Aspirin Does Not Reduce Mortality in Prostate Cancer

Megan Brooks

April 14, 2015

The use of aspirin after newly diagnosed nonmetastatic prostate cancer does not lower disease-specific or overall mortality, according to a large population-based study conducted in the United Kingdom.

In fact, the risk for prostate cancer mortality increased in men who started aspirin therapy after diagnosis.

"It is likely that the observed risk is due to some confounding factors," said Laurent Azoulay, PhD, from the Department of Oncology at McGill University in Montreal.

"It is possible that men who start aspirin after their prostate cancer diagnosis have other conditions that are associated with worse survival. As such, our results should not detract men from starting aspirin after their diagnosis," Dr Azoulay told Medscape Medical News.

Several observational studies have assessed the association between aspirin use and prostate cancer outcomes, with mixed results. These studies, Dr Azoulay said, had "important methodologic limitations that exaggerated the potential effects of aspirin in men with prostate cancer. Using the appropriate methods, we found that aspirin was not associated with a protective effect. This does cast some doubt on the potential antitumor effects of this drug in this population," he explained.

The study was published in the April issue of the Journal of Urology.

Using the National Cancer Data Repository, the Clinical Practice Research Datalink, and other databases, the researchers identified 11,779 men with nonmetastatic prostate cancer diagnosed from 1998 to 2009. The mean age at diagnosis was 71.3 years.

During a mean follow-up of 5.4 years, 1793 men died of prostate cancer and 3502 died from any cause.

Overall, the use of aspirin after diagnosis was associated with a 46% increased risk for prostate cancer mortality (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.29  - 1.65) and a 37% increased risk for all-cause mortality (HR, 1.37; 95% CI, 1.26 - 1.50). There was no evidence of a duration-response relation between aspirin use and prostate or all-cause mortality.

However, the increased risks for prostate cancer mortality (HR, 1.84: 95% CI, 1.59 - 2.12) and all-cause mortality (HR, 1.70; 95% CI, 1.53 - 1.88) were restricted to patients who initiated aspirin after diagnosis. No increased risk was observed in patients who started aspirin before diagnosis, a finding consistent with three other observational studies, the researchers note.

In light of a recent study that reported decreased prostate cancer mortality in high-risk patients (HR, 0.60; 95% CI, 0.37 - 0.99) (J Clin Oncol. 2014;32:3716-3722), Dr Azoulay's team performed a similar analysis but were unable to replicate the finding (HR, 1.85; 95% CI, 1.51 - 2.30).

"Taken together, these results argue against a protective association between the use of aspirin and the risk of prostate cancer mortality and all-cause mortality," the researchers say.

More Study Needed

"It's not current practice to prescribe aspirin for the sole purpose of preventing death in men with prostate cancer," Dr Azoulay noted. "These drugs are commonly used in patients with cardiovascular conditions, where benefits have been observed. Our null results should not change this practice."

"It's possible that the use of aspirin after prostate cancer diagnosis is related to prostate cancer disease progression," the researchers explain. They note that certain prostate cancer treatments, such as androgen-deprivation therapy, are associated with an increased risk for cardiovascular events and, "thus, it is possible that the prescribing of aspirin was the result of treatment-related adverse events, which themselves are associated with worse disease progression."

Although the researchers adjusted for more than 30 potential confounders, residual confounding remains a possibility, they point out.

There are "several shortcomings" in this study, said Kevin Choe, MD, PhD, radiation oncologist at University of Texas Southwestern Medical School in Dallas, who has studied aspirin use in prostate cancer but was not involved in this study.

"For example, there are clinical factors known to be most powerful prognostic factors in prostate cancer outcomes, including Gleason grade and PSA value," he told Medscape Medical News. "In this registry study, they were missing these critical values in more than 50% of their patients, and therefore they were not accounted for in their analysis."

The researchers acknowledge these limitations and others, including the relatively short follow-up period (5.4 years) and the mean advanced aged of the men at study entry (71.3 years).

"Additional well-conducted studies are needed," said Dr Azoulay, to "shed more light on the effects of aspirin in men with prostate cancer."

J Urol. 2015;193:1220-1225. Full text

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