Personalised Medicine at a Glance: Prostate Cancer
For patients, policy makers and other non-medical professionals
This text was prepared by ESMO for the European Alliance for Personalised Medicine in March 2015 and updated in February 2017
Cancer of the prostate is the most common cancer in men. Each year, approaching 420,000 European men are diagnosed with it. But, even though so many prostate cancers are diagnosed, the number of deaths each year from the disease is fewer than 100,000. This is partly because of success in treatment, but also because some prostate cancers grow only very slowly.
Assessing whether prostate cancer in a particular man will or will not threaten his life – and matching treatment to risk – is an exceedingly difficult balance. No-one wants to miss out on a treatment that can achieve cure. But effective treatments may cause impotence and incontinence; and no-one wants to risk these side-effects either, unless the treatment is absolutely necessary. Achieving the goal of appropriate, individualised prostate cancer therapy is still some way off, but we are making significant progress.
“Prostate problems” such as difficulty in urination and increased frequency become more common with age and are often caused by non-cancerous enlargement of the gland. The presence of a cancer is suggested either by the abnormal feel of the prostate on rectal examination, or by a raised level in the blood of a substance produced by prostate cells called prostate-specific antigen (PSA). But neither rectal examination nor PSA is conclusive.
To diagnose a cancer requires biopsy: a fine hollow needle is used repeatedly to take tissue samples from the prostate and these are then examined in a pathology lab. Looking at the biopsied tissue under a microscope reveals whether the gland contains a tumour, and how large it is. Doctors then assign a Gleason grade to the cancer cells they have extracted, based on the extent to which their appearance differs from normal. The more abnormal the cells, the higher the Gleason score and the more likely the tumour is to grow and spread.
Localised disease: tailoring treatment to risk
If the tumour is small and of low Gleason grade, doctors may suggest active surveillance. Regular PSA tests and biopsies every year or two are used to detect whether the tumour is becoming more aggressive. Recently, researchers have established the value of magnetic resonance imaging (MRI) as a way of detecting abnormalities in the prostate. It is now seen as a useful guide to the frequency and targeting of tissue biopsies.
But if a tumour is high grade or large, or if it threatens to spread beyond the prostate, active treatment will be recommended. This can take the form either of surgical removal of the gland (radical prostatectomy) or radiotherapy, delivered by external beam radiation or by implantation of radioactive seeds (brachytherapy). The aim of such treatment is cure, though in some men the cancer will recur (see below).
With tumours of certain size and location in the prostate, there may also be the possibility of destroying abnormal tissue using new techniques such as high intensity focused ultrasound.
Even though the disease has not spread, there may be a case for accompanying local treatment with hormone (androgen deprivation) therapy (described below).
Overall, recent years have seen a shift away from radical treatment of localised, low- and intermediate-risk prostate cancer towards a more conservative approach, whenever this does not appreciably reduce the prospects of surviving the cancer. The choice between active surveillance and various treatment options will be heavily influenced by the preferences of the patient.
If prostate cancer shows signs of recurrence after prostatectomy (with, for example, a rising level of PSA), it is likely that radiotherapy will be recommended. If the disease recurs in a man who has had radiotherapy rather than surgery, the likely recommendation is androgen deprivation therapy.
Advanced disease: need for systemic treatment
Patients generally need systemic treatment if the cancer has spread to local tissues around the prostate or to distant sites in the body. The mainstay of initial treatment is hormonal therapy. Prostate cells grow in response to the androgenic hormone testosterone, and the essence of hormone treatment is to deprive prostate cells of this growth stimulus. So hormone therapy for prostate cancer is also called androgen deprivation therapy.
One approach is to reduce production of testosterone by the testes and adrenal glands. A complementary strategy is to block the effects of testosterone on cancer cells.
Reductions in testosterone production can be achieved by injections of LHRH agonists (monthly or three-monthly), while daily administration of tablets targets the androgen receptor through which testosterone produces its effects on prostate cells.
There has been some recent success using a new drug called abiraterone, which very effectively stops the body producing testosterone when LHRH agonists are no longer able to suppress cancer growth. Abiraterone or another drug called enzalutamide can be used in men without symptoms or with only mild symptoms, and for men with cancer that no longer responds to hormone (androgen deprivation) therapy.
An unfortunate feature of prostate cancer is that it often produces secondary tumours in bone. Patients who develop painful bone metastases can obtain relief through conventional radiotherapy or through the injection of a radioactive agent (radium-223) that concentrates in abnormal bone and kills the cancer cells growing there.
Chemotherapy with cytotoxic drugs such as docetaxel is also an option for metastatic prostate cancer that no longer responds to hormonal treatment, though patients may find the side effects difficult to tolerate.
In several cancers, such as those of the breast, lung and colon and in melanoma, researchers have identified genetic mutations that drive the uncontrolled growth of tumour in at least a proportion of patients. And this has encouraged the development of drugs that successfully target these specific abnormalities.
The androgen receptor is a key protein in prostate cancer progression and a focus of intense research. However, we are still looking for genetic markers that reliably predict the efficacy of particular drugs. In this respect, personalised medicine in prostate cancer is lagging behind that in other areas. On the other hand, we do have a range of effective treatments – some involving drugs, but also sugery and various forms of radiotherapy and other local treatments – and we have increasingly precise strategies for matching how aggressively we treat the tumour to how aggressive the tumour is likely to be in an individual patient.