This page describes treatments for men whose prostate cancer is no longer responding so well to their first type of hormone therapy. You might hear this stage of cancer called hormone refractory, hormone resistant, androgen independent, castration resistant, or castrate resistant prostate cancer (CRPC).

Treatments for this stage of prostate cancer are often called second-line hormone therapy, as they are given when your first hormone therapy stops working so well.

Why is my first hormone therapy not working so well?

The first type of hormone therapy you have may keep your cancer under control for several months or years. But over time, the behaviour of your cancer cells may change and your cancer could start to grow again. This can happen even though your hormone therapy is still lowering the amount of testosterone in your body.

Although your prostate cancer is no longer responding so well to your first type of hormone therapy, it could still respond to other types of hormone therapy, or a combination of other treatments.

How will I know if my first hormone therapy is not working so well?

While you're having hormone therapy you will have regular prostate specific antigen (PSA) tests to check how well the treatment is working.

A continuous rise in your PSA level may be the first sign that the hormone therapy is no longer working so well. If this happens, you might have more PSA tests to confirm this. Your doctor or nurse will also ask you about any symptoms you may have developed, such as urinary problems or bone pain. You may have scans, such as an MRI scan, a CT scan, or a bone scan. These will give your doctor a better idea of how the cancer is growing and which treatments might help.

Your doctor will talk to you about other possible treatment options if you need them. If your PSA level is only rising very slowly and you don't have any symptoms, you might not need to start a new treatment straight away. Your doctor will keep an eye on you with regular PSA tests and scans, as well as asking about your symptoms. They will talk to you about how often you should have these check-ups.

What further treatments are available?

The aim of treatment is to control your cancer and delay or manage any symptoms you might have, such as pain and urinary problems. You will probably continue with your first type of hormone therapy – even though it's stopped working so well. This is because it will still help to keep the amount of testosterone in your body low.

Further treatment options may include:

Which treatments will I have?

When your cancer stops responding to your first hormone therapy, there is no one best treatment or set order to have treatments in. The treatments you have will depend on lots of things, including what your doctor thinks will work best for you and your own thoughts – for example how you feel about the possible side effects and how a treatment will fit in with your day to day life. Talk to your doctor about what’s right for you.

You might have more than one of the treatments we describe here, while some might not be suitable for you.

When talking about possible treatments you and your doctor will consider:

  • where your cancer has spread to
  • if you have any symptoms
  • how long your cancer responded to your first hormone therapy for
  • your general health and any other health problems you have
  • the possible side effects of each treatment, as all treatments can have different side effects.

Abiraterone or enzalutamide?

If you have already had a drug called abiraterone, another drug called enzalutamide probably won't be an option. And if you’ve already had enzalutamide, abiraterone probably won’t be an option. This is because early research suggests that each drug may only have a small effect in men who've already had the other.

However, if you get severe side effects from abiraterone or enzalutamide, you may be able to try the other drug, as long as you've used the first drug for less than three months.

Speak to your doctor about which drug, if any, is the best option for you. You can also talk things through with our Specialist Nurses.


Anti-androgens, such as bicalutamide (Casodex®), are a type of hormone therapy that stop testosterone from reaching the prostate cancer cells. They may be an option if you've already had hormone therapy with injections, implants or surgery (an orchidectomy), which will have lowered the amount of testosterone in your blood.

If you're having LHRH agonist injections, you will probably start taking anti-androgens alongside them. Some health professionals call this combined androgen blockade or dual androgen blockade. It may be slightly more effective than using an LHRH agonist on its own if your PSA is rising or if your cancer has spread to other parts of the body.

If you are already having injections and anti-androgen tablets and your PSA is rising, your doctor may suggest that you stop taking the anti-androgen for a little while to see if your PSA level falls. You may hear this called a ‘withdrawal response’. Some men find that their PSA level falls for a few months, or sometimes longer.

The side effects of anti-androgens can be similar to the side effects of other types of hormone therapy and can include breast swelling and breast tenderness.

Read more about the effects of hormone therapy.


Abiraterone (Zytiga®) is a new type of hormone therapy for men with advanced prostate cancer that has stopped responding to other types of hormone therapyIt is taken as tablets and works by stopping the production of testosterone. It may help some men to live longer and can help control symptoms.

Abiraterone can be given either before or after chemotherapy, but it isn’t usually given to men who’ve already had enzalutamide.

Possible side effects of abiraterone include:

  • fluid retention, which can cause swelling in your ankles or hands
  • high blood pressure
  • liver problems
  • heart problems.

Abiraterone can also lower the level of potassium in your blood. This could make you feel tired and could cause a fast, irregular heartbeat. You will have regular blood tests and blood pressure checks, but speak to your doctor if you notice anything unusual.

You will need to take a steroid called prednisolone with abiraterone to lower the risk of side effects.

Read more about abiraterone, including the possible side effects.


Like abiraterone, enzalutamide (Xtandi®) is a new type of hormone therapy for men with advanced prostate cancer that has stopped responding to other types of hormone therapy. It is taken as tablets and works by stopping testosterone from reaching the prostate cancer cells. It may help some men to live longer and can help control symptoms.

Enzalutamide can be given either before or after chemotherapy. But it isn’t usually given to men who’ve already had abiraterone.

Possible side effects of enzalutamide include:

  • fatigue (extreme tiredness)
  • loose and watery bowel movements (diarrhoea)
  • hot flushes
  • muscle and bone pain
  • headaches
  • difficulty concentrating
  • high blood pressure
  • seizures, particularly if you have epilepsy.

Read more about enzalutamide.


Chemotherapy uses anti-cancer drugs to kill cancer cells, wherever they are in the body. 

Chemotherapy can help some men to live longer and can help to improve and delay symptoms such as pain.

In the UK, docetaxel (Taxotere®) is the most common type of chemotherapy for men with prostate cancer that has spread to other parts of the body (advanced prostate cancer) and is no longer responding so well to hormone therapy.

If you’ve already had treatment with docetaxel and your cancer has started to grow again, you might be offered a newer chemotherapy drug called cabazitaxel (Jevtana®).

You will be given steroid tablets, such as prednisolone or dexamethasone, to take with chemotherapy. This can help make the chemotherapy more effective and reduce the side effects.

Chemotherapy may not be suitable for everyone as the side effects are sometimes difficult to deal with. Side effects include being more likely to get an infection and feeling more tired than usual.

People react in different ways to chemotherapy. Some men get a lot of side effects, while others only have a few. Your doctor will check your general health to make sure you are fit enough for chemotherapy.

Read more about chemotherapy.


Steroids can stop the adrenal glands producing as much testosterone, so can help to control your cancer. They can also improve your appetite, give you more energy, and help with symptoms such as pain.

You might have steroids alone or in combination with other treatments, including chemotherapy and abiraterone. Common steroids include dexamethasone, prednisolone and hydrocortisone.

Steroids can cause side effects. But because they are given in a low dose to treat prostate cancer, most men don’t get many side effects. Before you start taking steroids, talk to your doctor or nurse about the possible side effects. They affect each man differently, and you might not get any of them.

Side effects can include:

  • indigestion and irritation of the stomach lining  take steroids after a meal and ask your doctor about medicines that could help
  • a bigger appetite – try to eat a healthy diet to keep your weight under control
  • You may have more energy and a more active mind. This can make you feel irritable, anxious or have trouble sleeping. Speak to your doctor or nurse if you’re having any problems. If you take steroid tablets twice a day, taking the second tablet early in the afternoon (before 4pm) can help with problems sleeping.
  • You may get water retention, which can cause swollen hands and feet. This is usually only a problem if you are taking steroids for a long time.
  • The risk of getting infections may be slightly higher. Tell your GP if you have any signs of infection, such as a high temperature.
  • Your skin may bruise more easily. This shouldn’t cause any problems.
  • Steroids can cause raised blood sugar levels. You may have your blood sugar level checked. Tell your doctor if you are urinating more often or get very thirsty, as these can be signs of high blood sugar.

Don’t suddenly stop taking steroids as this can make you ill.

 You will be given a steroid treatment card, which explains that you are taking steroids. You should carry this with you at all times. Show it to anyone treating you (such as a doctor, nurse or dentist), as it’s important that they know you are taking steroids.


Radium-223 (Xofigo®) is a new treatment for men with prostate cancer that has spread to the bones and has stopped responding to hormone therapy. Radium-223 can delay bone symptoms of advanced cancer, such as bone thinning, and can reduce bone pain. It may also help men live longer.

Radium-223 is a radioactive substance that is injected into a vein through a small tube inserted into your arm (a cannula). The injection only takes a few minutes.

You will normally have an injection every four weeks, for up to six injections. You can usually go home straight after each injection.

Radium-223 travels around the body in the blood and collects in bones that have been damaged by prostate cancer. It kills prostate cancer cells in the bones, but doesn’t damage many surrounding healthy cells. This means it doesn’t usually cause severe side effects. If you do get side effects, they may include:

  • feeling and being sick (nausea and vomiting)
  • diarrhoea (loose and watery bowel movements)
  • low levels of blood cells called platelets, which can cause bruising.

Read more about radium-223.


Oestrogens are a type of hormone therapy that can be used to treat prostate cancer. Oestrogen is a hormone found in both men and women, but women usually produce more.

Oestrogens are used less often than other treatments. They can be given as a tablet called diethylstilbestrol (Stilboestrol®). They can also be given through a patch that sticks to your skin like a plaster.

Like all treatments, oestrogens can cause side effects. These can be similar to the side effects of other types of hormone therapy, and can include breast swelling and tenderness. A low dose of radiotherapy to the breast area can prevent this.

Diethylstilbestrol can also increase your risk of circulation problems, such as blood clots. You will usually take drugs such as aspirin or warfarin to make this less likely. You may not be able to take diethylstilbestrol if you have a history of high blood pressure, heart disease or strokes. Your doctor or nurse will discuss this with you.

Other treatments to manage symptoms

If you have prostate cancer that has spread to the bones or other parts of the body you may get symptoms such as bone pain or urinary problems. There are treatments to help manage symptoms. These are sometimes called palliative treatments.

These treatments include:

  • pain-relieving drugs such as paracetamol or ibuprofen, or stronger drugs such as codeine or morphine
  • radiotherapy to shrink the cancer and reduce symptoms
  • drugs called bisphosphonates to treat bone problems such as pain.

Clinical trials and new treatments

A clinical trial is a type of medical research study that aims to find new and improved ways of preventing, diagnosing, treating and managing illnesses. There are clinical trials looking into new treatments for prostate cancer that is no longer responding so well to hormone therapy. There are also trials to find out whether existing treatments work better in new combinations or doses. Taking part in clinical trials can be a way of having newer treatments that aren’t yet widely available.

Read more about clinical trials or ask your doctor or nurse.


Who will be involved in my treatment?

You may see different health professionals depending on the treatment you are having. For example, you may see an oncologist as well as a urologist. Oncologists specialise in treating cancer with treatments other than surgery, such as radiotherapy and drug treatments. Urologists are surgeons who treat diseases of the urinary system, including prostate cancer.

If you have chemotherapy you may see an oncologist, as well as a specialist chemotherapy nurse, or a pharmacist. Pharmacists will check you’re having the right medicines at the right doses. You may also be offered a referral to community services. These include district nurses and palliative care nurses who can help control symptoms.

You might also have appointments and check-ups more often than before. This will depend on what treatments you are having and if you have any symptoms.

How will I know how well my treatment is working?

During and after your treatment your doctor or nurse will check how well your treatment is working.

You may have regular PSA tests, and other tests such as MRI or CT scans if your doctor thinks this is necessary. Your PSA levels alone are not always enough to know if your treatment is working. So your doctor will use your PSA level and any other test results, along with information about how you are feeling, to check how well the treatment is working. If you are feeling better this could be a sign that the treatment is working. If the treatment is not controlling the cancer then you and your doctor can discuss which treatment to try next.

One aim of your treatment will be to help manage any symptoms from your cancer, and help make sure that your daily life is as good as possible. But treatments can also cause side effects. Let your doctor or nurse know how you are feeling and about any symptoms. If you have symptoms in between your check-ups tell your doctor or nurse as soon as possible.

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Updated: June 2015 | Due for review: June 2017

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