Metastatic Prostate Cancer and Testosterone

Advanced, or metastatic, or "high-risk", prostate Cancer is traditionally difficult to treat. Most metastatic cancers are hard to treat.

Metastasis generally defines the boundary between benign and aggressive tumors. Some tumor cells develop the ability to detach themselves from the tumor itself, move into the blood stream, and travel to distant parts of the body, where they settle and multiply.

As long as the cells are all in the same physical location, there may still be options for direct treatments like surgical removal, radiation treatment, and cryo-treatment. For the prostate, these are often called "low risk" tumors.

Please keep in mind that there are significant differences between individuals, at least as great as the gross physical differences we all know. The same is true of Cancers. It is easier to discuss the statistics than individual cases, because there are such a wide range of possibilities. No matter what the statistics are, they don't make any difference whatsoever to one individual case. It is very difficult to make a diagnosis with extreme precision on any one individual, before actually applying the scalpel.

From the literature, it appears that pre-metastatic cancer is qualitatively different from advanced cancer.

The distinction is so clear-cut that it might be appropriate to treat and discuss them as wholly separate diseases.

An effective treatments for one type can be an accelerant for the other.

Something that low-risk and high-risk cancers have in common is a requirement for Testosterone.

The various methods of castration - surgical, chemical, vaccination, all serve to dramatically lower the serum testosterone levels. Prostate cells, and low-risk prostate cancer cells, need testosterone to be present. In its absence they can and do die. For castrates, the prostate cells and low-risk prostate cancer cells commit cell suicide - apoptosis. Not all at once, of course, but progressively. Long term castrates experience distinct and substantial shrinkage of the prostate. Again, your mileage will vary, with no "might" about it.

http://ajp.amjpathol.org/cgi/content/ab ... 368?ck=nck

Treating high-risk prostate cancers with Testosterone causes a significant increase in their growth rate. The effect can be so great that castration paradoxically risks the patients life, what is left of it.

http://clincancerres.aacrjournals.org/c ... l/12/1/169

The effect is called tumor flare, and has been remarked upon by other posts on this site, directly and indirectly.

http://prostatecancer.about.com/od/trea ... herapy.htm

http://www.prostate-cancer-institute.or ... erapy.html

When the serum levels of Testosterone are reduced by some drugs the pituitary, in a feedback mechanism, tries to compensate by producing more GnRH, the signal to produce Testosterone. This drives the adrenal glands to over-produce Testosterone and flooding the body with it. If high-risk tumor masses are in close proximity to critical functions - the heart or arteries for example - then rapid high-risk tumor growth can interfere with proper function, possibly enough to kill the patient.

It would seem that near elimination of Testosterone would be the perfect solution, yet the effect of reducing Testosterone to anorchic (castrated) levels has, at most, a temporary effect on high-risk cancer.

Further investigation has revealed that high-risk prostate cancers, in the absence of Testosterone, will develop the ability to produce their own Testosterone locally, within the tumor. After an initial phase of shrinkage and cell death through apoptosis, the cancer comes back.

High-risk prostate cancers often develop multiple receptors on their external surfaces to more effectively detect the Testosterone signal. When the sensitivity of the tumor goes up a hundred- or a thousand-fold, treatments to reduce serum Testosterone levels by only 98% seem to be frivolous.

Also, for some high-risk prostate cancers, the Testosterone receptors themselves are degraded. The result is that they are promiscuous in their recognition of steroid-like compounds, and may begin to trigger on steroids like Estrogen, or some of the blocking medications. The medication itself can begin to promote the cancer.

In contrast to the regulated system in the body where the pituitary produces GnRH in response to Testosterone levels, and the testes produce Testosterone in response to GnRH levels, the high-risk prostate cancers self-regulate - they produce the Testosterone, and then detect it. No amount of interference in the normally regulated system can affect the self-regulated tumor cells.

The paradox is explained. High-risk tumor cells need Testosterone. When they don't get it from their environment, they produce it themselves.

http://www.eurekalert.org/pub_releases/ ... 052708.php

http://www.urotoday.com/61/browse_categ ... ot_androge nindependent__abstract.html

http://cancerres.aacrjournals.org/cgi/c ... 68/11/4447

http://www.modernmedicine.com/modernmed ... ryId=40237

Reading an reviewing all this suggests to me that tumor masses of high-risk prostate cancer contain minute populations of testosterone producing tumor cells. Left alone, rapidly growing tumor cells soon bury the minor population of Testosterone producers, minimizing their access to nutrients.

However, once Testosterone levels are radically decreased, the majority of tumor cells die off, leaving the Testosterone producers to continue. The patient improves temporarily, but only until the population of tumor cells once again rises to a level that threaten the patient's life and well-being.

Thank you for the information. I am at an age when this is a matter of interest.

This is indeed interesting information. I am know too many men who have died from this form of cancer.

Thanks. Very interesting and helpful.

Joe,

With cancer of the prostrate being such an issue, what are the pros and cons of just having the prostate removed before cancer sets in?

It is possible (no guarantee) to remove the prostrate without damaging the nerves that control erections (assuming one can otherwise get, and want to get, erections) :

http://www.njurology.com/RoboticSurgery ... emoval.php

(includes graphic video of a prostrate being removed without damaging penile nerves.....or so they say).

Obviously risks and costs are always a downside of having any surgery, and insurance would not cover preventative removal of a healthy prostate. But if erections (if desired) could be maintained, what other pros/cons of voluntary removal of a healthy are there? Not that this is the same thing as removing tonsils, but again since sperm can be removed from healthy testicles....if needed..... why not get rid of a potential cancer risk by removing an unnecessary body part?

For any natural male with a prostate who is receiving testosterone therapy (for whatever reason) it would seem that, especially when one is older, voluntary removal of the prostate might be a way to eliminate the risk of prostate cancer.

My father had prostate cancer and I don't want to have to go through what he went through. As a person who is on testosterone replacement therapy, because of non-functioning testicles, I would rather stop the therapy and/or have preventative prostate removal surgery and castration than go through prostate cancer. This would be very drastic insurance, but eliminating the risk of prostate cancer would be worth it to me (not to everyone)

Lastly, for people who have natural normal testosterone levels, but who loose the ability to get erections as a result of cancerous prostate removal surgery, just what kind of mental and physical problems result from that? Seems like it would be like having no penis but still be desirous of sexual gratification but unable to obtain it; yikes - that's a scary thought.