New View of Recurrent Prostate Cancer

Novel therapies for recurrent prostate cancer should target androgen receptor directly and prevent the formation of androgens within prostate cancer tissue.

PSA Rising /New York/ February 4, 2004 -- Results of a study at Roswell Park Cancer Institute (RPCI) support taking a revised view of prostate cancer and how best to treat it, the study's investigators say.

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.

Advanced prostate cancer is often treated by hormonal treatment or (more rarely today) by surgery called orchiectomy (removal of the testes). Either of these treatments effectively deprives 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 (also called hormone-refractory).

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.

This new research by James L. Mohler, MD, Chair of the Department of Urologic Oncology at Roswell Park Cancer Institute (RPCI) 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.

James L. Mohler, MD is Chair of the Department of Urologic Oncology at Roswell Park Cancer Institute (RPCI). He works with colleagues at the University of North Carolina. Their results were published last month in Clinical Cancer Research, 2004 Jan 15;10(2):440-8 under the title: The androgen axis in recurrent prostate cancer.

This page made by J. Strax, Feb. 14, 2004. Last modied Nov 15, 2004.