Hormone Therapy for Prostate Cancer Linked to Heart Risks

TUESDAY Oct. 9, 2007 -- Prostate cancer patients receiving androgen-deprivation therapy, a common form of hormone treatment proven to slow tumor growth and prolong life, may face a nearly threefold higher risk of dying from heart disease, a new study suggests.

The apparent danger results from a drop in testosterone levels that is central to androgen-deprivation therapy's (ADT) effectiveness at curbing prostate cancer, the study authors said.

This drop in testosterone can provoke insulin resistance, leading to type 2 diabetes, as well as a gain in body mass, body fat and so-called bad cholesterol. Collectively, this group of problems is called the "metabolic syndrome," a condition long-associated with cardiac complications.

"However, I think overall ADT does help people with prostate cancer, and until it's studied further this can't be considered proof that there's a connection between the cardiac effects and hormone therapy," said study author Dr. Henry K. Tsai, who throughout the study period served as a resident in training in the Harvard Radiation Oncology Program in Boston.

"But patients need to think about being evaluated carefully by their doctor to see whether they're appropriate candidates for hormone therapy and be informed about the potential risks," Tsai added.

This new finding, published in the Oct. 17 issue of the Journal of the National Cancer Institute, follows research released in 2005 that highlighted ADT's link to an increased risk for bone fractures and osteoporosis.

The new findings are based on an analysis of medical records and questionnaires completed by nearly 4,900 patients between the ages of 39 and 86 who had been diagnosed with localized prostate cancer between 1995 and 2004.

All the patients had participated in a larger nationwide prostate cancer research project involving more than 13,000 men, during which all had indicated whether they had any preexisting medical complications in addition to cancer.

Of the 4,900 patients, nearly 3,300 had undergone prostate removal surgery following diagnosis.

The remainder underwent nonsurgical treatments, such as external beam radiation therapy; brachytherapy (involving the insertion of small radioactive pellets directly into the prostate); and/or cryotherapy (involving the freezing of tumor cells).

In addition, 266 of those patients who underwent surgery and 749 of those receiving an alternate treatment also received androgen-deprivation therapy.

The patients were tracked for an average of about four years following the start of all treatments; the patients receiving ADT did so for an average of about four months.

Tsai and his colleagues found that patients over the age of 65 who had undergone both prostate removal surgery and ADT had a 5.5 percent increased risk of dying from a cardiac event within five years of starting the hormone treatment. This compared to a 2 percent greater risk among patients older than 65 who had surgery alone.

The "relative risk" jump was similar among younger patients. Those under 65 who had surgery and hormone therapy had a 3.6 percent greater risk of death from heart disease within five years, compared with a 1.2 percent risk among those undergoing surgery alone.

ADT was not associated with any increased cardiac risk among patients undergoing any of the nonsurgical treatments.

An editorial accompanying the study calls for more research into the topic.

Jerome Seidenfeld and his colleagues at the University of Connecticut Health Center suggest that while Tsai's analysis of previously collected data raises an "interesting hypothesis," no definitive link to cancer risk can be proved until a clinical trial of prostate cancer patients currently undergoing hormone treatment is launched.

Tsai agreed.

"I pretty much feel similarly," Tsai said. "The editorial emphasizes that this is a preliminary study, and clinical trials are the gold standard. And we need one to confirm our findings."

Tsai, currently working as a radiation oncologist with Radiation Oncology Consultants in Princeton, N.J., said he doesn't want prostate cancer patients to view androgen-deprivation therapy with alarm.

"I don't think patients should be afraid," he said. "This is just what I'd call emerging data, and while the relative increase in risk for heart disease is large, in absolute terms the risk is still very small."

Dr. Nelson Neal Stone, a clinical professor of urology and radiation oncology at Mount Sinai School of Medicine in New York City, said the exact mechanism by which ADT might boost the risk for cardiac complications remains undefined, despite a widespread appreciation for the array of problems that accompany the metabolic syndrome.

In that light, he suggested that physicians should target the onset of the life-threatening syndrome as well as the life-prolonging treatment.

"The message is that we need to start paying attention to our patients' general health when we put them on hormonal therapy," he said. "And perhaps we should be putting them on a diet to control for the potential side effects of the therapy, and the serious impact it can have on their health."

"We can't take away the hormones altogether because there's a major benefit to that treatment," Stone added. "But we need to develop a good strategy for dealing with the negative consequences that occur."

More information

To learn more about prostate cancer and its treatment, visit the American Cancer Society.

Posted: October 2007


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