Prostate Cancer
Prostate cancer constitutes a major health problem. In many developed countries it is the most commonly diagnosed cancer in men. It is estimated that the lifetime risk of western men having prostate cancer is about 30%, with the risk of dying from the cancer being 3%. However, not every prostate cancer possesses a threat to the life of the individual and indeed does not warrant treatment. Thus many men die with prostate rather than die from prostate cancer.
What is it?
BPH is a gradually progressive disease that commences in men who are around 40 years of age. It's prevalence increases with age. 40% of men over 60 have lower urinary tract symptoms (LUTS), about half of whom have an impaired quality of life, owing to BPH. The cause is unknown. There is a non-malignant growth (usually of the transition zone) of the prostate. This process reduces the distensibility of the urethra when passing urine.
What are the risk factors?
Age is the single greatest risk factor for prostate cancer. The greater your age the more risk you have for prostate cancer. A family history also increases your risk, especially if one or more first-degree relatives are affected with an early age of onset. Another risk factor is saturated fats, for example, cheese, eggs and red meat. It is thought that free radicals produced during fat metabolism damage prostate cells. Race is another important risk factor, with the disease being more common in Afro-Caribbean populations and less in men of Asian origin.
Are there preventative measures?
Nothing will guarantee 100% protection from prostate cancer. Sunlight has shown a protective effect. The prostate cancer risk rises in relation to distance from the sun. Also, dietary supplements such as vitamin E and selenium may reduce the risk. Furthermore decreasing the amount of saturated fats and increasing the intake of some vegetables, such as tomatoes, which contain lycopenes, help through reducing the oxidative stress (from free radicals) on prostatic cells.
What are the symptoms?
Men with prostate cancer can present with a variety of different symptoms, and often with no symptoms at all.
The presenting symptoms can be broadly divided into:
(e.g. blood in the urine, compression of the pipe from the kidney to the bladder causing loin pain)
How is it diagnosed?
Traditionally, prostate cancer has been diagnosed on the basis of symptoms that develop, either as a result of local infiltration of the prostate or adjacent structures, or symptoms that develop from metastases. Nowadays men are taking more of an active participation in their health. This has led men to ask for specific tests in order to "screen" themselves for prostate cancer. It is quite common for prostate cancer to be diagnosed without any particular symptoms.
Anyone with suspected prostate cancer should have three specific tests done. These are:
PSA
The PSA, or Prostate Specific Antigen, is a protein exclusively secreted by the glandular lining of the prostate. Its function is to liquefy the semen after ejaculation. Normally only a tiny proportion is absorbed into the bloodstream (less than one millionth). In prostate cancer there is disruption of the membrane surrounding the glands by the cancer cells. This causes PSA to leak into nearby blood vessels more than it would normally. This obviously causes an increase in the PSA found in blood. In a healthy male with no prostate symptoms the PSA is usually accepted to below 4 ng/ml but this rises with age so that in men over 70 a cut-off of 6.5 ng/ml is accepted. The PSA can also rise in BPH and a way to help discriminate between the two is compare the 'free' PSA to the 'total' PSA.
When PSA is present in the bloodstream most of it is bound to a protein, however some of it unbound or 'free'. For unknown reasons, in prostate cancer, the amount of 'free' PSA is reduced. Using this value and creating a ratio of free-to-total PSA in the blood, doctors can predict whether a total PSA result is likely to be cancer or BPH. A ratio of 0.18 or less can suggest that cancer is present, but does not categorically confirm it.
Digital Rectal Examination
This is the most useful clinical method for doctors to assess the prostate. A finger is passed into the anus and the prostate is felt through the wall of the rectum. The doctor is able to feel the size and the consistency of the prostate. Some cancers will be palpable as firm nodules.
Trans-Rectal Ultrasound and Biopsy
If the DRE is suspicious and the PSA is high then the doctor will organise a trans-rectal ultrasound (TRUS) and a biopsy. This involves having an ultrasound probe inserted into the rectum. The prostate is then able to be visualised on screen. Under direct guidance biopsies are taken using a type of needle. Between 6 and 12 biopsies are taken. Local anaesthesia and antibiotic cover are used. It normally does not cause that much discomfort and there is no need for any hospital stay. There can be some blood in the urine afterwards but this usually settles without any problems.
The biopsies are studied by a pathologist who confirms whether cancer is present or not.
What is a Gleason score?
As well as confirming the presence of cancer, the pathologist will also score the cancer type. This is known as the Gleason score and it 'grades' the cancer, i.e. how aggressive the cancer is. A Gleason score can be calculated from the sum of the two most predominant cancer patterns, each of which is assigned a number from 1 to 5. These numbers indicate the degree of differentiation. This is an arbitrary amount that the tissue of the biopsy differs from that of normal healthy prostatic tissue (1=well differentiated, i.e. recognisable glandular tissue and 5=poorly differentiated, i.e. unrecognisable to glandular tissue). A Gleason score of 2 (out of ten) represents a 'latent' cancer whereas a Gleason score of 10 is seen as an aggressive cancer and will give the doctor an idea about its progression.
As well as cancer, the biopsy is also examined for prostatic intraepithelial neoplasia (PIN). This is a pre-malignant change in the prostate cells, the earliest stage in disorganised cell growth. PIN is estimated to be associated with concomitant cancer in 30-50% of cases. If only PIN is found in the biopsies the next step remains contentious but most Urologists would advocate repeat biopsies.
Are there further investigations?
Depending on the PSA value, DRE and the TRUS biopsy findings, further staging studies may be required. These will tell the doctor how advanced the cancer is and help in deciding what treatment is required.
Magnetic resonance imaging (MRI) is often used to evaluate the local spread of the cancer.
A radio-nuclide bone scan can be carried out on the whole body. This is useful in detecting bony metastases.
What is the treatment?
There are many options for the patient and this can be very confusing. Furthermore novel therapies are continuing to evolve and there is a lack of long-term data with some of the more recent therapies. In general, most Urologists will engage the patient in a detailed discussion of the available treatment options, so that an informed decision, which also takes account of individual patient preferences, can be reached.
Treatment options vary according to whether the patient has localised disease, locally advanced disease or metastatic prostate cancer.
What are the options for localised prostate cancer?
Watchful Waiting
For men over 70 and/or those with significant co-morbidity, such as angina or chronic obstructed airways disease, the option of active surveillance may be the most appropriate course of action. Indeed this may be the best option if the cancer is low volume and of a less aggressive type. Careful follow-up with regular DRE and PSA monitoring is essential. Furthermore, counselling and implementation of active treatment should occur if the cancer progresses.
Radical Prostatectomy
Having long been considered the 'gold standard' therapy, radical prostatectomy has the advantage of removing the whole of the prostate, which reduces the risk of disease recurrence. Furthermore if all the cancer tissue has been removed, it also proffers a cure. The operation is commonly done through a horizontal or vertical incision on the lower abdomen. However, a laparoscopic approach (or 'key hole') is gaining popularity through the appeal of reduced bleeding and a shorter hospital stay.
What does it involve? The operation is performed under general anaesthesia (whether the keyhole or open technique is used). The prostate is carefully dissected away from surrounding tissues. Particular care is taken to preserve the delicate nerves on either side of the prostate. The seminal vesicles (storage vessels for sperm that lie just above and behind the prostate) are removed with the prostate after their connection to the testicles (the vas) are cut. The urethra is then re-attached to the base of the bladder. Lymph nodes in the pelvis are then sampled to exclude any microscopic spread of cancer. Two drains are normally left which will be removed 2-5 days later. A catheter will be left for 2 weeks whilst the urethra and bladder heal.
What are the possible complications? There is a risk of bleeding and many men will have a blood transfusion either during or after the operation. Every man will be infertile afterwards. This is owing to the disconnection of the vasa - a vasectomy, in effect. Erectile dysfunction can affect up to 50 %, but with careful preservation of the nerves and additional help with medication (e.g. viagra), the percentage is usually a lot less. Stress incontinence is seen in a small number (2-3 %) and invariably improves with physiotherapy and/or medication over time.
What are the outcomes? Provided that the entire prostate including all the cancer has been removed the serum PSA level will fall to less than 0.1 ng/ml. The PSA should remain at this level but regular PSA checks should identify cancer recurrence.
External Beam Radiotherapy (EBRT)
Radiation therapy provides an alternative, definitive treatment approach compared to surgery. Because of the absence of a major operation it can be considered for patients with medical conditions that put them at risk for surgery.
What does it involve? The therapy is carried out in the outpatient setting. A beam of radiation is aimed at the prostate with the aim being the destruction of the cancer cells. The amount of radiation is divided into doses that are given usually over a course of 6 weeks. Pelvic lymph nodes can be included in the treatment field
What are the possible side effects? Advances in radiotherapy have led to the radiation beam being highly trained on the prostate. This has led to fewer side effects. However proctitis (inflammation of the rectum), rectal bleeding and blood in the urine can occur. There is also a small risk of incontinence (1-3 %).
What are the outcomes? In carefully selected patients EBRT offers a 15-year overall survival, similar to that observed in patients that have had a radical prostatectomy. However, if recurrence occurs then the cancer cannot usually be treated with surgery.
Brachytherapy
This technique is growing in popularity. It is the deployment of radioactive seeds directly into the prostate. It can be done as a two-stage (two visits to hospital; to be measured and then implanted with the seeds) or a one-stage procedure. In patients considered at risk at high risk of recurrence, Brachytherapy can be combined with EBRT. Brachytherapy is most suitable for patients with smaller, lower risk cancers and for men who have small or medium-sized prostates.
What does it involve? In the one-stage procedure, under a general anaesthesia, 15 to 20 needles are inserted into the prostate through the perineum (the area between the scrotum and the anus). This is done under vision via a trans-rectal ultrasound. Once the needles have been placed then a computer programme works out how many seeds need to be placed and where in order to achieve a treatment dose of radiation. The field of radiation is calculated to avoid damage to the urethra and the rectum. A catheter is normally inserted during the operation and stays in for usually 12 hours after the operation. This procedure can be carried out as a day case.
What are complications? The main problem is swelling of the prostate. This can cause worsening of lower urinary tract symptoms for some time. Therefore this procedure should be used with caution with patients with existing bladder outflow obstruction. Men who have had a previous TURP are not eligible for this procedure because the seeds are not retained satisfactorily. Most men will be put on an alpha blocker after this procedure.
What are the outcomes? The one stage technique is a fairly new development in the UK. Results from the US that have recently been published suggest that outcome of Brachytherapy is comparable to that of radical prostatectomy and EBRT.
Cryotherapy
Cryotherapy utilises very low temperatures to cause cancer cell death. It is not a common procedure but can be an option for some men.
What does it involve? The technique of Cryotherapy is similar to that of Brachytherapy. About 8-10 needles are inserted into the prostate via the perineum, under a general anaesthesia. Liquid nitrogen is then circulated along the needles to create an 'ice-ball'. The urethra is protected by running warm water, via a catheter, into the bladder.
What are the possible side effects? There have been reports of significant complications with Cryotherapy. Pain, urinary retention and erectile dysfunction have occurred. There is also the risk of the creation of a passage between the urethra and the rectum, which if severe would necessitate a large open operation the correct it.
What are the outcomes? Some studies have reported survival rates similar to those of radical prostatectomies. However no long-term randomised, controlled trials to compare Cryotherapy with established treatments have yet to be carried out.
What are the options for locally advanced prostate cancer?
This is where the cancer has spread beyond the prostate gland, to involve the seminal vesicles or the bladder, but not to the lymph nodes or bones. The PSA is normally more than 10 ng/ml and the bone scan is negative. Surgery, i.e. radical prostatectomy, tends to be less favoured in locally advanced disease and radiotherapy and hormone therapy are preferred. It is generally accepted that the treatment of locally advanced disease is no longer curative. The aims of treatment are to slow progression of the cancer and to palliate symptoms with the quality of life being a high priority. There are commonly three options: EBRT, EBRT with preceding androgen ablation and androgen ablation/hormonal manipulation.
External Beam Radiotherapy (EBRT)
EBRT is a preferred option for patients with locally advanced prostate cancer, frequently used in combination with hormonal therapy.
What does it involve? The therapy is carried out in the outpatient setting. A beam of radiation is aimed at the prostate with the aim being the destruction of the cancer cells. The amount of radiation is divided into doses that are given usually over a course of 6 weeks. Pelvic lymph nodes can be included in the treatment field.
What are the possible side effects? Advances in radiotherapy have led to the radiation beam being highly trained on the prostate. This has led to fewer side effects. However proctitis (inflammation of the rectum), rectal bleeding and blood in the urine can occur. There is also a small risk of incontinence (1-3 %).
What are the outcomes? In locally advanced disease, the survival rates at 5 years with EBRT are not as high when compared to EBRT in prostate confined disease. However, when hormonal therapy is used prior to EBRT, there is an improvement in local control and disease-free survival.
Hormonal Therapy
Hormonal therapy can be used in combination with EBRT (usually preceding it) or on its own in the management of locally advanced prostate cancer. Hormonal therapy on its own is probably the most appropriate therapy in older men with pre-existing colorectal disease.
How does Hormonal Therapy/Androgen Ablation work? Androgens (e.g. testosterone) are hormones that are essential for the normal development of the prostate. It is well known that most prostate cancers are dependant on, and are stimulated by, testosterone. 70-80 % of men with prostate cancers respond to various forms of androgen deprivation. The testicles are responsible for 95 % of the testosterone derived, with the remaining amount originating from the adrenal glands that sit on top of each kidney. The testicles and the adrenals are stimulated to produce pre-cursors that eventually become testosterone by conversion in peripheral cells. The stimulation comes from hormones released by the pituitary gland and the hypothalamus in the brain. Therefore medication can be utilised to block the production of testosterone at different levels; LHRH (Luteinizing Hormone Releasing Hormone) analogues act at the pituitary gland and anti-androgens block the action of androgens, i.e. testosterone in the body.
LHRH Analogues: These are commonly given as a three monthly depot injection. They specifically act by over-stimulating receptors in the pituitary gland and eventually blocking the release of hormones that stimulate the production of testosterone. The circulating testosterone level is reduced to castration levels. The main side effects of this drug are a reduction in sex drive and impotence. This is reversible upon stopping of the medication. They can also cause hot flushes. LHRH analogues are able to reduce the size of the cancer and slow progression. However, it does not destroy or cure the cancer.
Anti-Androgens: This medication is normally a tablet taken once a day. They block the action of testosterone on the prostate. The side effects of anti-androgens include breast enlargement and soreness. They can also cause mild stomach upset and can damage the liver. However, they do not have such a profound effect on impotence and libido compared to LHRH analogues. Anti-androgens do not offer a cure for prostate cancer, merely that they slow the progression.
What are the options for metastatic prostate cancer?
Metastatic prostate cancer is where the patient presents with widespread cancer. The PSA will often highly elevated and the MRI/CT scan will show the cancer to be beyond the confines of the gland. The local, or even distant, lymph nodes may also be enlarged. The bone scan is normally positive. Metastatic disease can also occur after attempts at curative therapy. This form of prostate cancer carries the worse outlook - about 70% of men affected will have died from their cancer within 5 years. However, there are options that can delay the progression for several years. These include:
Orchidectomy
This is the surgical removal of both testicles so that testosterone is not produced. It is a permanent, irreversible procedure.
What does it involve? This procedure can be done under a general or local anaesthesia. An incision is made in the scrotum and both testes are exposed. They are then removed with the tying off of their vessels. Prosthetic testes can be inserted as replacements for a more cosmetic appearance. It is normally a day case procedure.
What are the side effects? The main side effects are hot flushes, loss of libido and impotence. Patients will be infertile.
What are the outcomes? As with any therapy for metastatic prostate cancer, the aim is to slow the progression of the disease. It will not cure the cancer. About 80 % of men will respond to this treatment and will slow the progression for around 18 months.
LHRH Analogues
These are commonly given as a three monthly depot injection. This is an injection into the flesh of the abdomen. They specifically act by over-stimulating receptors in the pituitary gland and eventually blocking the release of hormones that stimulate the production of testosterone. The circulating testosterone level is reduced to castration levels. The main side effects of this drug are a reduction in sex drive and impotence. This is reversible upon stopping of the medication. They can also cause hot flushes. LHRH analogues are able to reduce the size of the cancer and slow progression. However, it does not destroy or cure the cancer. The response to this type of treatment is about 80 % and its benefits last around 18-36 months. When the injection is first given it can cause a large rise in the circulating testosterone. This can cause bone pain and even the cancer causing pressure on the spinal cord that may cause paralysis. For this reason, anti-androgens are given to cover this 'tumour flare'.
LHRH Analogues and Anti-Androgen in combination
This is the long-term use of LHRH analogues and anti-androgens together. This confers complete testosterone blockade. However it has not been clear with clinical trials whether this therapy significantly increases the time to progression or overall survival. The side effects include impotence, hot flushes and stomach upsets. It is felt that this combination therapy is probably best suited to younger, relatively fit men with advanced prostate cancer.
What happens if the PSA starts to rise?
As part of their follow up, patients will have regular PSA checks. After radical prostatectomy the PSA should remain at zero if all the cancer has been removed. With locally advanced and metastatic disease treated with hormones, the PSA should, initially, fall to very low levels. However, the cancers eventually become insensitive to hormone ablation and the PSA begins to rise. This is known as 'hormone escape' prostate cancer. This PSA rise often brings clinical symptoms, most commonly bone pain. Quite often a bone scan will need to be repeated to see whether there has been any spread of the cancer. If the PSA does rise there are other therapeutic options, but none of them will offer a cure.
These include:
Modifying existing hormonal therapy
An anti-androgen can be added if the patient is just on a LHRH analogue. This can improve the PSA level, but carries with it the side effects of an anti-androgen such as breast soreness and stomach upsets. Paradoxically, if the patient is on complete hormone blockade, then the stopping of the anti-androgen only may result in a temporary PSA decline.
Cytotoxic Chemotherapy
This can be an option for some patients and more and more agents are being explored. Some men find that the side effects are unacceptable for the small benefit the drugs may offer. However, the side effects can be overcome and agents such as Taxotere may be able to extend survival for months or even years.
Oestrogen
These are female hormones that appear to directly damage the cancer cell and reduce the stimulation of cancer growth. They, unfortunately, have potentially serious side effects that include blood clots and even strokes. Patients should take a daily dose of aspirin if on oestrogens. LHRH analogues should also be continued.
Bisphosphonates
These are a group of drugs normally used in the treatment of osteoporosis. However recent studies have shown that they can damage prostate cancer cells and also prevent them metastasising and adhering to bone. Furthermore they can also improve bony pain from metastases and prevent fractures. Their side effects are mild, with 'flu like symptoms being the main culprit.
Palliative Radiotherapy
Radiotherapy can be utilised if pain is localised to a specific area. This can provide relief of symptoms in up 80 % of patients. This often a short course, but can dramatically improve the quality of life.
Further information
Your local surgery is the best place for you to find information on prostate cancer, especially if you have specific concerns about your own symptoms and treatment. Cancer and prostate cancer charities can also be useful sources of information and support.
The Prostate Cancer Charity www.prostate-cancer.org.uk
Cancer Bacup www.cancerbacup.org.uk
Cancer Research Campaign www.cancerhelp.org.uk
Prostate Research Campaign UK www.prostate-research.org.uk
UK Prostate Link www.prostate-link.org.uk
