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 treatments, 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 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 the hormone therapy is still lowering your testosterone levels.
Although your prostate cancer is no longer responding so well to your first hormone therapy, it may respond well to other types of hormone therapy or a combination of 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 hormone therapy 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. You will probably continue with your first type of hormone therapy – even though it's not 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:
- other treatments to manage symptoms
- clinical trials and new treatments
Which treatments will I have?
When your cancer stops responding to your first hormone therapy, there is no best treatment or best order to have treatments in. You might have more than one treatment, while some treatments might not be suitable for you.
The treatments you have will depend on lots of things. 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
- what your doctor thinks will work best for you
- your own thoughts and feelings – for example, how you feel about the possible side effects and how a treatment would fit in with your daily life.
Abiraterone or enzalutamide?
If you've 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 either abiraterone or enzalutamide, you may be able to try the other one, 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 level is rising, or if your cancer has spread to other parts of the body (advanced prostate cancer).
If you are already having injections and anti-androgen tablets and your PSA level 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.
Abiraterone (Zytiga®) 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 the production of testosterone. It may help some men to live longer and can help control symptoms.
Abiraterone can cause side effects. You'll need to take a steroid called prednisolone with abiraterone to lower the risk of 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 of advanced prostate cancer.
Chemotherapy uses anti-cancer drugs to kill cancer cells, wherever they are in the body. It can help some men to live longer, and improve and delay symptoms such as pain.
If you’ve already had 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 treatment more effective and reduce the side effects of chemotherapy.
Chemotherapy isn't suitable for everyone as the side effects can be difficult to deal with. 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're fit enough for 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.
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
- having more energy and a more active mind, which could make you feel irritable or anxious or give you trouble sleeping – take steroids before 4pm and tell your doctor or nurse if this is a problem
- water retention, which can cause swollen hands and feet
- a slightly higher risk of getting infections – tell your GP if you have a high temperature or other signs of infection
- bruising more easily
- raised blood sugar levels – tell your doctor if you need to urinate (pee) more often or get very thirsty, as these can be signs of high blood sugar
- weak bones – you might need to take medicines or calcium and vitamin D supplements.
Don’t suddenly stop taking steroids as this can make you ill.
You'll be given a steroid treatment card that says you're taking steroids. You should carry this with you at all times and show it to anyone treating you (such as a doctor, nurse or dentist). It’s important that they know you're 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. It is a type of internal radiotherapy called a radioisotope. Radium-223 helps some men to live longer. It can also delay some symptoms, such as bone fractures, and can help to reduce bone pain. It can be given either before or after chemotherapy.
Radium-223 is injected into a vein in your arm. You will normally have an injection every four weeks, for up to six injections. Each injection only takes a few minutes and you will be able to go home straight away after each one.
Radium-223 travels around the body in the blood and is drawn towards the parts of the bones that have been damaged by the cancer. It collects in these parts of the bones and kills the cancer cells, but doesn’t damage many healthy cells. This means that any side effects of radium-223 tend to be mild.
Oestrogens are a type of hormone therapy that can be used to treat prostate cancer that's no longer responding to other types of hormone therapy. They aren't used very often and may not be suitable if you have other health problems. Oestrogen is a hormone that's naturally found in both men and women, but women usually produce more.
Oestrogens can be given as a tablet called diethylstilbestrol (Stilboestrol®) or through a patch that sticks to your skin like a plaster.
The side effects can be similar to the side effects of other types of hormone therapy.
Other treatments to manage symptoms
If your prostate cancer has spread to the bones or other parts of your 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. They include:
Clinical trials and new treatments
A clinical trial is a type of medical research that aims to find new and improved ways of preventing, diagnosing, treating and managing illnesses. There are clinical trials looking at new treatments for prostate cancer and new ways of using existing treatments, as well as the best order to have treatments in. If you decide to take part in a clinical trial, you may be able to have a newer treatment that isn't yet widely available.
Read more about clinical trials or speak to your doctor or nurse.
Who will be involved in my treatment?
You may see different health professionals depending on the treatment you have. For example, if you have chemotherapy you may see an oncologist, a specialist chemotherapy nurse, or a pharmacist, who will check you're having the right medicines at the right doses.
You may be offered a referral to community services, such as district nurses and palliative care nurses who can help control symptoms. You might also have appointments more often than before to help manage symptoms or to give you your treatment.
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 scans or CT scans. Your PSA levels alone aren't 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're 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 isn't 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, so that your daily life is as good as possible. But treatments can cause side effects. Let your doctor or nurse know how you are feeling and about any symptoms or side effects. If you have symptoms in between check-ups, tell your doctor or nurse as soon as possible.
Updated: August 2017 | Due for review: August 2019
- Bahl A, Oudard S, Tombal B, Ozguroglu M, Hansen S, Kocak I, et al. Impact of cabazitaxel on 2-year survival and palliation of tumour-related pain in men with metastatic castration-resistant prostate cancer treated in the TROPIC trial. Ann Oncol. 2013 May 30;24(9):2402–8.
- Bosset P-O, Albiges L, Seisen T, de la Motte Rouge T, Phé V, Bitker M-O, et al. Current role of diethylstilbestrol in the management of advanced prostate cancer. BJU Int. 2012 Dec;110(11 Pt C):E826-829.
- Cao Y, Ma J. Body Mass Index, Prostate Cancer-Specific Mortality, and Biochemical Recurrence: a Systematic Review and Meta-analysis. Cancer Prev Res (Phila Pa). 2011 Jan 13;4(4):486–501.
- Collins R, Trowman R, Norman G, Light K, Birtle A, Fenwick E, et al. A systematic review of the effectiveness of docetaxel and mitoxantrone for the treatment of metastatic hormone-refractory prostate cancer. Br J Cancer. 2006 Aug 1;95(4):457–62.
- Davies NJ, Batehup L, Thomas R. The role of diet and physical activity in breast, colorectal, and prostate cancer survivorship: a review of the literature. Br J Cancer. 2011 Nov 8;105:S52–73.
- De Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364(21):1995–2005.
- Dorff TB, Crawford ED. Management and challenges of corticosteroid therapy in men with metastatic castrate-resistant prostate cancer. Ann Oncol. 2013 Jan 1;24(1):31–8.
- Gardner JR, Livingston PM, Fraser SF. Effects of Exercise on Treatment-Related Adverse Effects for Patients With Prostate Cancer Receiving Androgen-Deprivation Therapy: A Systematic Review. J Clin Oncol. 2014 Feb 1;32(4):335–46.
- Hechtman LM. Clinical Naturopathic Medicine [Internet]. Harcourt Publishers Group (Australia); 2014 [cited 2015 Jul 21]. 1610 p. Available from: http://www.bookdepository.com/Clinical-Naturopathic-Medicine-Leah-Hechtman/9780729541923
- Husson O, Mols F, Poll-Franse LV van de. The relation between information provision and health-related quality of life, anxiety and depression among cancer survivors: a systematic review. Ann Oncol. 2010 Sep 24;mdq413.
- Isbarn H, Pinthus JH, Marks LS, Montorsi F, Morales A, Morgentaler A, et al. Testosterone and Prostate Cancer: Revisiting Old Paradigms. Eur Urol. 2009 Jul;56(1):48–56.
- Keogh JWL, MacLeod RD. Body Composition, Physical Fitness, Functional Performance, Quality of Life, and Fatigue Benefits of Exercise for Prostate Cancer Patients: A Systematic Review. J Pain Symptom Manage. 2012 Jan;43(1):96–110.
- Larkin D, Lopez V, Aromataris E. Managing cancer-related fatigue in men with prostate cancer: A systematic review of non-pharmacological interventions: Managing prostate cancer fatigue. Int J Nurs Pract. 2014 Oct;20(5):549–60.
- Matsuoka T, Kawai K, Kimura T, Kojima T, Onozawa M, Miyazaki J, et al. Long-term outcomes of combined androgen blockade therapy in stage IV prostate cancer. J Cancer Res Clin Oncol. 2015 Apr;141(4):759–65.
- Mishra SI, Scherer RW, Geigle PM, Berlanstein DR, Topaloglu O, Gotay CC, et al. Exercise interventions on health-related quality of life for cancer survivors. Cochrane Database Syst Rev. 2012;8:CD007566.
- Mottet N, Bellmunt J, Briers E, Bolla M, Bourke L, Cornford P, et al. EAU-ESTRO-ESUR-SIOG Guidelines on prostate cancer. European Association of Urology; 2017.
- National Institute for Health and Care Excellence. Abiraterone for treating metastatic hormone-relapsed prostate cancer before chemotherapy is indicated. Technology appraisal guidance 387. 2016.
- National Institute for Health and Care Excellence. Cabazitaxel for hormone-relapsed metastatic prostate cancer treated with docetaxel (Final Appraisal Determination). 2016.
- National Institute for Health and Care Excellence. Degarelix for treating advanced hormone-dependent prostate cancer. Technology appraisal guidance 404 [Internet]. 2016.
- National Institute for Health and Care Excellence. Enzalutamide for metastatic hormone-relapsed prostate cancer previously treated with a docetaxel-containing regimen. Technology appraisal guidance 316. 2014.
- National Institute for Health and Care Excellence. Enzalutamide for treating metastatic hormone-relapsed prostate cancer before chemotherapy is indicated. Technology appraisal guidance 377. 2016.
- National Institute for Health and Care Excellence. Prostate Cancer: diagnosis and treatment. Full guideline 175. 2014.
- National Institute for Health and Care Excellence. Radium-223 dichloride for treating hormone-relapsed prostate cancer with bone metastases. Technology appraisal guidance 412. 2016
- National Institute for Health and Clinical Excellence. Abiraterone for castration-resistant metastatic prostate cancer previously treated with a docetaxel-containing regimen. NICE technology appraisal guidance 259. 2012.
- National Institute for Health and Clinical Excellence. Docetaxel for the treatment of hormone-refractory metastatic prostate cancer. NICE technology appraisal guidance 101. 2006.
- Ndibe C, Wang CG, Sonpavde G. Corticosteroids in the Management of Prostate Cancer: A Critical Review. Curr Treat Options Oncol [Internet]. 2015 Feb [cited 2017 Feb 1];16(2)
- Noonan KL, North S, Bitting RL, Armstrong AJ, Ellard SL, Chi KN. Clinical activity of abiraterone acetate in patients with metastatic castration-resistant prostate cancer progressing after enzalutamide. Ann Oncol. 2013 Jul 1;24(7):1802–7.
- Parker C, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, Fosså SD, et al. Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer. N Engl J Med. 2013;369(3):213–23.
- Richman EL, Kenfield SA, Stampfer MJ, Paciorek A, Carroll PR, Chan JM. Physical Activity after Diagnosis and Risk of Prostate Cancer Progression: Data from the Cancer of the Prostate Strategic Urologic Research Endeavor. Cancer Res. 2011 May 24;71(11):3889–95.
- Roviello G, Cappelletti MR, Zanotti L, Gobbi A, Senti C, Bottini A, et al. Targeting the androgenic pathway in elderly patients with castration-resistant prostate cancer: A meta-analysis of randomized trials. Medicine (Baltimore). 2016 Oct;95(43):e4636.
- Scher HI, Fizazi K, Saad F, Taplin M-E, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012 Sep 27;367(13):1187–97.
- Schmitt B, Bennett C, Seidenfeld J, Samson D, Wilt T. Maximal androgen blockade for advanced prostate cancer. Cochrane Database Syst Rev. 1999;2.
- Scottish Medicines Consortium. Abiraterone acetate 250mg tablets (Zytiga®) SMC No. (764/12) [Internet]. 2012.
- Scottish Medicines Consortium. Abiraterone acetate 250mg tablets (Zytiga®) SMC No. (873/13) [Internet]. 2015.
- Scottish Medicines Consortium. Cabazitaxel 60mg concentrate and solvent for solution for infusion (Jevtana®) SMC No. (735/11) [Internet]. 2016.
- Scottish Medicines Consortium. Enzalutamide 40mg soft capsules (Xtandi®) SMC No. (1066/15) [Internet]. 2016.
- Scottish Medicines Consortium. Enzalutamide 40mg soft capsules (Xtandi®) SMC No. (911/13) [Internet]. 2013.
- Scottish Medicines Consortium. Radium-223 dichloride for the treatment of adults with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastases. 2015.
- Serpa Neto A, Tobias-Machado M, Kaliks R, Wroclawski ML, Pompeo ACL, Del Giglio A. Ten Years of Docetaxel-Based Therapies in Prostate Adenocarcinoma: A Systematic Review and Meta-Analysis of 2244 Patients in 12 Randomized Clinical Trials. Clin Genitourin Cancer. 2011 Dec;9(2):115–23.
- Simmons MN, Klein EA. Combined Androgen Blockade Revisited: Emerging Options for the Treatment of Castration-Resistant Prostate Cancer. Urology. 2009 Apr;73(4):697–705.
- Sternberg CN, Bono JS de, Chi KN, Fizazi K, Mulders P, Cerbone L, et al. Improved outcomes in elderly patients with metastatic castration-resistant prostate cancer treated with the androgen receptor inhibitor enzalutamide: results from the phase III AFFIRM trial. Ann Oncol. 2014 Feb 1;25(2):429–34.
- Teply BA, Luber B, Denmeade SR, Antonarakis ES. The influence of prednisone on the efficacy of docetaxel in men with metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis. 2016;19(1):72–78.
- Tillisch K. Complementary and alternative medicine for functional gastrointestinal disorders. Gut. 2006 May 1;55(5):593–6.
- Trottier G, Boström PJ, Lawrentschuk N, Fleshner NE. Nutraceuticals and prostate cancer prevention: a current review. Nat Rev Urol. 2009 Dec 8;7(1):21–30.
- World Cancer Research Fund International. Continuous Update Project report: Diet, Nutrition, Physical Activity and Prostate Cancer [Internet]. 2014.
- Zhang W, Wu T-Y, Chen Q, Shi X-L, Xiao G-A, Zhao L, et al. Indirect comparison between abiraterone acetate and enzalutamide for the treatment of metastatic castration-resistant prostate cancer: a systematic review. Asian J Androl [Internet]. 2016
The following people helped to review this information:
- Vanessa Basketter, Urology Lead Nurse, University Hospital Southampton NHS Foundation Trust
- Chris Parker, Consultant Clinical Oncologist, The Royal Marsden NHS Foundation Trust, Sutton
- Deborah Victor, Uro-oncology Clinical Nurse Specialist, Royal Cornwall Hospitals NHS Trust
- Linda Welsh, Prostate Specialist Radiographer and Clinical Research
Radiographer, Torbay Hospital
- Our Specialist Nurses
- Our Volunteers.