Prostate Cancer Treatment Can Be Risky

Hormone Treatment May Have Adverse Effects for Some Patients

From the WebMD Archives

Feb. 18, 2008 (San Francisco) -- For some men with prostate cancer, the risks of a common treatment may outweigh the benefits, new research suggests.

At issue is androgen deprivation therapy to lower levels of male hormones that can fuel prostate cancer growth. Alternately called hormone treatment or ADT, it's a well-accepted treatment for men with advanced cancer that has spread outside the prostate. ADT can be done by orchiectomy (removal of the testicles) or hormone therapy alone to reduce the production of male hormones; it also may be done in combination with anti-androgens, which block the effect of male hormones.

Androgen deprivation therapy -- often in combination with radiation -- is also a standard of care for men with early cancer that is still confined to the prostate.

But it may not always be the best choice, suggest several new studies presented at the 2008 Genitourinary Cancers Symposium.

One study shows that a one-two punch of radiation plus ADT may actually be harmful for older men with early prostate cancer who suffer from other health problems.

Another study of men with early prostate cancer suggests that compared with those who chose watchful waiting -- close monitoring for signs of tumor growth -- hormone therapy may raise the risk of dying.

Dutch researchers report that for some men, delaying androgen deprivation therapy until they start to get worse -- rather than starting it right after diagnosis -- will not cut the odds of survival. But it may improve their quality of life, they say.

Not all the news about ADT was alarming.

In contrast to previous research, Harvard doctors found no evidence that hormone therapy raises the risk of dying of heart disease.

"Androgen deprivation has a high cure rate for more aggressive tumors," says Eric A. Klein, MD, head of urologic oncology at the Cleveland Clinic. Klein, a spokesman for the American Society of Clinical Oncology, was not involved with the research.

"What hasn't been appreciated is that even short-course hormone therapy can have adverse health consequences. We need to be more judicious about the use of hormone treatment (ADT) in our patients," Klein tells WebMD.

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ADT and Men With Chronic Health Conditions

Anthony D'Amico, MD, PhD, of Harvard Medical School, and colleagues followed more than 200 men with localized prostate cancer who were treated with radiation alone or radiation plus ADT therapy for six months.

All had at least one risk factor for prostate cancer disease progression.

By eight years later, men who got radiation alone were 80% more likely to die than if they received hormone treatment plus radiation.

But further analysis showed that the survival benefit associated with hormone treatment was "pretty much confined to men who were otherwise healthy," D'Amico tells WebMD. Men with other illnesses were twice as likely to die if they received androgen deprivation therapy, D'Amico says.

The bottom line, says Klein, is that older men with other health ills who have a high risk of dying of causes other than cancer can probably be treated with radiation alone.

"They may actually be harmed by ADT, even though it has a higher cure rate overall. It's a matter of what gets you first," he says.

ADT vs. Watchful Waiting

In a second study, Philadelphia researchers found men who opted for "watchful waiting" lived longer than men who got hormone treatment.

Yu-Ning Wong, MD, and colleagues at Fox Chase Cancer Center analyzed data on more than 22,000 men ages 65 to 80 in a National Cancer Institute database who were diagnosed with localized prostate cancer between 1991 and 1999. About one-fourth underwent hormone therapy. The others opted for "watchful waiting." None of them got either surgery or radiation treatment.

By the end of 2002, men who got ADT were 17% more likely to die than those who opted for close observation.

"It's possible that the men who received ADT got the treatment because of rising PSA levels, indicating worse disease," Wong says.

"But it's also possible that hormone therapy, which has been associated with heart disease, osteoporosis, and other health problems, could have compromised survival," Wong tells WebMD.

Delaying ADT

In another study, Dutch researchers showed that men who delayed hormone therapy were no more likely to die than those who started treatment immediately.

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They studied 234 men with prostate cancer that had spread to lymph nodes, but not to other organs. None of the men were given radiation. Instead, they were assigned to immediately start treatment with a hormonal drug called Zoladex or to get Zoladex only when they got worse. Zoladex works to interfere with the production of male hormones.

By 13 years later, men in both groups were equally likely to be alive.

Researcher Fritz H. Schroder, MD, PhD, of Erasmus Medical Center in Rotterdam, Netherlands, says delayed therapy offered men a better quality of life for an average of 18 months.

Bruce J. Roth, MD, head of the committee that chose the studies to be presented at the meeting and a medical oncologist at Vanderbilt-Ingram Cancer Center in Nashville, Tenn., says further study is needed.

But given the findings, he says he might hold off on ADT in men who aren't committed to the idea of earlier treatment.

ADT and Heart Risk

Harvard researchers found no evidence that men treated with radiation plus ADT were more likely to die of heart disease than patients treated with radiation alone.

Jason Efstathiou, MD, and colleagues studied about 950 men with advanced prostate cancer. That means the cancer has grown through the outer rim of the prostate and into nearby tissue.

They were given either radiation plus hormone therapy with Zoladex, or radiation alone.

Over a five-year period, 4.1% of men given Zoladex died of heart disease vs. 6.5% of men given radiation alone -- a difference so small it could have been due to chance.

However, men on hormone treatment were more likely to die of any cause, Efstathiou says. "The absence of an apparent increase in death due to heart disease does not exclude the possibility that hormone therapy increases the risk of noncancer death due to other mechanisms."

According to Klein, "All these studies are telling us the same thing. Hormone therapy carries risks and we should only use it in those patients most likely to benefit."

Men should talk to their doctors about the risk and benefits of ADT, he advises.

D'Amico adds that men who have risk factors for heart disease, such as smokers and people with diabetes, should undergo a cardiac evaluation before they start hormonal therapy to treat prostate cancer.

WebMD Health News Reviewed by Brunilda Nazario, MD on February 18, 2008

Sources

SOURCES:

Genitourinary Cancers Symposium, San Francisco, Feb. 14-16, 2008.

Eric A. Klein, MD, head, section of urologic oncology, Cleveland Clinic.

Anthony D'Amico, MD, PhD, department of radiation oncology, Harvard Medical School.

Yu-Ning Wong, MD, Fox Chase Cancer Center, Philadelphia.

Fritz H. Schroder, MD, PhD, Erasmus Medical Center, Rotterdam, Netherlands.

Bruce J. Roth, MD, head, Genitourinary Cancers Symposium program committee; Vanderbilt-Ingram Cancer Center, Nashville, Tenn.

Jason Efstathiou, MD, Harvard Medical School.

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