Sunday, March 20, 2011

Prostate Cancer and Androgen Deprivation Therapy

For a long time, the assumption was that prostate cancer was fueled by testosterone, or more specifically by a testosterone metabolite, 5-DHT (5{alpha}-dihydrotestosterone), and even today the first line approach to metastatic prostate cancer - and increasingly for even low risk cancers - is to completely suppress all androgen production (which has horrible side effects - increased risk of osteoporotic fractures, significant weight gain, gynecomastia, type-2 diabetes, stroke, cardiovascular events, and rare forms of sudden death).

Use of androgen deprivation therapy (ADT) as a first-line approach, however, does not improve survival rates, so considering the health risks and the cost, it's a foolish way to go.

"I think that the bottom line is that primary androgen-deprivation therapy does not appear to benefit the average man with localized prostate cancer," senior author Siu-Long Yao, MD, from the Cancer Institute of New Jersey, in New Brunswick, told Medscape Oncology. "It is possible that certain subsets of men, such as those with poorly differentiated cancer, might derive some benefit, but you must carefully consider and justify the rationale for primary androgen-deprivation therapy if you are going to proceed with it."

"My conclusion would be that primary androgen-deprivation therapy does not appear to be a good alternative to surgery or radiation; outcomes appear to be no better than conservative management or watchful waiting," Dr. Yao commented.

Here is a definition of ADT, just so we are clear:
Androgen deprivation therapy - androgen is a male sex hormone that promotes male sex development and characteristics, the major androgen is testosterone. Androgen deprivation therapy is treatment which suppresses the production of androgen (testosterone). Prescribing a GnRH (gonadotropin-releasing hormone) agonist is an example of androgen deprivation therapy, also known as ADT.
There is considerable evidence beginning to emerge that this cancer, like many others, is actually fueled by estrogen (see here, here, here, here, and here). If this is true, and more frequent research in this area suggests it is, then depressing androgens, which makes estrogen dominant, is the exactly opposite approach that should be taken. But it is still a complicated issue, since some estrogens seem to be beneficial while others are very harmful.

More precisely, prostate cancer seems to be fueled by androgen early in its development, with estrogens having changed the way the prostate cells function and respond to androgens, but by the time it has metastasized into bone (which is where the stem cells created by the cancer hibernate), it has become a primarily estrogen-fueled cancer.

If you are diagnosed with prostate cancer of any kind and the docs want to put you on androgen deprivation therapy - seek other opinions. I am not a doctor and I do not play one on TV, but I personally would not allow this form of treatment on me.

Anyway, the Medical Journal of Australia has released new guidelines for using ADT in non-metastatic prostate cancer, as reported by Medical News Today.

New Guidelines Developed For Patients With Low-Risk Prostate Cancer Who Are Receiving Androgen Deprivation Therapy

Men with prostate cancer who are being treated with androgen deprivation therapy are at increased risk of osteoporotic fractures, type 2 diabetes, and possibly, cardiovascular events, a new set of management guidelines states.

The guidelines, published in the Medical Journal of Australia, were developed to guide assessment and management of bone and metabolic health in men with non-metastatic prostate cancer who are being treated with androgen deprivation therapy (ADT).

The guidelines have been endorsed by the Endocrine Society of Australia, the Australian and New Zealand Bone and Mineral Society, and the Urological Society of Australia and New Zealand.

ADT is the standard first-line therapy for men with metastatic prostate cancer - cancer that is spreading to other organs - but is increasingly being used for men with non-metastatic cancer.

Dr Mathis Grossmann, Senior Research Fellow in the Department of Medicine at Austin Health/Northern Health at the University of Melbourne, and co-authors recommended counselling patients about possible risk factors before starting treatment, an individualised, multidisciplinary approach for each patient, and regular testing for bone mineral density and metabolic risk factors.

Dr Grossmann said that prostate cancer was the most common solid organ cancer in Australian men, with 20,000 new cases being diagnosed in Australia each year.

"The prevalence of prostate cancer is increasing because the population is ageing and prostate-specific antigen testing is occurring more frequently," Dr Grossmann said.

"This has led to a profound shift towards detecting more clinically localised, low-risk prostate cancer.

At the same time, the rate of use of ADT in men with non-metastatic prostate cancer has increased, with an estimated 23,500 men being treated in Australia during 2008-09.

Dr Grossmann said that the expanded use of ADT in non-palliative treatment mandated a proper risk-benefit assessment in a multidisciplinary fashion.

The developers of the guidelines called for controlled trials to better define the risk-benefit ratio of ADT.

"Such information will help to avoid overuse of ADT, especially for men who have a high baseline risk of fractures and cardiovascular events but low-risk prostate cancer," they said.

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