Newswise — Results of a study at Roswell Park Cancer Institute (RPCI) support taking a revised view of prostate cancer and how best to treat it. Almost all advanced prostate cancer responds well at first to androgen deprivation therapy but the cancer recurs with a poor prognosis. This study suggests that these cases might need to be managed in a different way. The research was led by James L. Mohler, MD, Chair of the Department of Urologic Oncology at Roswell Park Cancer Institute (RPCI), and involved colleagues at the University of North Carolina. The results were published in the January issue of Clinical Cancer Research.
Advanced prostate cancer is often treated by hormonal treatment or surgical castration, either of which effectively removes the testicles to deprive the body of androgens (male hormones produced by the testicles). After remissions of months to several years, almost all prostate cancer recurs as what is currently called androgen-independent disease. Researchers have believed that these secondary tumors no longer require androgens to grow and have attempted to develop therapies based on that assumption, often with little success.
However, this research by Dr. Mohler and colleagues indicates that these recurrent prostate cancers have found a way to make the equivalent of testicular androgens directly from cholesterol or from weaker androgens made by the adrenal glands. "These findings will cause everyone in the field of prostate cancer to re-evaluate how they think about advanced prostate cancer," said Dr. Mohler. "We suggest that these advanced prostate cancers still depend on androgens for growth and they should be called recurrent and not androgen-independent."
The study compared prostate cancer specimens from 22 men whose prostate cancer recurred locally after surgical castration to samples from benign prostate specimens from 48 men who had received no prior treatment.
The researchers used immunohistochemistry and image analysis and found evidence of androgen receptor protein stabilization and high levels of tissue androgens " testosterone and dihydrotestosterone "in the samples with recurrent prostate cancer. "We believe that these androgens also activate the androgen receptor since we found that the tissue also contained high levels of the classic androgen-regulated gene product, prostate specific antigen or PSA," continued Dr. Mohler. The prostate specific antigen (PSA) serum test- pioneered at Roswell Park Cancer Institute (RPCI) in the late 1970s " revolutionized prostate cancer detection and management. Elevated PSA levels are suggestive of cancer development.
"Novel therapies that target the androgen receptor directly and prevent the formation of androgens within prostate cancer tissue may offer the most effective approach to prolonging remission or reinducing remission of recurrent prostate cancer," notes Mohler.
Roswell Park Cancer Institute, founded in 1898, is the nation's first cancer research, treatment and education center and is the only National Cancer Institute-designated comprehensive cancer center in Upstate New York. For more information, visit RPCI's website at http://www.roswellpark.org.
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