Hormonal treatment for prostate cancer

Hormone treatment is given to patients with large tumours of the prostate and particularly those that have transgressed the capsule and in conjunction with radiotherapy, in the expectation of improving the cure chance. It is also recommended where the prostate cancer has spread/metastasised to the lymph nodes or bones.

Hormonal treatments are designed to reduce the effects of testosterone, which is the most important of all of the factors stimulating prostate cancer growth. They work by either preventing release of testosterone into the blood or blocking its actions.

It is only by understanding the complicated hormonal actions that drugs can be manufactured that can be used to treat prostate cancer.  All treatments aim to negate the effects of testosterone on the tissues and they do so in a variety of different ways.

Orchiectomy

Orchiectomy may be described as a relatively simple and straightforward procedure, but there are effective medical alternatives that require no surgical procedure. Orchiectomy is carried out either under general anaesthetic or spinal anaesthetic.  It is a relatively quick operation.  A total orchiectomy involves the removal of all testicular tissue, whereas a subtotal orchiectomy involves the removal of the hormonal and sperm producing apparatus of the testes, leaving the capsule of the testes behind.

There are two arguments in favour of orchiectomy for prostate cancer.  The first argument is that it is a procedure that is relatively quickly done.  Once performed, the procedure can be forgotten about and the patient does not have to take any medicines.

The other argument in favour of orchiectomy is that it is a “cost effective” procedure.  In fact the procedure isn’t cheap.  It is usually carried out whilst the patient is in hospital.  The £3000 cost of orchiectomy is comparable to the lifetime costs of any medical treatment for prostate cancer.

Another counter argument is that if a patient takes tablets in addition to having an orchiectomy, his survival may be prolonged:  so there remains a twice daily reminder of illness in addition to orchiectomy.

Anti-androgens

Anti-androgens are drugs that work by blocking the binding of testosterone and dihydrotestosterone to the androgen receptor.  Amongst this class of drugs are Flutamide and Bicalutamide, otherwise known as Drogenil and Casodex, and Cyproterone acetate.

Flutamide was first introduced into the treatment of prostate cancer in the 1970s.  Responses to treatment were said to be short-lived and it was noted that many patients suffered from very profound depression.  Flutamide may have some side-effects which range in severity.  The most common is diarrhoea.  This occurs in 12% of all patients.  Rarely, Flutamide may cause liver damage.  If this develops then treatment must be discontinued.  Very rarely the side-effects of Flutamide on the liver can be such that death results.

Bicalutamide was introduced into the treatment of prostate cancer in the late 1980’s.  The introduction of this drug has been important for prostate cancer patients.  It is important because it is a successful treatment without major side-effects.  It has been argued that Bicalutamide can be used as a single treatment of prostate cancer.  Bicalutamide has the advantage in that a proportion of patients will maintain potency despite therapy for prostate cancer.  Approximately 50% of all patients treated with Bicalutamide as a single agent may retain sexual potency.

Cyproterone acetate is a complicated drug in its biochemical effects upon the body.  It may cause fluid retention and its use is associated with an increased risk of strokes and heart attacks.  It may also have liver toxicity.  For this reason, it is advised that Cyproterone acetate is only used for a very short period of time and not given to patients for prolonged periods.  The Committee of Medicines do not recommend long term use of Cyproterone acetate.

Gonadotrophin releasing hormone agonists

Treatment with these drugs was initially given by intranasal spray or continuous intravenous administration.  Later subcutaneous injections were given and in the middle 1980’s these injections became available as once-monthly treatments.  Subsequently 3-monthly treatments have been developed.  The drug remains under the skin of the injection site and gradually diffuses into the blood over a period of time causing long term suppression of the male hormones.  The LHRH agonists are a humane and effective treatment of prostate cancer.

The commoner side-effects associated with treatment include hot flushes like those experienced by women around the time of menopause.  Hot flushes can be mild or severe, infrequent or very frequent.  The treatment for flushes includes other drugs, such as Clonidine and Medroxyprogesterone acetate, which themselves may cause some problems, or herbal remedies which are rarely effective.  Other side-effects include anaemia, and osteoporosis.

Recently a gonadotrophin releasing hormone antagonist has become available.

Intermittent Hormonal Therapy

In an attempt to allow the return of potency, the practice of giving medical treatment intermittently was introduced.  It is possible that this may be as effective as continuous treatment in the control of prostate cancer, but nobody is sure about this.  Potency may take 6 months or so to return after discontinuing treatment.  By this time PSA levels have started to rise and treatment needs to be restarted.  This approach may be psychologically disruptive.

Oestrogen therapy

Oestrogens have been used to treat prostate cancer for over 60 years.  The main oestrogen that is given to patients for prostate cancer is diethylstilboestrol.  This is a synthetic female hormone.  Treatment is generally given in the form of a tablet taken once or three times daily.

The effects of oestrogens on the blood are very complicated.  They include changes in the way that the blood clots and fluid retention.  As a result of this increased tendency to clot and because of fluid retention, blood pressure increases and patients taking oestrogen are more liable to strokes and heart attacks.  There is evidence that low dosages of oestrogen are just as effective as high dosages to control prostate cancer.  The side-effects are similar even if small dosages are used and has been confirmed in many studies that continue to this day.

Oestrogens have other effects too.  Approximately 30% of all patients treated with oestrogens develop quite significant gastrointestinal upset.  This consists mainly of tummy pain, wind and nausea.  There are mood changes too and all patients suffer from swelling of the breasts which may be very tender and most unpleasant.

Since there are so many alternative treatments for prostate cancer, it seems unnecessary that patients are treated nowadays with female hormones.

New drugs

Abiraterone is a very exciting new drug that almost abolishes male hormone in the patient who has either had orchiectomy or is on gonadotrophin agonist/antagonist therapy. In this situation, the body is still synthesising androgens (male hormone) via other synthetic pathways (and from precursors from the adrenal glands, albeit to a very small extent.

In conjunction with a small dose of steroid, abiraterone is effective at lowering this residual androgen in the blood and has been found to produce second endocrine (hormone) remissions in patients whose prostate cancer has become resistant to orchiectomy or gonadotrophinagonist/antagonist therapy.

Enzalutamide and caboxzantinib are also new and potentially exciting drugs for patients with advanced/metastatic prostate cancer.