Hormone Treatment: Androgen Deprivation Therapy (ADT)

In order to grow, most prostate cancers need the male hormones (androgens), the most common of which is testosterone. Most testosterone is produced in the testicles. By reducing the amount of testosterone in the man's body, the cancer will be starved and shrink.

Hormonal treatment reduces the production of testosterone by the body. It is commonly called androgen deprivation therapy (ADT). It is mainly used in the following situations:

1) When the cancer is at the advanced stage and has spread outside the prostate to other areas of the body

2) When the cancer has recurred after other treatments, or

3) It can also be used for men with curable cancers prior to radiotherapy or other treatments, which may make the treatment more effective.

Men whose tumours have already spread by the time they are first diagnosed with prostate cancer will often not undergo such treatment as surgery or radiation. Instead, their treatment journey will start with primary Hormone treatment, which initially should lower the PSA level considerably and stop the cancer progressing. Regular PSA readings are again adopted in order to monitor the cancer and make sure the treatment is effective.

If the ‘first-line’ hormone drugs lose their effectiveness, there are other, newer drugs which have been shown to work on many patients. These ‘second-line’ drugs are often used in combination with the first-line hormone drugs. You may find the treatment path diagram further down this page helpful. These drugs have different mechanisms of action and side effects.

Hormone treatment alone does not cure the cancer but may control it for anything from 2 to 10+ years. A marked lowering of the PSA is usually a good indication of the effectiveness of hormone treatment.

There are two main types of hormone treatment: LHRH analogues and anti-androgens.

LHRH analogues

This is short for Luteinising Hormone-Releasing Hormone. These drugs can decrease the amount of testosterone produced by the testicles as effectively as surgical removal. Two common examples of these drugs are Zoladex (goserelin®) administered by the injection of a slowly dissolving pellet either monthly or three-monthly. The other is Prostap (leuprorelin®) administered in liquid form.

Less common is Decapeptyl or Gonapeptyl (triptorelin®). This is another drug that can be used, especially in cases of aggressive advanced prostate cancer. This is administered in one-, three- or six-monthly injections.

When first administered, all of these drugs cause an initial surge of testosterone, which is counteracted by a short course of anti-androgen tablets shortly before and after the first injection.

Degarelix (Firmagon®) works in a slightly different way to LHRH analogues but has been shown to be just as safe and effective. The advantage of this drug (as opposed to others listed above) is that there is no tumour flare and thus no need for an anti-androgen before an LHRH analogue treatment. It is approved by NICE for cases of advanced prostate cancer where it has spread to the spinal column. It is administered by injection under the skin.

Anti-androgens

These drugs do not stop the production of testosterone but block the effects of androgens produced by the testicles and adrenal glands. Two common examples of these drugs are Cyprostat (cyproterone acetate®) and Casodex (bicalutamide®).

They are usually taken in pill form, which makes them attractive to those who do not like the thought of regular injections. Anti-androgens can be used as a stand-alone therapy (referred to as ‘anti-androgen monotherapy’), or can be used in combination with LHRH analogues, referred to as ‘combined androgen blockade’. Some men may prefer anti-androgens because of the reduced side effects, but evidence shows that they are not quite as effective as LHRH analogues.

Intermittent Hormone treatment

Intermittent Hormone treatment is a process in which the hormone treatment is started and stopped for periods while monitoring the PSA. When the PSA rises, treatment is restarted. The aim is to reduce the side effects of the treatment. Some trials have shown that intermittent treatment can be as effective as continuous treatment, and with fewer side effects.

Side effects of hormone treatments

A common side effect, particularly of LHRH analogues, is hot flushes for short periods, which can occur at night, affecting sleep, for which a short course of low-dose anti-androgens may be prescribed. Eliminating alcohol, tea and coffee (or using decaffeinated drinks) and going on a soya diet (to replace milk) may also help. Weight gain, bone or muscle pain, joint pain, numbness and tingling in hands and feet, and possible hair loss on face, arms, legs or underarm are other listed side effects. Some may find these hard to live with, but with time many will reduce in severity as the body adjusts. Medication can, of course, be changed should these become a problem.

LHRH analogue side effects The main side effect is that the patient will become impotent and lose his sex drive; but unlike orchidectomy (surgical removal of the testicles) the process gradually reverses if the patient stops taking the drug. Some men may suffer from decreased size of testicles and some slight penile shrinkage. Initially these drugs can produce a flare in testosterone, which settles after a few weeks.

Anti-androgen side effects A common side effect of these drugs is tender or enlarged breast tissue (gynaecomastia), which may subside if treatment is ceased. Low doses of Tamoxifen (an anti-oestrogen) can reduce this side effect. Other possible concerns may be nausea, diarrhoea, itching, feeling weak, and problems with the liver. As the drugs affect your hormone levels, this may cause some anxiety or depression. Although there is still a risk of impotence and other adverse sexual side effects with anti-androgens, these are less severe than with LHRH analogues (or with orchidectomy, where it is permanent).


The STAMPEDE trial has shown that some men with high-risk cancer can benefit from a combination of chemotherapy and Hormone treatment. After completion of chemotherapy, Hormone treatment with drugs such as Zoladex or Prostap will continue, either continuously or intermittently, However, the cancer will eventually no longer respond to the hormone drugs. This is called hormone relapsed prostate cancer (still sometimes referred to by the medical profession as ‘castration resistant’ or ‘hormone resistant’ prostate cancer). A rise in PSA level is the first sign of the treatment becoming ineffective. When this happens, there are several second-line treatments, described later in this section. At this stage an anti-androgen such as Casodex may be used. The steroid dexamethasone could follow, which can be used in conjunction with Radium-223. As steroids are only effective for a limited amount of time, newer drugs are now being used.

Abiraterone Acetate (Zytiga®)
This has helped many patients with advanced cancers that have become resistant to hormone treatments. Abiraterone is currently authorised for use in the NHS as a treatment before or after chemotherapy. It is highly effective in improving survival of some types of prostate cancer, but not all, so it doesn’t work for every patient. Some men have to be taken off the drug if an adverse reaction in the liver occurs.

Enzalutamide (Xtandi®)
This is an advanced anti-androgen that is showing outstanding results, similar to abiraterone. It is approved by NICE before or after chemotherapy. However, it cannot currently be given after abiraterone, unless abiraterone has caused toxicity problems within the first three months of it being started. Both these drugs are generally well tolerated. Tiredness is the most common side effect associated with them.

Steroids
Steroids have been in use for many years and have proved to be effective, though only for a limited period of time.These include dexamethasone and prednisolone. These drugs stop the adrenal glands from producing other male hormones. A recent trial has shown dexamethasone to be twice as effective as prednisolone; so dexamethasone should now be considered the preferred option. The main side effect of steroids is an increased appetite.


Radium-
223 (Xofigo®)
Formerly known as Alpharadin, Radium-223 is proving an excellent treatment for bone metastases associated with advanced prostate cancer. This is a much safer treatment, as it only targets the cancerous areas on the bones. It is very similar to calcium and, when injected into the bloodstream, is rapidly taken up in the bone. It is not taken up by lymph nodes and visceral metastases (such as liver or lung). It emits very high-energy alpha particles that cause lethal damage to adjacent tumour cells and has undergone a trial with nearly 1,000 patients with hormone relapsed prostate cancer. The results show that Radium-223 improves survival by a similar length of time as abiraterone or enzalutamide and is now a standard treatment for men with hormone resistant prostate cancer and bone metastases. It has been approved by NICE.

PSMA
Prostate-Specific Membrane Antigen (PSMA) radiotherapy – dubbed a ‘search and destroy’ method of treatment is based on imaging techniques which light up tumours, in order to plan future treatment. This new technique simultaneously delivers a radioactive payload, which experts described as delivering ‘a bullet instead of a light’. It uses radioactive isotope, which binds to a protein on the surface of malignant cells, attacking them without damaging surrounding tissues.


Suggested treatment path

For those with advanced prostate cancer.
It may not be applicable to every man, so
it is always important to follow the advice
of your medical professional.

The programme is only a guide and is
flexible and can continue over many
years. New treatments are being
developed in many different countries.
Keep optimistic. New second-generation
drugs to abiraterone and enzalutamide
are currently being trialled, these are
Darolutamide and Apalutamide.

 


Zoladex + Docetaxel

(LHRH analogue) + (Chemotherapy)

Casodex (bicalutamide)

Dexamethosone + Radium-223

Abiraterone or Enzalutamide
Darolutamide or Apalutamide

Docetaxel/Cabazitaxel

 

 

Spread of Prostate Cancer

In time, prostate cancer cells may invade local tissues, or break away and spread to other areas of the body via the bloodstream or lymphatic system.

When these cells reach a new site they may form a new cancer, called a secondary tumour or metastasis. The areas most commonly affected are the lymph nodes, bones and lungs.