Androgen deprivation therapy does not keep localized prostate cancer from spreading, new study says

Hormonal treatment gaining popularity for localized prostate cancer despite little understanding of its effectiveness

SAN FRANCISCO -- Oregon Health & Science University Cancer Institute researchers wanted to know if depriving men of testosterone actually keeps cancer from spreading beyond the prostate. What they found is that men who have localized prostate cancer with certain high-risk features and receive this treatment -- known as androgen deprivation therapy -- remain at risk of dying from prostate cancer.

"The notion that androgen deprivation therapy will hold prostate cancer at bay while you die of something else is not proving to be entirely true," said Tomasz Beer, M.D., director of the Prostate Cancer Research Program in the Oregon Health & Science University Cancer Institute.

This is especially important because recent studies of physician practice trends show that androgen deprivation therapy is being used with increased frequency for men with prostate cancer that has not spread.

"Reasons for this trend are not really known, but may include a desire to do something rather than do nothing on the part of both physicians and patients," Beer said. "Unfortunately, these men may be enduring significant side effects for an uncertain benefit."

Androgen deprivation therapy, also known as hormone therapy, is the gold standard of care for men whose prostate cancer is advanced and has spread throughout the body. The therapy works by shutting down male hormones, principally testosterone, that can promote prostate cancer growth. This common treatment for prostate cancer wipes out most male hormones found in the body. Side effects can be significant and include erectile dysfunction, hot flashes, fatigue, osteoporosis, high cholesterol, anemia, forgetfulness and insomnia.

Little is known about the effectiveness of hormonal therapy in men whose cancer remains localized within the prostate, so Beer and his colleagues decided to study data from the Prostate Cancer Outcome Study (PCOS). They presented their results on Saturday, Feb. 25, at the Prostate Cancer Symposium in San Francisco.

In the retrospective study, the research team examined demographic data, socio-economic factors and tumor biology in relationship to overall survival and cancer-specific survival for a subgroup of 276 PCOS subjects who had localized prostate cancer and received androgen deprivation therapy as their primary treatment. Between 1994 and 1995, a total of 3,486 men were enrolled in PCOS within six months of prostate cancer diagnosis.

The analysis showed that out all the demographic and socio-economic factors considered, overall survival was predicted only by age and certain features of prostate cancer. Tumor biology, which is measured by Gleason score, was the only independent predictor of cancer specific survival. Tumor mass as measured by PSA approached statistical significance as a predictor. Nearly 10 percent of men died from prostate cancer within 5 years of starting hormonal therapy.

"Our study indicates that cancer remains an important contributor to overall mortality in these men, particularly those with high Gleason score and high serum PSA," Beer said. "These data will be useful for men with localized prostate cancer choosing between aggressive treatments such as surgery or radiation, observation and androgen deprivation therapy."

In an earlier OHSU Cancer Institute study of the effectiveness of hormone deprivation as a primary therapy for localized prostate cancer, researchers found that younger men and those with higher-grade tumors are more likely to experience disease progression during treatment. They also found that men with localized prostate cancer on hormone therapy experience a higher than expected rate of bone fractures caused primarily by treatment-related osteoporosis.

"Studies suggest that more needs to be known about the risks and benefits of this treatment before we recommend it to patients with localized disease," Beer said.

Prostate cancer is the most common cancer in men and the second leading cause of cancer-related death in American men. Overall, 1 in 6 men will develop prostate cancer during his lifetime.

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This study was funded by the National Cancer Institute, a component of the National Institutes of Health.

Particulars:
Abstract No. 291: Predictors of Overall and Cancer-Specific Survival in Patients with Clinically Localized Prostate Cancer (PC) Treated with Primary Androgen Deprivation Therapy (PADT): Results from the Prostate Cancer Outcomes Study.

Authors: Julie N. Graff, Motomi Mori, Hong Li, Mark Garzotto, David Penson, Arnold Potosky and Tomasz M. Beer.

To access all OHSU news releases, visit www.ohsu.edu/news/


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