Treatments For Advanced Prostate Cancer
Definitions and overview
Advanced prostate cancer means your disease has spread out of the prostate through the lymph nodes and into other parts of your body.
Locally advanced prostate cancer means cancer has spread to the area immediately outside. It may have spread to the seminal vesicles, the lymph nodes in the pelvis or the neck of the bladder.
Advanced prostate cancer is the description for cancer has spread (or metastasized) into the soft tissues and bones of your body. This means your cancer cannot be cleared or cured, but the options and life expectancy for men with advanced prostate cancer has been transformed very significantly in recent years.
Improvements in life expectancy
A decade ago, a man with metastatic prostate cancer would typically have a life expectancy of two to three years. Today, life expectancy for men with the same advanced disease is likely to be five to six years. In the UK the survival rate for men with stage 4 prostate cancer is approximately 50%, meaning that 50 out of every 100 men will survive their cancer for 5 years or more after they are diagnosed with stage 4 prostate cancer*. There is now a much broader range of chemotherapy drugs available for men with advanced disease with greater efficacy (effectiveness). We also have better treatments to control the symptoms of advanced prostate cancer, such as pain from metastases. In this section, we consider in more detail the different treatments that are available and evidence for their effectiveness.
First line treatment for advanced prostate cancer
The established first line approach is to control the progression of the disease by reducing levels of testosterone in the body. This is because testosterone increases the speed at which prostate cancer cells reproduce.
There are two different ways to lower testosterone levels. Hormone therapy lowers the levels of testosterone in the body by taking tablets or having injections. It is sometimes referred to as “medical castration”. The surgical option involves removing the testicles, known as “surgical castration” or orchidectomy, although this is now rarely used.
Another approach is called anti-androgen treatment. Androgens (including testosterone) have to bind to a protein in the cell called an androgen receptor to work. Anti-androgens are drugs that bind to these receptors so the androgens can’t, effectively blocking them. The main side-effects are gynaecomastia “breast enlargement” and breast pain, although a single radiotherapy dose to the breasts can help this side-effect.
Combining anti-androgens with testosterone reduction is known as Maximum Androgen Blockade (or MAB) and may be used if hormone treatment alone is not working sufficiently.
Recently, a landmark study has called into question the approach of starting with hormone therapy and only introducing chemotherapy one hormone deprivation ceases to have an effect (known as castrate resistant or castrate refractory prostate cancer). The trial, E3805, involved 790 men between July 2006 and November 2012, who were randomly assigned to anti-androgen treatment (ADT) plus six cycles of the chemotherapy drug Docetaxel or ADT alone.
Treating with chemotherapy at the same time as the start of hormone deprivation was found to increase survival by 13 months in all patients and 17 months in men with high-volume disease.
“This is an unprecedented improvement in survival,” comments Dr Ahmed El-Modir, Birmingham Prostate Clinic oncologist. “Normally, an improvement in survival of two or three months is considered significant, but 17 months is groundbreaking.
“What it tells us is that particularly for men with high volume disease, there is a real benefit in ‘hitting hard’ early on with treatment, rather than taking the traditional stepped approach of hormone therapy then chemotherapy.”
Castrate refractory prostate cancer: a wider range of options
In this section, we explain the treatments available at Birmingham Prostate Clinic for patients once their disease becomes resistant to hormone treatment, called castrate refractory prostate cancer. Two types of treatments are needed to:
- Control the cancer and prevent further spread of cancer
- Control or prevent the symptoms caused by the spread of prostate cancer to the bones
Treatments to control and prevent further cancer spread in patients with castrate refractory advanced prostate cancer:
At BPC we offer:
- Hormones (LHRH-analogues, GnRH-antagonists, Anti-androgens, Abiraterone acetate (Zytiga), Enzalutamide (Xtandi), Diethylstilboestrol)
- Chemotherapy (Docetaxel, Cabazitaxel, Mitoxantrone).
- Radium-223 (Xofigo)
Other treatment options ongoing clinical studies:
- Autologous cellular immunotherapy, which is in late trial stage and although not currently available outside a trial setting in the UK, is likely to be licensed soon.
Treatments to control and prevent symptoms caused by the spread of prostate cancer to the bones
Palliative External beam radiotherapy
Radiopharmaceuticals: Strontium-89 (Metastron), samarium-153
Radium-223 dichloride is now licensed and called Xofigo. This is not widely available in the UK but BPC is one of a relatively small number of specialist centres using this treatment.
Zolidronic acid (Zometa) is a bisphosphonate given by a 15-minute intravenous infusion every 3–4 weeks. It reduces the risk of bone complications, including pain and fractures.
Xgeva (Denosumab): this is a newly licensed drug available at BPC.
Surgery may be undertaken to treat bone fractures or to relieve the pressure on the spinal cord by bone metastases.
“Patients can experience pain, anaemia and fatigue and you really need a multi-modality treatment to meet the individual needs of each patient.”