5. Prostate Cancer: Hormonal Therapy

• Introduction
• When is hormone treatment used?
• What does hormone treatment involve?
• What are the current medications available in Australia?
• What are the side effects of hormone treatment?
• A word about hormonal therapy
• Hormone resistance: what if the treatment stops working?
• Is chemotherapy an option?
• What about additional therapies?

Introduction

Information sheet number 3 in this series talked about the importance of stage, or how far the cancer has spread, when deciding the best type of treatment. In information sheet number 4, we talked about recurrence of cancer after surgery or radiotherapy, and how this is monitored. Hormonal therapy is the major treatment option for cancer which has already spread beyond the prostate region, or has recurred following initial treatment by surgery or radiotherapy. It is also sometimes used for short periods in combination with radiotherapy. This information sheet describes what hormonal therapy is, its effects and the long term outcome.

Male hormones (also called androgens)are important for prostate growth - a fact which has been known for over 50 years. Indeed the normal development of the prostate to its adult form is very dependent on testosterone, the principal male hormone released from the testicles. Men rely on normal levels of male hormones to have adult sexual function and fertility. The level of male hormone in the body is precisely controlled by several factors, the main one being the normal secretion of stimulatory hormones from the hypothalamus and the pituitary gland in the brain.

Both normal or benign cells in the prostate and prostate cancer cells are stimulated to grow by male hormones. Prostate cancer cells that have left the prostate and are growing in other areas of the body (metastases) are also stimulated to grow by male hormones. Consequently one relatively common treatment for prostate cancer which has spread outside the prostate region (see information sheets numbers 3 and 4) is to lower the levels of male hormones in the body and thereby stop the growth of cancer cells. This happens irrespective of whether the cells are in the prostate or in other areas of the body. Indeed, prostate cancer cells typically respond to the withdrawal of male hormones by dying. Unfortunately, not all prostate cancer cells die, and with time, often several years later, the cancer returns. Nevertheless, good cancer control and a symptom-free lifestyle can be achieved for many years by men on hormone therapy. This information sheet is designed to assist those with prostate cancer for whom hormone treatment is an option.

When is hormone treatment used?

This is not a simple question to answer, for many factors need to be considered prior to choosing this treatment option. In general, hormonal therapy is used when there is evidence that the cancer is no longer confined to the prostate (and sometimes to shrink the gland prior to removal or radiotherapy).

Commonly hormone treatment is used for men in whom radical treatments have not succeeded in curing the disease, ie following radical surgery or radiotherapy. Often our best indicator of recurrent prostate cancer growth is from a rising PSA level (PSA is a blood test which, after surgery or radiotherapy, indicates the amount of cancer activity still remaining in the body - see information sheets 2 and 4). The exact timing of hormone treatment in response to a rising PSA level is variable and based to some extent on the speed of tumour growth and the sites of the tumour.

Hormone treatment is also the principal therapy for metastatic prostate cancer when the prostate cancer cells have escaped from the prostate to grow in other sites of the body. In this case, the treatment may be started soon after this diagnosis is made, although on occasions a delay in starting does not pose serious risk to the patient.

Hormone therapy may also be used to shrink the tumour prior to or in conjunction with other treatments. There is some evidence that it may be beneficial when used with radiotherapy, however, its use in conjunction with surgery is controversial (if proposed, this should be discussed with a specialist). Once the prostate treatment has been completed, the hormone treatment is usually stopped and the response observed, by following the PSA levels.

What does hormone treatment involve?

Essentially, there are two ways of reducing male hormones:

• by surgery where the testicles are removed (orchidectomy)
  
• by medication, either in the form of regular injections or tablets. Both are effective. (Refer to Table 1 and Figure 1).

Since the testicles provide over 95% of the male hormones it is obvious that their removal will reduce the levels. This occurs very quickly after the operation, which is performed sometimes as day surgery but more commonly with an overnight stay in hospital. An advantage of this form of hormone treatment is that the inconvenience and cost of regular medications is avoided.

Medications are available as an alternative to orchidectomy. The injectable drugs act on the brain to reduce the production of male hormones in the testicles and currently last from 1- 3 months per injection. This means that regular monthly or 3-monthly injections are required to control the cancer cell growth, and should these be stopped, the prostate cells will begin to grow.

Tablets are available to control the cancer cells also, although they are not frequently recommended by themselves as a first choice method of cancer control. In the past, both injectables and tablets were frequently used in combination to control prostate cancer cell growth (called total androgen ablation). However, we are currently not certain of the additional effectiveness of taking a tablet whilst on an injectable drug or in combination with orchidectomy (removal of the testicles). Sometimes hormone therapy may be given in cycles ie started and stopped repeatedly.

This type of treatment is called intermittent hormonal therapy. Typically, hormone treatment is continued for several months until PSA has reached a low level, and then discontinued. Once the PSA level in blood rises to a particular level again (and this can take many months), hormone therapy is started again. The benefits of this approach are a reduction in side effects (see the next section), and potentially prolonging the effectiveness of hormone therapy (although we are not yet sure that this is the case).

What are the current medications available in Australia?

A list of current medications available in Australia is shown in Table 1.

What are the side effects of hormone treatment?

Many of the side effects of hormone treatment are related to the lack of normal levels of male hormone within your body and occur whether you choose surgery or medications. These are summarised in table 2 below. Typically, most men suffer from poor or absent erections (impotence) and there is also a lack of interest in sexual activity (reduced libido). Your voice will not change; however, some men notice an alteration of their body hair, such that it is a different texture and may grow again on previously quite bald areas. Tiredness is a common complaint, and is related to the main male fuel being suppressed.

Hot flushes are very common in the early stages of treatment but may decline spontaneously after several months of treatment. There are medications available to reduce the intensity of this sometimes disabling symptom if required. Over many months or years there may be a decline in muscle strength and some tenderness or enlargement in the breast area.

Before commencing on hormonal therapy, it is helpful to discuss the possibility of side effects with your wife or partner. Good communication is important in dealing successfully with these changes and maintaining your close relationship.

A word about hormonal therapy

The very nature of this treatment, the removal of male hormone or its effects means that a man will experience changes in the way he feels, his attitudes, and of course his sex life. While this can be distressing, and it means communication with your partner is particularly important, it does not change who you are. It does not change your identity as a man and your ability to direct your own life. Some men feel a need for a change in focus in their lives at this stage, however, and they may take up activities which are more meaningful to them. According to these men, the years that follow can be rewarding and productive.

In information sheet no. 3 we discussed the importance of talking to those close to you, to others who may have had similar experiences and to your medical team as often as you need to. In information sheet number 4, we also suggest ways of maintaining a good quality of life. You may wish to read these additional information sheets, there is much that you can do for yourself at this stage, as there is at earlier stages.

Hormone resistance: what if the treatment stops working?

The ability of hormone treatment to control your cancer is quite variable. Some men (approximately one in five) have recurrent growth within a year from starting hormone treatment whereas others have no sign of recurrent disease after 10 years of treatment. The average time to PSA evidence of regrowth (hormone resistance) is 2.5 years. The delivery of hormone therapy in bursts (ie intermittent rather than continuous) as a way of delaying the onset of resistance is possible with medications, but not after the removal of the testicles with an operation. Whilst this approach has some theoretical advantages, its benefits have not yet been established, and continuous hormonal therapy is still regarded by most doctors as the best option.

When resistance to hormonal therapy occurs (usually indicated by rising PSA in the blood), treatment is frequently tailored to an individual’s symptoms. Symptoms typically occur many months to years after evidence of cancer regrowth and are related either to growth of the cancer in the pelvic region (blood in the urine, reduced ability to pass urine) or growth at distant sites such as the bones (pain in the pelvis, back, etc).

Treatment Options for Hormone-resistant Cancer:

Options available for this stage of the disease are:

(1) radiotherapy, to alleviate pain and control cancer growth at sites away from the prostate. Radiation is usually delivered by ‘external beam’ (meaning from outside the body) in this setting although agents which are injected are sometimes used.

(2) additional hormone treatments, typically tablets. Not many men have a lasting favourable effect from “second-line” hormonal therapy; however, a downward trend to the PSA can occur for some months. Stopping one tablet and using a different one is also sometimes helpful.

(3) steroids such as prednisolone to control pain and reduce tumour growth.

Is chemotherapy an option?

What about additional therapies?

There are additional non-medical therapies available to those with the diagnosis of prostate cancer, which we have not covered in this series. Information about these and complementary therapies is available from the cancer organisation in your state and prostate cancer support groups (see the resource list at the end of this sheet, plus Information Sheet 7). Looking after your health through improving your diet, managing stress and following an active life is a good way to begin. It is wise to advise your medical carers if you are taking additional non-conventional therapies.

Who is taking care of me?

Sometimes different types of specialists need to be involved in your care, and their different roles may not be clear. A Urologist specialises in disorders of the urinary tract and reproductive system, and so he /she will probably be the first specialist you see. If radiation therapy is an option, you will be referred to a radiation oncologist who will plan and deliver this treatment. Sometimes a medical oncologist, who specialises in the treatment of cancer, including symptom control, may also be involved.

If you are ever unsure about who has overall responsibility for your care, discuss this with your GP – our system of care can be confusing, and your GP can act as your guide as needed.

Other Resources

Mr PHIP Series - available from your state cancer organisation - ph: 13 1120.

1. Should I be tested?
2. Interpreting the PSA test
3. After the diagnosis
4. Monitoring after treatment
5. Hormonal treatment
6. Sexual function after treatment
7. Useful resources / Glossary

The prostate: a guide for men and the women who love them.
PC Walsh MD. 1997.
Warner Books, NY.
About prostate cancer and other types of prostate disease. Includes a chapter on erectile problems. This book is for those who are looking for more detail on the mechanisms of the disease and treatments with good illustrations. The author is chief Urologist in a major US Hospital.

Prostate & Cancer:
a family guide to diagnosis, treatment & survival.
Sheldon Marks MD, Fisher Books, 1997. Book.
Excellent overview of all aspects of prostate cancer and its treatment. Also includes patient information sheets.

Association of Prostate Cancer Support Groups.
This is a network of prostate cancer support groups covering all states and territories in Australia. You can find these online at:
http://www.prostatehealth.org.au.
Alternatively phone APCSG secretary Con Casey on: 02 9938 2426, or contact the cancer help-line on 13 1120.

Websites

You are not alone!
http://www.yananow.net/
This site has a strong patient input and is very supportive. It has stories from family members as well as men themselves, and has a ‘mentor’ arrangement where you can read the story of and email people who have had a particular type of treatment.

SA Support Group
http://www.merlin.net.au/~maisie
This SA website has experiences of Australian men with prostate cancer and is linked to the PSA prostate cancer support group in SA.

NT Support Group
http://www.topend.com.au/~prosper
Prosper prostate cancer support group is the only one in the Northern Territory. The site has information about the group and articles written by members.

Lions Australian Prostate Cancer Website
http://www.prostatehealth.org.au
Gives support groups, treatment centres, overseas links and other educational resources.

NCCAM: National Centre for Alternative and Complementary Medicine
http://www.nccam.nih.gov
You can search for trials of complementary treatments on PubMed from this site.

This information sheet is not intended to take the place of medical advice. Information on prostate disease is constantly being upated. We have made every effort to ensure that information was current at the time of production, however your GP or specialist may provide you with new or different information which is more appropriate to your needs.

© Repatriation General Hospital, Daw Park 2000-2004