touch wood, my 2010 GS9/IMRT/ADT/Hopkins treatment is working, so far. Maybe my daily 81 mg aspirin helps, too.)

  4. Dear Ken (and Jim):

    While I don’t want to “rain on anyone’s parade”, I do feel that there is a lot of speculation going on here based on things that might or might not be true. It is much too easy to start reading all sorts of things into this type of retrospective analysis. My own tendency is to simply take these data for what they are. Without some sort of prospective trial to evaluate the impact of anticoagulant therapy, we really haven’t got a clue what any of this means, and I will tell you very clearly that being on anticoagulant therapy is far from being any sort of indicator that a patient would get regular PSA tests; in some ways (especially in men > 70 years of age), it would be a very clear indicator not to be giving men PSA tests.

  5. I recall another paper whilst I was on my 2+ years of neoadjuvant hormone therapy, likely around 2009. Unfortunately I have lost the “bookmark” but will try to google it and find the research. It recommended a daily aspirin to thwart recurrence; I started that regimen — and continue it.

    In my mind it may have more to with controlling inflammation than anti-coagulation — just saying!

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