In the News focuses on media reports that your patients may have questions about at their next visit. This continuing column will provide summaries of articles in the popular press that may prompt such questions, as well as comments from colleagues in the field.

Over the past few weeks, Stanley L. Liauw, MD, Associate Professor, Department of Radiation and Cellular Oncology at the University of Chicago, has received a lot of emails from men with prostate cancer “who are wondering whether they should take aspirin,” Dr. Liauw said. These men are contacting Dr. Liauw because he is the corresponding author of a study finding a “very strong association” between use of aspirin and reduced risk of death due to prostate cancer. The study was published in the Journal of Clinical Oncology (JCO).¹

Risk-Benefit Considerations

“The study did find a very strong association in aspirin users having a reduced chance of prostate cancer failure, but the type of the analysis done probably isn’t strong enough to make a recommendation formally for men with prostate cancer to start taking aspirin,” Dr. Liauw said in an interview with The ASCO Post. “What we found was as association in looking at a large registry of men in a database, but this doesn’t really speak to the balance of the risks and benefits and it also doesn’t imply causality,” he continued. “We really need a trial to answer whether the benefits outweigh the risks.” Those risks include hemorrhagic stroke and gastrointestinal bleed. (For more information on risks, see sidebar, “Expect Questions from Your Patients.”)

The Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database was used to investigate whether anticoagulant therapy was associated with prostate cancer–specific mortality among men with localized adenocarcinoma of the prostate treated with radical prostatectomy or radiotherapy (brachytherapy, external-beam radiation, or a combination of the two). Among 5,955 men meeting these criteria, 2,175 (37%) were receiving anticoagulants (warfarin, clopidogrel [Plavix], enoxaparin, and/or aspirin).

“After a median follow-up of 70 months, risk of prostate cancer–specific mortality was significantly lower in the anticoagulant group compared with the non-anticoagulant group (3% vs 8% at 10 years, P < .01),” according to the study report. “Analysis by type of anticoagulant medication suggested that the prostate cancer–specific mortality reduction was primarily associated with aspirin,” the authors added. “In multivariable analysis, use of aspirin was significantly associated with improved prostate cancer–specific mortality, independently of other prognostic factors.”

Subgroup Findings

A subgroup analysis by clinical risk category found “the reduction in prostate cancer–specific mortality was most prominent among patients with high-risk disease who have the highest risk of developing metastases.” In this subgroup, the 10-year prostate cancer–specific mortality was 4% for men taking anticoagulants vs 19% for those not taking anticoagulants (P < .01). High-risk disease was defined using National Comprehensive Cancer Network (NCCN) guidelines. “That means men who had clinical T3 disease, or Gleason 8 to 10 cancers cancers, or a prostate-specific antigen level of 20 ng/mL or higher,” Dr. Liauw explained.

“Men with intermediate-risk disease had a modest difference in prostate cancer–specific mortality with anticoagulant use (3% vs 6%, P = .01). The difference was not statistically significant in low-risk patients (10-year prostate cancer–specific mortality of 2% vs 4%, P = .12),” the authors reported.

Men who took anticoagulants also had a significantly lower risk of disease recurrence and bone metastases. The benefit from anticoagulants extended to patients in both the radical prostatectomy and radiotherapy groups.

Conflicting Results

“Our findings corroborate and strengthen the hypothesis that aspirin may have chemopreventive and antineoplastic effects,” the authors concluded. They also acknowledged, however, that findings from other studies of aspirin and other anticoagulants have been conflicting and inconclusive, possibly due to the heterogeneity in cancer types and stages.

Another study released early online by JCO at the same time as the aspirin and prostate cancer study “suggests that use of aspirin, other NSAIDs, and acetaminophen is not importantly associated with the risk of postmenopausal breast cancer, either overall or by specific subtype.”² A recently published analysis of daily aspirin use and overall cancer mortality among 100,139 men and women with no history of cancer in the Cancer Prevention Study II Nutrition Cohort found that current daily aspirin use “was associated with modestly lower overall cancer mortality.³ 

Dose and Duration Not Addressed

The prostate cancer study did not address in detail the dosage, duration, and timing of aspirin or other anticoagulants. Patients reported their use of medications at study entry and at approximately 1-year intervals and were classified as “ever users” or “never users.” Users likely included those who took adult doses of aspirin occasionally or frequently for pain reduction as well as those who took smaller doses for primary prevention of cardiovascular disease.

“So it is probably a heterogeneous group,” Dr. Liauw said. “Despite the fact that people may have taken aspirin ever single day or more sporadically after they were treated for prostate cancer, it is interesting to note that there was still a strong association with prostate cancer mortality,” he commented.

“The optimal usage of aspirin as well as the potential toxicity should be addressed in a prospective study,” the authors noted in their report. “We are exploring the feasibility of doing such a trial,” Dr. Liauw said. “It will take a lot of work and patience. There are many details to be ironed out, and there are challenges to doing a randomized study. For example, in this group you can see that a lot of men were already on aspirin. We would only be able to recruit patients who are not on aspirin. Then we would probably have to double-blind the study and apply a placebo, and that might impose challenges on men who want to go on aspirin later for cardiovascular reasons. I think it could probably be worked out, but the discussion is very preliminary right now.”

Looking for the ‘Next Big Sensitizer’

Dr. Liauw explained that the recently reported study was conducted “as an offshoot” of a study to determine the risk of bleeding in patients who received radiation treatment for prostate cancer. “One of the issues with radiation for prostate cancer is that it can damage the bladder and rectal tissue around the prostate. We try to use planning parameters to spare those tissues, but in people who are on anticoagulants, the risks of bleeding are higher,” Dr. Liauw noted.

“Therefore, we initially conducted a study to try to quantify the elevated risk of bleeding,” he continued. “Once we had those data collected, we decided to look at the disease outcomes because of the evidence suggesting that anticoagulants may have an anticancer effect. In doing that, we found an association. We were pretty surprised at the magnitude of the benefit, which is similar to what is shown in this paper.”

Following the initial study with anticoagulants, Kevin S. Choe, MD, of The University of Texas Southwestern Medical Center in Dallas and the lead author of the current study, expanded the analysis, using the CaPSURE database to include a larger number of men, and not only men treated with radiation, but also men treated with surgery. “In doing the analysis with the CaPSURE database, we tried to separate out the nonaspirin anticoagulants and then compared them to the aspirin anticoagulants. It seemed then that the benefit came from aspirin use rather than from warfarin and clopidogrel and other anticoagulants,” Dr. Liauw said.

“When we did the analysis as a radiation-only group, we didn’t know whether this effect was related to radiation sensitization or something else. As radiation oncologists, we are always interested in finding the next big sensitizer,” Dr. Liauw said. “If it were the case that this was a sensitizer, we might have seen an effect in the radiation group, but not in the surgery group. Our findings suggest that there is another mechanism of action, or at least it is a sensitizer plus it has other effects.” ■

Disclosure: Dr. Liauw reported no potential conflicts of interest.

References

1. Choe KS, Cowan JE, Chan JM, et al: Aspirin use and the risk of prostate cancer mortality in men treated with prostatectomy or radiotherapy. J Clin Oncol. August 27, 2012 (early release online).

2. Zhang X, Smith-Warner SA, Collins LC, et al: Use of aspirin, other nonsteroidal anti-inflammatory drugs, and acetaminophen and postmenopausal breast cancer incidence. J Clin Oncol. August 27, 2012 (early release online).

3. Jacobs EJ, Newton CC, Gapstur SM, et al: Daily aspirin use and cancer mortality in a large US cohort. J Natl Cancer Inst 104:1208-1217, 2012.