How Highs and Lows in Testosterone Levels ‘Shock’ Prostate Cancer Cells to Death


“Munich, Germany: A strategy of alternately flooding and starving the body of testosterone is producing good results in patients who have metastatic prostate cancer that is resistant to treatment by chemical or surgical castration, according to new findings.
“In a presentation at the 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Munich, Germany, today (Thursday), researchers reported that results from 47 men who have completed at least three cycles of bipolar androgen therapy (BAT) showed that the strategy was safe and effective. Prostate specific antigen (PSA) levels fell in the majority of the men, tumours shrank in some men, in several the disease did not progress and this included some whose disease continued to be stable for more than a year. One man appears to have been ‘cured’, in that his PSA levels dropped to zero after three months and have remained so for 22 cycles of treatment, with no trace of the disease remaining. The researchers are planning to treat a group of 60 men in total.”

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Comparing Chemical and Surgical Castration for Prostate Cancer

“Surgical castration to remove the testicles (orchiectomy) of men with metastatic prostate cancer was associated with lower risks for adverse effects compared with men who underwent medical castration with gonadotropin-releasing hormone agonist (GnRHa) therapy, according to an article published online by JAMA Oncology.

“Androgen-deprivation therapy (ADT), which is achieved through surgical or medical castration, has been a cornerstone in the management of  (PCa) for the past 50 years. But the use of bilateral orchiectomy has been nearly eliminated in the U.S. because of cosmetic and psychological concerns.

“Quoc-Dien Trinh, M.D., of Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Boston, and coauthors compared adverse effects of GnRHa and bilateral orchiectomy in 3,295 men with metastatic PCa (66 or older) between 1995 and 2009. The authors analyzed six major adverse effects, which were picked based on their effect on a patient’s quality of life, the potential for increased health care costs, and on a previously described association with ADT use. The six  were: any fractures, peripheral artery disease, venous thromboembolism, cardiac-related complications, diabetes and cognitive disorders.”

Study Discounts Testosterone Therapy for Early Prostate Cancer

“For decades, millions of men with early prostate cancer have been placed on drug therapy to suppress their production of testosterone, despite such significant side effects as impotence, diabetes and bone loss. Now a large new analysis has concluded that so-called androgen deprivation therapy does not extend the lives of these patients.

“ ‘There are so many side effects associated with this therapy, and really little evidence to support its use,’ said Dr. Grace L. Lu-Yao, a researcher at the Rutgers Cancer Institute of New Jersey and the lead author of the report, published on Monday in JAMA Internal Medicine. ‘I would say that for the majority of patients with localized prostate cancer, this is not a good option. ”

“Dr. Lu-Yao and her colleagues followed tens of thousands of men with early prostate cancer for as long as 15 years and found that those who received androgen deprivation therapy lived no longer on average than those who did not. The study joins a growing body of evidence indicating that for many men with early prostate cancer, avoiding testosterone-suppressing drugs altogether may be better than grappling with their potentially devastating toll.”

“One expert who was not involved in the new study, Dr. James M. McKiernan, acting chairman of urology at NewYork-Presbyterian Hospital/Columbia University Medical Center said its findings were ‘eye-opening and even alarming.’ ”

Image: Credit Stuart Bradford

PSMA-Based Imaging Traces Even Treatment-Resistant Prostate Cancer

“Anti-androgen hormonal therapy, also called chemical castration, can be an important defense against further disease progression for patients with prostate cancer that has traveled and grown in other areas, or metastasized—but some cases simply do not respond to this treatment. A groundbreaking molecular imaging agent has been developed to help clinicians find as much cancer as possible, whether it is responding favorably or not, in an effort to improve clinical decision making for these patients, say researchers at the Society of Nuclear Medicine and Molecular Imaging’s 2014 Annual Meeting.”

A Road Map to Comprehensive Androgen Receptor Axis Targeting for Castration-Resistant Prostate Cancer

“Gonadal androgen suppression (castration via orchiectomy or gonadotropin-releasing hormone analogues) suppresses circulating testosterone levels but does not achieve adequate androgen ablation within the prostate cancer microenvironment because it does not address adrenal and intratumoral steroid contributions. These residual extragonadal sources of androgens allow prostate cancer cells to survive, adapt, and evolve into castration-resistant prostate cancer (CRPC). The persistent significance of the androgen receptor (AR) axis in CRPC was recently validated by the clinical efficacy of androgen synthesis inhibitors (abiraterone) and novel, second-generation AR antagonists (enzalutamide). The appreciation that conventional therapeutic approaches achieve a suboptimal ablation of intratumoral androgens and AR axis signaling output opens transformative therapeutic opportunities. A treatment paradigm of comprehensive AR axis targeting at multiple levels (androgen synthesis, metabolism, and action) and at all relevant sites (gonadal, adrenal, intratumoral) simultaneously at the time of initiation of endocrine therapy (instead of the current approach of sequentially adding one agent at a time and only after disease progression) deserves examination in clinical trials to explore whether maximal first-line AR axis suppression via combination therapy can achieve maximal induction of cancer cell apoptosis (before they have the chance to adapt and evolve into CRPC) and thus, improve patient outcomes.”