ADVANCED PROSTATE DISEASE

How is advanced prostate cancer treated?

If the prostate cancer has been confirmed as an aggressive cancer and has spread to other parts of the body, the doctor may recommend hormone therapy in combination with surgery or radiotherapy. Hormone treatment can be used to control prostate cancer when the cancer has spread beyond the prostate or ‘metastasized’.  Hormone therapy may also be recommended when the cancer returns again after initial surgery or radiotherapy.

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What is hormone therapy?

The growth of both normal and most cancerous prostate cells depend on the androgen, dihydrotestosterone (DHT). Dihydrotestosterone is produced from testosterone, therefore by stopping the normal production of testosterone in the body, DHT is no longer available in the body to stimulate the growth of the prostate cancer.

Testosterone is produced mainly in the testes by the Leydig cells and small amounts are also made by the adrenal glands which are walnut sized glands that sit on top of the kidneys. Treatment to stop the production of testosterone is focused on stopping or reducing the production at these sites. Testosterone levels can be reduced by either surgical removal of the testes (orchidectomy) or by medication that stops testosterone production by other mechanisms. Although surgical removal of the testis is a relatively simple operation, some men prefer other treatments. Hormone therapy acts by either:

• Stopping the production of testosterone;
• Blocking the action of testosterone and DHT on tissues.

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Stopping the production of testosterone

The production of testosterone by the testis is controlled by the pituitary gland. This is a small gland that is linked to  the base  of the brain, near an area called the hypothalamus. The pituitary releases a number of messenger hormones that act as the “keys” to activate different organs in the body, including the testes.

The pituitary gland produces luteinizing hormone (LH) and follicle stimulating hormone (FSH) which are the two important hormones that stimulate and maintain the function of the testes.

In turn, the pituitary is controlled by hormones that are produced by the hypothalamus. The hormone that controls the production of the pituitary hormones LH and FSH is called gonadotrophin-releasing hormone (GnRH).

Blocking the action or production of GnRH would lower LH levels which in turn would stop the production of testosterone in the testes. Some forms of hormone therapy to stop the production of testosterone, and therefore lowering DHT levels, act by blocking GnRH stimulation of LH secretion. The drugs Lucrin®, Zoladex® and Eligard® which are usually given as monthly injections, act in this way.

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Blocking the action of testosterone

Another way to stop the action of testosterone and dihydrotestosterone is to stop these hormones from being recognised by their sensors (androgen receptors) which are located on many organs, including the prostate. Androgen receptors detect testosterone and DHT. Drugs called anti-androgens, which are given by tablet orally, act to block the interaction of testosterone and DHT with the androgen receptors. There are a number of anti-androgens available in Australia and the most common ones include:

• Androcur® (cyproterone);
• Cosudex® (bicalutamide).

Both types of hormone therapy may be given either continuously or in some instances in cycles where treatment is started and stopped repeatedly (called intermittent hormone therapy). Measurement of PSA levels is a useful way of monitoring the growth of prostate cancer and is used to decide when intermittent hormone therapy should be stopped and then started again. Although intermittent hormone therapy can reduce the side-effects, it is unclear whether this form of treatment is more effective than continuous treatment in controlling the growth of the prostate cancer.

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What are the side-effects of hormone therapy?

Side-effects of hormone therapy happen because other organs in the body are also dependant on testosterone for their function. Most men will develop a lack of interest in sexual activity (reduced libido) and the ability to have erections. When considering hormone therapy, it is often helpful to discuss with your wife or partner the effect of treatment on your sexual relationship.

Other common side-effects include hot flushes, tiredness and sweating, gradual decrease in body hair, reduced bone and muscle strength and cognitive changes.  Liver function may be affected with oral medications and some men gain weight and develop some breast enlargement. Over a longer period of time, there may be a loss of calcium from the bones leading to fragile bones (osteoporosis) and fractures.

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What is hormone resistance?

The ability of hormone therapy to control prostate cancer varies between men. About 30% of prostate cancers will shrink while 30% may not grow any further. About 1 in 5 men experience continued growth of the prostate cancer within a year of starting treatment, despite hormone therapy.,

When prostate cancer no longer responds to hormone therapy and growth of the prostate cancer continues, it is called hormone resistant prostate cancer. Hormone resistance and re-growth of prostate cancer may become evident over time, even if the prostate cancer initially responded to hormone therapy. However, about 10% or less may have no sign of re-growth of prostate cancer during 10 years of hormone treatment. Measurement of PSA levels is used to monitor the response to hormone treatment and, subsequently, progression of prostate cancer.

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What are the treatments for hormone resistant prostate cancer?

Treatment of hormone resistant prostate cancer is aimed at palliation or treating symptoms.  This may include:

• Radiotherapy
  which can be given locally to any other site where the prostate cancer has spread to relieve the pain. External beam radiotherapy is usually given. 
• Bisphospohonates
  are often given to help reduce bone loss with hormone treatment and to lessen the chance of secondary cancers developing in the bones.
• Steroids
  such as synthetic cortisone drugs called prednisolone may sometimes be helpful to control pain.
• Pain relief
  using a variety of medications is an important part of the management of patients with uncontrolled prostate cancer growth.
• Chemotherapy
  in certain cases may help with quality of life.  Chemotherapy is not a major area of success but recent research has identified one drug, docetaxel, which has been reported in trials to produce a modest improvement in survival and quality of life in men with advanced prostate cancer.
• Clinical trials
  using new approaches are continually being undertaken. These have to provide benefits comparable with the state-of-the-art management for patients to be approved, and often are able to offer new treatments, albeit in a research setting, which are not otherwise available. However, it is important for patients to understand that these are experimental therapies and, although hopefully they will, they may not benefit men volunteering in the trial.

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