Aspirin Reduces Risk of Mortality for Men with High-Risk Prostate Cancer

A few years ago I posted a blog on two published studies connecting the humble anti-inflammatory drug aspirin with less likelihood of prostate cancer (PCa) recurrence among high-risk patients. The two studies I cited were both published seven years ago. Zaorsky, et al.[i] based their analysis on 2051 cases, while Choe, et al.[ii] had access to 5955 records. The evidence of reduced PCa-specific mortality (PCSM) among high-risk patients who took daily aspirin was clear in both. However, both articles noted that the exact mechanism by which aspirin may prevent the formation, progression, and metastasis of certain types of cancer cells was not fully understood. Theory pointed to an anti-coagulation effect, but other anti-coagulant drugs besides aspirin did not seem to operate that way on cancer. That was back in 2012.

A 2014 study draws on a larger data pool

Two years later, Jacobs, et al.[iii] published their investigation, based on more dramatic numbers, in which they compared PCSM risk among patients who used daily aspirin before being diagnosed (8,427 cases) and those who used aspirin after diagnosis (7118 cases). They included patient age at diagnosis, Gleason score, tumor stage, primary treatment method, etc. Thus, they created a stratified matrix from which to discern if any pattern showed that linked aspirin use and reduced PCSM, in any given subset of the total pool of patients—in itself a remarkable statistical achievement.

Before I share their results, it’s important to note why the PCa patients in these studies were taking aspirin to begin with. The reason goes back to the anti-coagulation properties of aspirin: it’s a blood thinner. It was used as a precaution against cardiovascular disease and stroke, not because of prostate cancer. Serendipity sometimes occurs in medicine. A procedure or drug administered for one therapeutic purpose proves to benefit recipients in an unexpected way. For example, the diabetes drug metformin turns out to have preventive properties for many disease states, and may even have anti-aging properties! Thus, the observation that aspirin seems to lower the risk of death from prostate cancer is one of those serendipitous events.

Results of the Jacobs study

The Jacobs study found that across their entire pool of cases on average, neither pre-diagnosis aspirin use nor post-diagnosis aspirin use was associated with more favorable PCSM (as compared with non-aspirin users). However, one subset of patients did indeed have a significantly lower mortality rate: men diagnosed with high-risk PCa who also used daily aspirin after diagnosis. While some studies don’t support this finding, it’s the same result demonstrated by the two 2012 published studies and others. The Jacobs study was “…the largest study to date of aspirin use and PCSM among men diagnosed with nonmetastatic prostate cancer,” [iv] so its results must be considered as strong evidence of this effect.

Why would aspirin help in high-risk cases?

In the article’s introduction, the authors speculate that the anticoagulative property of aspirin, due to its inhibition of platelet activation, discourages cancer cell activities that rely on hijacking platelets and the molecular factors they contain. They also write that its apparently selective effect on high-risk prostate cancers might result from molecular characteristics of cancers that progress more rapidly—and are thus diagnosed at a higher grade or more advanced stage—and possibly have certain susceptibility to inhibition by aspirin. However, they write, “We are not aware…of specific biologic evidence to support this possibility.” The mystery, therefore, continued.

Now, in 2019, two Finnish authors summarize a current hypothesis of aspirin’s effect:

It is a noncompetitive inhibitor of cyclooxygenase enzyme 1 (COX-1) and also modifies the action of COX-2, an enzyme thought to be important in prostate cancer progression. This activity has anti-inflammatory effects that might be beneficial, because chronic intraprostatic inflammation has been associated with increased risk for high-grade prostate cancer. In addition, several COX-independent anticancer mechanisms of aspirin action have been described. Aspirin also inhibits the function of platelets, which are thought to assist in cancer dissemination. In vitro, aspirin effectively inhibits prostate cancer cell growth.[5]

Readers will forgive me for not explaining the COX enzymes. Suffice it to say that biologists and other researchers may be closing in on the precise nature of aspirin’s effect on cancer cells in a way that is beneficial to patients. Such an inexpensive and widely available anti-inflammatory would be a definite boon for cancer patients if we can figure out how to harness its anti-cancer potential.

Meanwhile, all the authors I’ve mentioned call for larger randomized studies to determine if, in fact, the evidence truly supports daily aspirin use as a PCa deterrent. While it’s important to understand HOW it works, it’s crucial to confirm THAT it works before raising universal hope.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

[i] Zaorsky NG1, Buyyounouski MK, Li T, Horwitz EM. Aspirin and statin nonuse associated with early biochemical failure after prostate radiation therapy. Int J Radiat Oncol Biol Phys. 2012 Sep 1;84(1):e13-7.
[ii] Choe KS, Cowan JE, Chan JM, Carroll PR et al. Aspirin use and the risk of prostate cancer mortality in men treated with prostatectomy or radiotherapy. J Clin Oncol. 2012 Oct 1;30(28):3540-4.
[iii] Jacobs EJ, Newton CC, Stevens VL, Campbell PT et al. Daily aspirin use and prostate cancer-specific mortality in a large cohort of men with nonmetastatic prostate cancer. J Clin Oncol. 2014 Nov 20;32(33):3716-22.
[iv] Ibid.
[v] Murtola TJ, Veitonmäki T. Aspirin and Prostate Cancer Mortality: The Role of Tumor Grading Misclassification? April 2, 2019. https://annals.org/aim/article-abstract/2727207/aspirin-prostate-cancer-mortality-role-tumor-grading-misclassification

 

About Dr. Dan Sperling

Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Prostate Center.

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