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

Excerpt:

“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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Common Prostate Cancer Treatment Linked to Later Dementia

Excerpt:

“A new retrospective study of patient medical records suggests that men with prostate cancer who are treated with testosterone-lowering drugs are twice as likely to develop dementia within five years as prostate cancer patients whose testosterone levels are not tampered with.

“The study, by researchers at the Stanford University School of Medicine and the University of Pennsylvania Perelman School of Medicine, also demonstrates emerging techniques for extracting biomedical data from ordinary patient medical records.”

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Testosterone-Related Genetic Mutation Leads to Deadlier Outcomes In Prostate Cancer

Excerpt:

“A team of Cleveland Clinic-Mayo Clinic researchers has shown for the first time that patients with advanced prostate cancer are more likely to die earlier from their disease if they carry a specific testosterone-related genetic abnormality.

“The findings, published in the September 2016 edition of The Lancet Oncology, suggest that a specific, inherited polymorphism, or inherited genetic change, in the HSD3B1 gene renders standard therapy for metastatic prostate cancer less effective. The researchers anticipate that the findings will lead to a simple blood test to detect the presence of the polymorphism, personalizing cancer treatment and indicating which patients may need more aggressive treatment.”

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'Bipolar' Therapy: New Twist in Advanced Prostate Cancer

“Preliminary data suggest that a new twist on manipulating hormones in prostate cancer shows some benefit. The standard approach to treatment is androgen deprivation therapy (ADT), but the new approach intersperses this with bipolar androgen therapy (BAT) with intramuscular testosterone injections.

“Results from a small phase 2 study in 29 men with advanced hormone-sensitive prostate cancer show that the primary endpoint was met, with nearly 60% of men achieving a prostate-specific antigen (PSA) level <4 ng/mL after undergoing two cycles of BAT.

“The findings, which were presented at Genitourinary Cancers Symposium (GUCS) 2016, also suggest that BAT may have a positive impact on quality of life.”


Meta-analysis: Testosterone Is Not a Risk for Prostate Cancer, But…

“Testosterone, whether occurring naturally or taken as replacement therapy, does not cause prostate cancer or spur increases in prostate-specific antigen (PSA) levels in men, according to a new meta-analysis.

“The results are ‘encouraging,’ but longer-term data from randomized trials are needed to strengthen the finding, said lead author Peter Boyle, PhD, DSc, who is president of the International Prevention Research Institute in Lyon, France

” ‘You need 15 to 20 years of follow-up to see true prostate cancer risk,’ he told Medscape Medical News here at the American Urological Association 2015 Annual Meeting.

“The average follow-up in the studies included in the meta-analysis is ‘much less’ than what is needed, he said.”


Low Testosterone During First Year of ADT Linked to Improved Survival

“In an analysis from the PR-7 trial reported in the Journal of Clinical Oncology, Klotz et al found that in men with prostate cancer with biochemical failure after radiotherapy with or without surgery, a nadir serum testosterone level ≤ 0.7 nmol/L during the first year of continuous androgen-deprivation therapy was predictive of improved cause-specific survival and prolonged time to hormone resistance.

“In the PR-7 trial, 1,386 patients were randomly assigned to continuous androgen-deprivation therapy (n = 696) or intermittent androgen-deprivation therapy (n = 690). Of 626 men in the continuous androgen-deprivation therapy group eligible for the current analysis, 226 developed castration-resistant prostate cancer, with a median time to diagnosis of 10.0 years; the 5-year event-free rate was 69%…

“The investigators concluded: ‘Low nadir serum testosterone (ie, < 0.7 nmol/L) within the first year of androgen-deprivation therapy correlates with improved [cause-specific survival] and duration of response to androgen deprivation in men being treated for biochemical failure undergoing [continuous androgen deprivation].’ ”


Testosterone Levels During ADT May Predict Prostate Cancer Outcomes

“A strong reduction in testosterone levels during the first year of androgen deprivation therapy (ADT) correlates with an improved survival in prostate cancer patients undergoing treatment for biochemical failure.

“Men with prostate cancer who had testosterone levels ≤ 0.7 nmol/L had significantly longer survival and longer time to hormone resistance compared with men with higher testosterone levels (P = .015 and P = .02, respectively). Men who had testosterone levels consistently > 0.7 nmol/L had a greater risk of dying from their prostate cancer compared with men with lower hormone levels.

“Those whose testosterone levels increased to ≥ 1.7 nmol/L developed castration resistance more quickly, compared with men whose hormone levels remained steadily ≤ 0.7 nmol/L.

“The current analysis led by Laurence Klotz, MD, of Sunnybrook Health Sciences Centre at the University of Toronto, and colleagues analyzed the prospectively collected testosterone levels and clinical outcomes of the 1,386 men enrolled in the phase III PR-7 trial, which randomized men with biochemically recurrent prostate cancer after primary local therapy to receive either continuous (n = 696) or intermittent (n = 690) ADT…

“But, the editorial authors believe that caution is warranted in interpreting these post hoc results because ‘the primary analysis of the PR-7 study showed that intermittent hormone therapy was non-inferior to continuous therapy with respect to overall survival.’ Therefore, the importance of the further manipulation of testosterone levels in prostate cancer patients after ADT is still unclear. They also point to an ongoing trial, the SWOG-S1216 trial, which is currently evaluating the role of deeper testosterone suppression. ‘Until these or similar results are available, we should not recommend deeper androgen suppression in the first-line setting for men with (metastatic or nonmetastatic) hormone-sensitive prostate cancer,’ concluded Suzman and Antonarakis.”


Now BATting: A New Treatment Approach That Uses Testosterone First, Then ADT


Androgen deprivation therapy (ADT) has long been a mainstay in the management of prostate cancer. Indeed, the vast majority of prostate cancers depend on androgens (hormones like testosterone) for their growth. Lowering testosterone levels with ADT is a reasonable approach. But it comes with two sets of problems. Continue reading…


Strategy Might Thwart Resistance to a Common Prostate Cancer Treatment

“Conventional wisdom has it that high levels of testosterone help prostate cancers grow.”However, a new, small study suggests that a treatment strategy called bipolar androgen therapy—where patients alternate between low and high levels of testosterone—might make prostate tumors more responsive to standard hormonal therapy.

“As the researchers explained, the primary treatment for advanced prostate cancer is hormonal therapy, which lowers levels of testosterone to prevent the tumor from growing. But there’s a problem: Prostate cancer cells inevitably overcome the therapy by increasing their ability to suck up any remaining testosterone in the body.

“The new strategy forces the tumor to respond again to higher testosterone levels, helping to reverse its resistance to standard therapy, the researchers say.

“If confirmed in several ongoing larger trials, ‘this could lead to a new treatment approach’ for prostate cancers that have grown resistant to hormonal therapy, said lead researcher Dr. Michael Schweizer, an assistant professor of oncology at the University of Washington School of Medicine in Seattle.”