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Prostate cancer
General Practitioner, Leeds
E-mail: will.bolland{at}doctors.org.uk
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Abstract |
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TOP
Abstract
The GP curriculum and...Prostate cancer is the most common cancer in men—it accounts for approximately 23% of all new male cancer diagnoses and is responsible for 13% of cancer deaths in men, second only to lung cancer (24%). Approximately, 34 986 new cases are diagnosed each year and 10 000 men die from prostate cancer every year in England and Wales. It is predicted to overtake lung cancer as a cause of death in the future. Worldwide it is the sixth most common cancer. The incidence varies widely by ethnic group around the world. The lifetime risk of being diagnosed with prostate cancer in the UK is 1 in 14 men (though many more will die with undiagnosed prostate cancer). It is estimated that 15–30% of men over 50 will have histological evidence of prostate cancer. At 80 years, approximately two-thirds will have detectable prostate cancer. Despite this high prevalence only one in four will die from the disease, hence the phrase ‘Men are more likely to die with prostate cancer than from it’.
Prostate cancer is part of Gender-specific health issues—Men's health, section 10.2, of the GP curriculum and as a cancer is part of Care of people with cancer and palliative care, section 12 of the GP curriculum. Table 1 in the previous article on benign prostatic hypertrophy, summarizes the learning objectives for the Men's health curriculum that relate to the topics of benign prostatic hypertrophy (BPH) and prostate cancer. Specific to prostate cancer, and drawing from both sections of the curriculum, a GP should be able to demonstrate the following:
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Risk factors |
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The causes of prostate cancer are not well understood. It is thought that hormones play a role since tumours regress with androgen deprivation, however, there are a number of known risk factors for developing prostate cancer which are summarized in table 1.
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Classification |
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The simplest classification framework that is used to inform prognosis and treatment is:
- Clinically localised disease—cancer thought, after clinical examination, to be confined within the prostate gland capsule
- Locally advanced disease—cancer that has spread outside the capsule of the prostate gland but has not yet spread to other organs
- Metastatic prostate cancer—cancer that has spread outside the prostate gland to local, regional or systemic lymph nodes (LN), seminal vesicles or other body organs (e.g. bone, liver and brain).
Other classification systems are discussed later.
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Symptoms and signs |
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Localised cancer
Localised disease is usually symptomless. Prostate cancer, unlike benign prostatic hypertrophy, usually develops in the outer part of the prostate (Fig. 1). The tumours have to be large enough to cause a pressure effect on the bladder or urethra, thus causing lower urinary tract type symptoms. Symptomless cases are usually detected following an incidental finding of a raised PSA or a hard nodule is sometimes felt in the prostate on rectal examination.
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Locally advanced disease
Like localised cancers, locally advanced tumours are often asymptomatic. Presenting symptoms may be: lower urinary tract symptoms (LUTS), urinary retention, haematuria, lower extremity oedema and/or sexual dysfuntion. On rectal examination, the prostate is likely to be hard, non-tender and with a loss of sulcus definition.
Metastatic disease
About 20–30% of cases in the UK present with symptoms of metastatic disease, usually with bone pain. Signs and symptoms depend on the site of metastases and may include: malaise, weight loss, bone pain, pathological fractures, spinal cord compression and ureteric obstruction (leading to renal failure).
| There is no good evidence that the presence of LUTS is predictive of localised prostate cancer. Experts have not agreed as to whether an ‘opt in’ or ‘opt out’ approach to PSA testing in men with LUTS should be adopted. It is recommended that all men with LUTS have the implications of PSA testing discussed with them.
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Prognosis |
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Whether a man diagnosed with prostate cancer dies from it, or from another cause, depends on two things:
- Life expectancy (which may depend on age or health)
- Type of prostate cancer
Prostate cancers are very heterogeneous in their natural history. Some will grow very slowly and never show any symptoms before the patient dies of other causes. At the other extreme, some grow and become symptomatic quickly, leading to the death of the patient. Other patients may have tumours that grow at an intermediate rate that may or may not reduce quality or duration of life. In some patients of advanced age, even aggressive tumours may have no impact on survival.
Overall Five-year survival rates are as follows:
- Stage 1 or 2—tumour confined within the prostate—65–98%
- Stage 3—tumour has breached the capsule of the prostate—60%
- Stage 4—spread to LNs, within the pelvis or elsewhere—20–30%
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Investigation |
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A digital rectal examination (DRE) and a PSA test (after counselling) are recommended for patients with any of the following unexplained symptoms:
- Inflammatory or obstructive LUTS
- Erectile dysfunction
- Haematuria
- Lower back pain
- Bone pain
- Weight loss, especially in the elderly
Postpone DRE until after the PSA test is done. Exclude urinary tract infection (UTI) before PSA testing and postpone the PSA test for 1 month after the treatment of a proven UTI.
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Screening |
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A screening programme for prostate cancer has been considered and rejected by the Department of Health in the UK. The decision was based on the available evidence of benefits and risks. In 1968, Wilson and Junger, of the World Health Organisation, developed 10 principles that should govern a national screening programme. The one criterion that a screening programme for prostate cancer fulfilled was that prostate cancer is an important health problem. Other factors like an acceptable level of sensitivity and specificity of the test, a good understanding of the natural history of the condition and a clear demonstrable benefit of early treatment are not met.
Problems with screening
- Incidental post-mortem evidence of prostate cancer is high (up to 75% of men over the age of 75 years), very few become clinically evident, so many more men would be found with prostate cancer by screening than would die or have symptoms from it
- The natural history of prostate cancer is not understood—there is no means to detect which ‘early’ cancers become more widespread
- Inadequate screening tests (see below)
- It is not clear if early treatment enhances life expectancy
- Peak incidence of morbidity and mortality is in old age (75–79 years) so potential years of life saved by screening are small
Screening tests
Several screening tests for prostate cancer are available:
- Prostate specific antigen - see boxes 1, 2 and 3
- Reproduced with permission from Oxford General Practice Library: Men's health.
- Digital rectal examination - this is operator dependent. It fails to detect early prostate cancers and lacks specificity Annual screening in Germany and the USA has not decreased mortality
- Transrectal ultrasound - too expensive for widespread use
Box 1. PSA testing
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Box 2. Taking the PSA test
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| Box 3. Sources of information and support for patients and their carers National screening, website www.cancerscreening.nhs.uk Cancerbackup, Tel. 0808 800 1234, website www.cancerbackup.org.uk Cancer Research UK, Tel. 0800 226 237, website www.cancerhelp.org.uk Prostate cancer charity, Tel. 0800 074 8383, website www.prostate-cancer.org.uk Prostate cancer support association, Tel. 0845 601 0766, website www.prostatecancersupport.co.uk UK Prostate Link, website www.prostate-link.org.uk
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The most effective screening regime involves rectal examination and PSA testing followed by Transrectal ultrasound (TRUS) for suspicious lesions. Optimal screening interval is unknown but serial screening does increase detection.
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Referral |
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Refer Urgently - to be seen by a team specialising in treatment of prostate cancer within 2 weeks if:
- Rectal examination—hard, irregular prostate typical of prostate cancer. PSA result should accompany the referral.
- Rectal examination—normal prostate, but rising/raised age-specific PSA with or without LUTS. Consider discussion with a specialist and the patient (and/or carer) before referral for very elderly patients or those compromised by other co-morbidities.
- Symptoms and high PSA levels
- For asymptomatic men with borderline, age-specific PSA results (see table 2), repeat the PSA test after 1–3 months. If the PSA level is rising, refer the patient urgently.
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Referral is not needed if the prostate is simply enlarged and the PSA is in the age-specific reference range.
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Secondary care investigations |
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TRUS guided prostate biopsy
Involves taking 6–10 cores of prostate tissue through the rectum under ultrasound guidance. If a lesion is seen, then a biopsy of the lesion will be taken directly under TRUS guidance.
Limitations
- Approximately two-thirds of men who have a TRUS biopsy due to an elevated PSA are found not to have cancer.
- Most men describe TRUS as uncomfortable or painful.
- The biopsy procedure can cause considerable anxiety.
- Up to 20% of tumours are missed—partly because many are indistinguishable from normal tissue on ultrasound.
Management of men with a negative biopsy but persistently elevated PSA is difficult—extended follow-up and possible re-biopsy causes significant anxiety.
Complications
Post-biopsy complications include:
- Bleeding—reported rates of bleeding and infection vary widely. One study reported admission rates for complications of 0.4%.
- Infection—rates of septic complications despite prophylatic antibiotic use vary from negligible to over 1%
- Haematospermia and/or haematuria—two-third men will get haematuria and/or haematospermia in the 3 months after biopsy.
| NICE guidance on TRUS The aim of the prostate biopsy is to detect prostate cancers with the potential for causing harm rather then detecting each and every cancer. Men with clinically insignificant prostate cancers that are unlikely to cause symptoms or affect life expectancy may not benefit from knowing that they have the disease. Indeed, the detection of clinically insignificant prostate cancer should be regarded as an under recognized adverse effect of biopsy.
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Further investigations
CT or MRI of pelvis would not routinely be considered unless the patient has high-risk localised disease or more advanced disease, where treatment is contemplated.
Isotope bone scan is done when watchful waiting is chosen as these patients are at higher risk of developing bone complications.
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Further classification |
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Once investigations are complete more detailed classification, that will inform prognosis and management strategy, can be made.
Histology
The Gleason Score characterizes prostate cancers on the basis of histological findings that indicate the risk of the tumour spreading. The lower the score, the less likely the cancer will spread:
- A Gleason score of six or less means that the cancer is unlikely to spread
- A Gleason score of seven means that there is a moderate chance of the cancer spreading
- A Gleason score of eight or above means that there is a significant chance that the cancer will spread
Clinical staging
In the UK, the tumour, node, metasis (TNM) classification is commonly used to stage prostate cancer (Table 3).
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Stratification of localised disease
Localised disease is subdivided according to risk of recurrence/progression on the basis of PSA, Gleason score and TNM stage (Table 4).
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Treatment of symptomless local disease |
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Treatment is controversial. There are two arguments:
The picture is further complicated as more than 50% of men over 50 years who die from other causes are found post-mortem to have prostate cancer—prostate cancer kills only a small minority of men who have it. The personal and economic cost of treating men whose cancer would never have caused them any problems must be considered.
Options
Watchful waiting
Used in men who are low risk and not suitable for active treatment. Treatment is only considered if and when they develop symptoms. It involves monitoring patients with PSA testing/rectal examination. An increase in PSA or size of nodule triggers active treatment. At 10 years follow up less than 10% with moderately well-differentiated cancer will have died from their cancer. Progression rates are higher in patients with poorly differentiated cancer.
The benefits of this approach are that it is non-invasive and avoids unpleasant side effects. The drawbacks are that some men will develop metastatic disease and some men find the uncertainty of waiting difficult to cope with.
Active surveillance
Used in men with low or intermediate risk, localised prostate cancer. Aims to target radical treatment only at those who would most benefit from it. It involves monitoring patients with PSA testing and at least one re-biopsy.
NICE guidance on active surveillance
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Radical prostatectomy
Has potential for cure, but up to 40% have evidence of incomplete tumour removal—50% of these go on to develop biochemical or clinical recurrence. In the age group most affected by prostate cancer, operative mortality is a risk, but now less than 1%. Other common complications include impotence (20–80%), and incontinence (4–21% for mild, 0–7% for total incontinence at 18 months).
NICE guidance on radical prostatectomy.
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Radical radiotherapy and external beam radiotherapy
Radical radiotherapy aims to achieve cure, but persistent cancer is found in 30% on biopsy. Short-term side effects—bladder and bowel related and include dysuria (which can be severe), urgency and increased frequency of micturition and radiation induced diarrhoea. Long-term side effects include:
- impotence (25–60%)
- incontinence (up to 5%).
- diarrhoea/bowel problems needing treatment (10%)
- occasional rectal bleeding (30%)
NICE guidance—recommended in men after radical treatment of Gleason score  8 disease, for at least 2 years.
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Brachytherapy
Brachytherapy involves insertion of radioactive seeds directly into the prostate gland. NICE does not recommend its use for localised disease.
Hormone treatment
Adjuvant hormone therapy is increasingly used in localised disease, either in conjunction with radiotherapy or following surgery where there are poor prognostic indicators (this includes patients with positive resection margins).
Neither high intensity ultrasound treatment nor cryotherapy is currently recommended by NICE for treatment of localised prostate cancer.
Monitoring following treatment of localised disease
Followup after treatment of localised disease is agreed locally. NICE recommends primary care follow up once the patient has been stable for at least two years with annual PSA tests on a long-term basis.
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Treatment of locally advanced disease |
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Luteinizing hormone releasing hormone (LHRH) analogues
LHRH analogues, such as Goserelin, are given by subcutaneous implantation every 4-12 weeks depending on the preparation used. Testosterone levels are reduced to the level of castrated men in less than 2 months. Side effects include: impotence, hot flushes, gynaecomastia, local bruising and infection around the injection site. When starting LHRH analogues, luteinizing hormone level intially increases, which can cause increased tumour activity or ‘flare’. This is counteracted by prescription of anti-androgens (e.g. flutamide) for a few days before administration of the first dose of LHRH and concurrently for the first 3 weeks. The response in most patients lasts for 12–18 months.
Anti-androgens
Anti-androgens, such as cyproterone acetate, flutamide and biclutamide, do not suppress androgen production completely. They are used to prevent side effects due to testosterone flare during initiation of LHRH analogues, as monotherapy in those who find LHRH analogues unsuitable, and in combination with LHRH analogues to produce maximum androgen blockade (monitor liver function if used long term).
Surgical castration
Reduces testosterone secretion permanently without the need for medication. Cheap and fewer side effects than other options, but rarely used in the UK any longer.
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Bony metastases |
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NICE guidance for management of metastatic prostate cancer is summarised in Fig. 3. Bilateral orchidectomy should be offered to all men as an alternative to long-term LHRH therapy. If a patient wishes to retain sexual function, despite poorer survival statistics, then anti-androgen monotherapy should be offered. Radioactive strintium reduces the number of new sites of bone pain developed. Trials of a new drug, abiraterone, have shown promising results and may prolong survival for patients with metastatic disease, but trials are still at an early stage and widespread availability is not expected for at least three years.
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Complications and side effects
Management of complications of prostate cancer and side effects of medication are summarised in Fig. 4.
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Key points
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References |
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