Reference
Choe KS, Cowan JE, Chan JM, Carroll PR, D'Amico AV, Liauw SL. Aspirin use and the risk of prostate cancer mortality in men treated with prostatectomy or radiotherapy. J Clin Oncol. 2012 Oct 1;30(28):3540-3504.
Design
This study analyzed the associations between anticoagulant use and cancer outcome in men previously treated for prostate cancer.
Participants
Study participants are enrolled in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) Study, a longitudinal, observational registry of men with biopsy-proven prostate cancer. Patients from 41 institutions nationwide have been enrolled in this study since 1995. Data from 5,955 men with localized adenocarcinoma of the prostate, who were treated with either radiation therapy or radical prostatectomy, were analyzed in this study. Median age was 64 years. The percentages of patients with low, intermediate, and high-risk disease were 42%, 36%, and 22% respectively. After a median follow-up time of 70 months, 779 patients had died and of these 193 (25%) had died of prostate cancer.
Study Medication and Dosage
Of all the men studied, 2,175 (37%) had taken anticoagulant therapy. And of these, the majority (84%) had taken aspirin and about a fifth (21%) warfarin. Smaller percentages of participants had taken clopidogrel, enoxaparin, or a combination of 1 or more of these anticoagulants.
Outcome Measures
The risk of prostate cancer-specific mortality (PCSM) was compared between those men on anticoagulant therapy and those not.
Key Findings
Men taking anticoagulants had a significantly lower risk of dying from prostate cancer. At 7 years only 1% of those taking anticoagulants had died compared to 3% of those not taking anticoagulants. At 10 years these number had grown to 3% and 8%. Those taking anticoagulants also had significantly lower risk of disease recurrence and bone metastasis.
The impact of anticoagulant use was more pronounced in those with high-risk disease. In this subgroup, PCSM was 4% for those taking anticoagulants compared to 19% for those not.
Convincing a man who has been diagnosed and treated for high-risk prostate cancer to take aspirin may increase his chance of surviving for 10 years by a factor of nearly 5.
The data was further analyzed in a Cox proportional hazards regression model comparing aspirin use, other anticoagulant use, initial prostate-specific antigen (PSA), treatment modality, and Gleason score. This confirmed that aspirin use was independently associated with lower PCSM (HR: 0.43; 95% CI: 0.21–0.87). Use of other non-aspirin anticoagulants was not significantly associated with PCSM.
Practice Implications
Convincing a man who has been diagnosed and treated for high-risk prostate cancer to take aspirin may increase his chance of surviving for 10 years by a factor of nearly 5. For the average man who has had prostate cancer, taking aspirin will reduce his risk of dying from the cancer by 57%.
That aspirin might exert anticancer action isn’t a new idea; Kune et al first noticed a protective effect in Melbourne back in the late 1970s.1 Their observations triggered a wave of animal studies and observational and clinical trials that now suggest aspirin protects against a range of cancers, but especially colon cancer.
There is still no consensus as to why or how aspirin affects cancer. It had been thought the effect resulted from aspirin's blocking COX-2 activity. Blocking COX-2 would block the inflammation that aids tissue recovery from injury, which also appears to aid and encourage tumor cell growth. A second hypothesis suggests that aspirin blocks production of NF-kappaB. Both explanations suffer a similar weakness. The doses of aspirin now shown to protect from cancer are so low that they are not adequate to impact either COX-2 or NF-kappaB.
A third possible explanation, favored in the current paper, is that aspirin affects platelets. Even low-dose aspirin impairs platelet activity. In metastasis, as cancer cells spread through the blood, they are typically surrounded by platelets, which may somehow aid them in colonizing new sites for growth. Aspirin may act through decreasing and impairing these platelets. This argument is supported by the lack of anticancer action seen with the other anticoagulants tracked in this study that do not impede platelet activity.
It is not a lack of understanding the mechanism of action that hinders aspirin use by my colleagues and our patients. It is more a matter of principle. In the practice of naturopathic medicine and other alternative and complementary practices, it often seems that we have drawn an invisible line between ‘acceptable’ natural therapies and ‘unacceptable’ drug therapies. Aspirin is often viewed as on the wrong side of this line, something that we, and our patients, may be reluctant to use. The perception is that it is simply not natural enough. As risk of injury from using low dose aspirin has been reported to be minimal, it is unlikely that objections are due to any dangers from its use.
Given the apparent magnitude of the benefits demonstrated in this study, it may be time to consider suggesting regular aspirin to a wider population of patients—in this instance, men who have been treated for prostate cancer.
Note: Aspirin use increases risk of bleeding, as it is an anticoagulant. It also increases risk of stomach ulcers in a dose-dependant manner. Individuals should consult their healthcare providers prior to beginning use of daily aspirin.
The Natural Medicine Journal has reviewed two previous aspirin studies:
- Daily Aspirin may reduce risk of cancer death January 2011
- Aspirin to reduce breast cancer recurrence December 2011
For more research involving integrative oncology, click here.
