1. Carlson, Robert H.

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Regular aspirin use after diagnosis of prostate cancer is associated with a decreased risk of prostate cancer mortality and metastases, according to new data from the large observational Physicians' Health Study (1982-2009) reported at the 2016 Genitourinary Cancers Symposium (Abstract 306).

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With 27 years of follow-up on 22,071 male physicians enrolled in the study, 3,193 had been diagnosed with prostate cancer. Of those, 403 developed metastatic disease or died from prostate cancer, said Christopher Brian Allard, MD, Urologic Oncology Fellow at Brigham and Women's Hospital and Massachusetts General Hospital in Boston, Massachusetts, the study's first author.


"Among men with prostate cancer, regular aspirin use after diagnosis was associated with a 39 percent decreased risk of dying from prostate cancer," Allard said, presenting the findings in a presscast in advance of the Symposium.


But curiously, pre-diagnostic aspirin use did not confer a measurable benefit, he added with no apparent effect on the risk of being diagnosed with overall prostate cancer, high-grade prostate cancer, or locally advanced prostate cancer. Allard said previous studies have had mixed results regarding aspirin and prostate cancer prevention.


The Genitourinary Symposium is sponsored by the American Society for Radiation Oncology, American Society of Clinical Oncology, and the Society of Urologic Oncology.


The Physicians' Health Study evaluated the relationship between regular aspirin intake-defined as more than three tablets per week-and prostate cancer metastases or prostate cancer death. Secondary study outcomes were the incidence of Gleason 8-10 tumors, and T3b-T4, N1, or M1 cancers.


Study Details

At the press briefing, moderator and ASCO spokesperson Sumanta Pal, MD, Assistant Professor and Co-Director of Kidney Cancer Program at City of Hope, said to keep in mind that these findings are from an observational study.


"The findings are thought provoking, but perhaps this is best followed by formal clinical trials comparing use of aspirin to either no treatment or perhaps a placebo," he said. Pal also pointed out that the aspirin dosage may have varied widely among the men in the study, and that it is not known which prostate cancer patients would benefit from taking aspirin.


Allard agreed that it is premature to recommend aspirin for prevention of lethal prostate cancer. "But men with prostate cancer who may already benefit from aspirin's cardiovascular effects could have one more reason to consider regular aspirin use," he said.


Both Allard and Pal emphasized that men should discuss the potential benefits of aspirin with their doctors, in terms of both cardiovascular health and risk of prostate cancer death, and also consider potential risks of regular aspirin use.


Aspirin and Beta Carotene

The Physicians' Health Study was begun in 1982 to test the benefits and risks of aspirin and beta carotene in the primary prevention of cardiovascular disease and cancer. The study received funding from the Prostate Cancer Foundation and the National Institutes of Health/National Cancer Institute.


After the original randomized trial ended in 1995, researchers continued to follow study participants through annual questionnaires. At the initiation of this trial men were taking aspirin 325 mg every other day, but that was stopped after five years when cardiovascular benefits were seen. What doses men took on their own after that was not recorded.


Platelet Activity

Asked to speculate on the mechanism of action involved here, Allard said one hypothesis is that aspirin, by depleting platelets, allows the immune system to recognize the cancer.


"Animal studies demonstrate that depleting platelets from an animal with cancer prevents deposition of cancer in bone, and platelets probably shield circulating cancer cells from immune recognition," Allard said. "That would explain why aspirin has no apparent effect on local cancer but there is an effect on metastatic disease."


He said in meta-analyses in the literature, the overall weight of evidence suggests that aspirin may prevent advanced prostate cancer.


"We did not find that, but then previous studies have often defined advanced cancer as the composite of advanced local disease and advanced metastatic disease.


"We separated that out and focused only on metastatic or lethal prostate cancer, and we do see a clear benefit but without seeing any benefit from overall or advanced local prostate cancer."