Endocrine Therapy for Prostate Cancer May Hike Cardiovascular Disease Risk

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BERLIN—Prostate cancer patients treated with endocrine approaches have an increased risk for cardiovascular disease (CVD), according to findings of a Swedish study presented here at a joint conference of the European Cancer Organization and European Society for Medical Oncology.

Lead author Mieke Van Hemelrijck, MSc, a cancer epidemiologist at King's College London, UK, called this the first large study to address the cardiovascular adverse effects of endocrine treatment in prostate cancer, which included orchiectomy, gonadotropin-releasing hormone (GnRH) agonists, or anti-androgen (AA) monotherapy.

“We saw an increased risk for the development of, and death from, each type of cardiovascular disease,” Van Hemelrijck reported. “While all forms of endocrine therapy were associated with risk, the least risk was seen with anti-androgen monotherapy. This may be because these agents do not block the production of testosterone, but only its access to the prostate, so some testosterone is still circulating and providing a cardioprotective effect.”

The cohort was drawn from PCBaSe Sweden—a register-based resource for prostate cancer research. PCBaSe is based on the National Prostate Cancer Registry, which covers more than 96% of all incident prostate cancers compared to the Swedish Cancer Registry. Between 1997 and 2006, PCBaSe registered more than 80,000 prostate cancer patients. Investigators looked for concomitant diagnoses of myocardial infarction (MI), arrhythmia, ischemic heart disease (IHD), and heart failure (HF).

Primary endocrine treatment was delivered to 30,642 prostate cancer patients, with 38% receiving short-term AA plus GnRH agonists, 30% GnRH agonists alone, 17% orchiectomy, and 11% AA alone. For all cardiovascular diagnoses, incidence was increased in persons receiving endocrine treatment, Van Hemelrijck said. 

Compared with expected rates, the researchers observed 24% more MI cases and 28% more MI-related deaths, 19% more arrhythmias and 5% more arrhythmia-related deaths, 31% more IHD and 21% more IHD-related deaths, and 26% more HF and 26% more HF-related deaths.

 “A causal effect was not shown,” she concluded, “but we believe heart disease needs to be taken into account before starting prostate cancer patients on endocrine treatment, especially considering we are now using this approach not only for metastatic disease but for less advanced disease as well.”

At a press briefing, co-scientific chair of ESMO-ECCO 2009, Fortunato Ciardiello, MD, Professor of Medical Oncology at Second University of Naples, Italy, said the size of the database suggests these findings “are certainly clinically relevant.”

“We need to take into account, in treating prostate cancer patients—especially with adjuvant treatment—that testosterone deprivation has more impact on the patient's life than its direct effect on the androgen receptor. In our choice of treatment, we should balance these factors. These findings could change our attitudes toward prostate cancer treatment.”

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