Sunday, July 17, 2016

Why Do So Many Men Opt For Castration To Treat Prostate Cancer?


A PET-scan showing extent of bone metastases in a prostate cancer patient. Each dark area represents an agglomeration of actual prostate cancer cells, i.e. in the spine, pelvis, neck etc. If the spread and growth isn't stopped, bones will fracture, spinal discs compress and pain will be constant and excruciating.


Let's concede that once one joins a cancer support group, say for prostate cancer, there is a high probability he will learn about more horrors and fallout from the disease (and its treatments) than he'd normally care to process. Or accept! That also goes for one's wife, who may have to face the consequences of the disease and its treatments along with the patient.

In the support group to which I belong, I recently came across a post by a 68 -year old who bragged he'd added "15 years or so" to his life by resort to an orchiectomy.  On googling the term I learned it meant none other than surgical castration, i.e. the surgical removal of one's testicles leaving the scrotum full of mainly empty space. (Though we are informed "artificial plastic balls can be inserted if the patient desires to give a more natural sensation.")  When I read the guy's post I thought he had lost it: who would rather live life as a half-man, a eunuch basically, just to gain some extra time from prostate cancer? It turns out a lot of guys!

The relevant University of California At San Francisco  (UCSF) document on hormone therapy has billed  the orchiectomy "as the least expensive form of hormone treatment".  It effectively reduces testosterone - the main fuel for prostate cancer- by removing the testes a prime source. Specifically, the effect is almost immediate with testosterone levels plummeting to what is known as "castrate level" within 12 hours.

 The other alternative is chemical castration, which is used when a patient doesn't want to end up physically de-balled,, given it can have "devastating emotional consequences".  (Well, I will say it has to be enormously difficult walking around with an empty ball sack.)  Anyway, in chemical castration one is given one or more medications including casodex, flutamide and finestride.

The medical castration route takes advantage of the chemical-hormone pathways which begin in the hypothalamus with the secretion of luteinizing hormone-releasing hormone  (LHRH) which in turn stimulates the pituitary gland  to produce luteinizing hormone (LH) as well as follicle -stimulating hormone (FSH) . Then LH signals specialized cells in the testicles to secrete testosterone into the bloodstream. When testosterone reaches the prostrate it is converted into di-hydrotestosterone (DHT) a much more potent form of testosterone, via the action of an enzyme:5 -alpha reductase. The objective of medical castration then is to break this cycle, usually in one of two ways: 1) via  LHRH agonists or 2) LHRH antagonists.

In (1) the medication stops the testicles from making testosterone. This is achieved by inducing a continuous message from the brain to produce testosterone which over-stimulates the testes. They respond by being "overworked" so switch off.

In (2) the medication also induces the testes to stop producing testosterone but not by over stimulation (which can trigger a testosterone "flare"(or spike, including uncomfortable side effects) before the level subsides.

The differences between the assorted chemical castration agents and their effects are discussed here for those interested:

https://www.youtube.com/watch?v=KtIfsvQh2qI

In thirty percent or more of these administrations, one of the primary side effects is a condition called gynecomastia which is briefly outlined via one case in this issue of The New England Journal of Medicine. I warn all males, especially those now taking 'high T' supplements or shots, this may well be your future as I will show below!

http://www.nejm.org/doi/full/10.1056/NEJMicm1209166#t=article


Of course, there are sundry other side effects from either surgical or chemical castration, but this one stands out because....well....it's fucking humiliating to be walking around with a pair of man boobs! Also, that they may have to be treated at regular intervals using drugs like tamoxifen or procedures including liposuction (to extract extra glandular tissue) or partial mastectomy.  If you think I am kidding about this, do some googling on your own, starting with the phrase "gynecomastia and prostate cancer" or "gynecomastia and anti-androgen therapy".

The pain and/or sensitivity can be so pronounced that some medical centers which offer castration - surgical and chemical  - say like UCSF, advise patients to get "prophylactic" treatment before commencing hormone treatment. According to a UCSF document:

"This condition arises from a hormone imbalance resulting for a more dominant role for estrogen in a man's body once treatment begins. It occurs more commonly with anti-androgen drugs than with LHRH (luteinizing hormone-releasing hormone )  medications.

We recommend a single dose of radiation to both breasts at the start of treatment."

The dose of radiation is usually 8 Gy delivered by external beam to each nipple. Most guys complain about a "burned" sensation, and needless to say are in no mood for sex afterwards or anyone getting near their nipples or tweaking them. (Of course, the other general side effect of such therapies is to lower libido until when you're shown a Hustler honey in the nude, you have about as much reaction as to an old rocking chair.)

The latest take on hormone treatment is to recommend postponing it until prostate cancer metastases or "mets" appear in the bones. (See e.g.  Paller and Antonarakis: ' Management of Biochemically Recurrent Prostate Cancer After Local Therapy: Evolving Standards of Care and New Directions' ) 

 The reasons for such delay  take into account emergence of  "comorbidities" or hugely negative treatment outcomes, including not only gynecomastia but also a 50 percent higher risk of developing Type II diabetes because the therapy generates weight gain and with it, insulin resistance or metabolic syndrome. You can learn more from this youtube video about the need to treat especially once bone mets appear::

https://www.youtube.com/watch?v=GFHUCnwox7o

It is important to note from this how prostate cancer cells actually grow and develop inside bones and can lead to "skeletal events" that are catastrophic including fractures, and compression of the spinal cord..  The doctor here is referring to radio-pharmaceutical options but this is usually given in late advanced prostate cancer. For early AD treatment, i.e. after "mets" have first appeared, one would go with hormone therapy, anti-androgen therapy etc. See e.g.   https://www.youtube.com/watch?v=0aN0wrjS7_c

And:

https://www.youtube.com/watch?v=PGeFM9ofliA&list=PLu6CZL-_j8BbnvufjBIkBb2TH8f2QbZY4

Given that one absolutely doesn't want to become crippled or saddled with multiple fractures in his last days, i.e. via spread of bone mets, it looks as though I will have to choose some type of hormone therapy. This is assuming my MRI fusion biopsy shows Gleason scores and undifferentiation associated with the lesions detected in the MRI. This would likely not be commenced until bone mets appear, such as on a pet scan, CT-scan or MRI.

This choice would allow at least 10 years,  maybe longer,  for a relative quality of life until the end phase begins with castration resistance, meaning the testosterone plummets but the PSA continues to increase. In other words, hormone treatment ceases to be effective.  As Dr. Charles Ryan points out in the superb UCSF lecture which follows, the prostate cancer cells are capable of making their own testosterone, and hence driving the prostate specific antigens higher.. This "will to survive" marks the challenge of confronting all types of cancer.

To see the detailed UCSF lecture on treating prostate cancer with androgen deprivation and other hormone treatments go to:

https://www.youtube.com/watch?v=kQ4im2WQ75E


See also this basic discussion of how prostate cancer occurs.

https://www.youtube.com/watch?v=7_5MnsdQeQs

I do hope this blog post will be helpful for other guys facing this disease.

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