Diagnosis is not solely deciding whether a man has prostate cancer, but whether that disease requires treatment, explain Professor Mark Baker (left) and Dr John Graham

Prostate cancer is one of the commonest cancers in men. Each year there are approximately 35,000 new cases in England and Wales, and over 9000 deaths. It is predominantly a disease of older men but around 20% of cases occur in those under the age of 65 years.1,2

A review of current practice in England and Wales and elsewhere in Europe, carried out for NICE, highlighted large variations in surgical and radiotherapy treatments for early prostate cancer.3 Another recent publication summarised the wide variation in prostate cancer incidence between countries, which is principally a result of differences in rates of prostate-specific antigen (PSA) testing. The article highlights the differences in prostate cancer incidence, survival, and mortality in European countries. Austria has the highest prostate cancer incidence and 5-year survival rates but also the highest percentage of men who have had a PSA test in the past 12 months: 28% compared with 8% in England. Despite the high level of PSA testing in Austria, the prostate cancer mortality in England was slightly lower than that of Austria in 2000.4 The measured incidence of prostate cancer seems to be largely dependent on the PSA testing practice in use, rather than representing a measure of the importance of the disease.

Given the long disease course of prostate cancer, survival data are useless as a measure of the effectiveness of treatment, so the monitoring of trends and outcomes has to use mortality data (population death rates), which are falling despite the recent sharp rise in the number of reported cases. The ProtecT study5 funded by the Department of Health, which includes elements of population screening and compares specific treatments, should confirm whether increased PSA testing results in improved prostate cancer cure rates, although it will be at least 10 years before results are available.

At present, the evidence suggests that many PSA-detected prostate cancers are being overtreated.6 Perhaps the purpose of PSA testing should not be to determine whether a man has prostate cancer, but whether his disease is of a type that requires treatment. One of the major challenges we face is identifying which men with early prostate cancer need treatment.

Need for a guideline

While prostate cancer can be an aggressive and lethal disease, there is considerable uncertainty about which men should be treated. There are many with localised and relatively inactive disease whose quality or length of life will remain unaffected by the diagnosis.1 It is likely that some men with prostate cancer currently receive unnecessary radical treatment, with unpleasant and often lifelong side-effects. In addition, although there are several radical treatments (aimed at cure) available, there has been no relevant research to compare them.1

There is also understandably wide variation in local practices; for example, there is evidence of up to fourfold variation in radical prostatectomy rates and evidence of patchy availability of certain treatments and procedures across the country.1 As a result of these uncertainties, production of a clinical guideline for prostate cancer was a top priority. This article summarises the most important recommendations from the NICE guideline Prostate cancer: diagnosis and treatment, with special reference to those working in primary care.1,2 The guideline is evidence based where possible but where there was insufficient evidence, as was often the case, the recommendations are based on consensus opinion of the experts on the guideline development group.

Diagnosis

Men usually present at the GP’s surgery without any clear sign of disease and will have a digital rectal examination (DRE) and usually PSA testing in the primary care setting, as outlined in the NICE guideline on Referral guidelines for suspected cancer.1,2,7

Previous guidance to GPs, based on these NICE referral guidelines7 and on guidance from the Prostate Cancer Risk Management Programme,8 created an automatic pathway for a man with a raised PSA that involved referral to hospital, prostate biopsy, and diagnosis followed by a range of treatment options. Recommendations from the new NICE guideline amend this approach and stress the importance of including the patient, their partner, and their carer in the decision-making process. They should be given information suitable to their individual needs, which should include advice on all management options available.1,2

Biopsy

Healthcare professionals should help patients to make the decision on whether or not to have a prostate biopsy by discussing results of the PSA test, DRE, and co-morbidities. Risk factors include increasing age and ethnic origin (black African or Caribbean) and these should also be discussed. An increased PSA level alone is insufficient to trigger biopsy.

The new guideline from NICE says that the role of biopsy is to detect those cancers that might be detrimental to the patient’s health rather than picking up every cancer—some men with clinically insignificant disease, which may never cause symptoms nor have any effect on life expectancy, may not benefit from knowing about their disease. This might be considered an adverse effect of biopsy, and patients and their partner or carer should be warned before deciding on biopsy that they may have to live with the diagnosis of clinically insignificant cancer.1,2

The histological diagnosis of localised prostate cancer is usually made by ultrasound-guided transrectal biopsy because of an elevated age-specific PSA. Evidence has shown that 40% of men with a raised age-related PSA will have prostate cancer but so will 15% of men with a normal PSA. Approximately 30% of men will have prostate cancer on biopsy, with levels of 4–10 ng/ml. However, as many as 15% of men with PSA values below 4 ng/ml will also have cancer, of which some cases will be clinically significant.9 The results of all prostate biopsies should be reviewed by a urological multidisciplinary team (MDT). Many cancers diagnosed on the basis of PSA alone will be of low risk, having little or no impact on life expectancy.

Imaging

Patients with prostate cancer are not routinely referred for imaging unless radical treatment is recommended. The decision on when and how to image a patient depends on the clinical presentation and the treatment intent, and is made after classification of the patient according to their risk factor (see Table 1). Imaging methods recommended are:1,2

  • computerised tomography (CT) of the pelvis—not recommended for men with low-risk or intermediate-risk localised prostate cancer
  • magnetic resonance imaging (MRI) of the pelvis for men with high-risk localised and locally advanced prostate cancer who are being considered for radical treatment (CT if MRI is contraindicated)
  • bone scans are recommended for staging men with intermediate and high-risk localised or locally advanced disease, and for men on watchful waiting with a high risk of bone metastases. Men with low-risk localised prostate cancer should not routinely have a bone scan.

Positron emission tomography and magnetic resonance spectroscopy are not recommended for men with prostate cancer.

Localised disease

Men with localised prostate cancer (disease confined to the gland) may be eligible for radical treatment to eliminate the disease.1,2 As all treatments for prostate cancer may have severe side-effects, it is important to know the probability of the cancer causing problems in later life. A risk category will be assigned to all patients with newly diagnosed localised prostate cancer by the urological cancer MDT, and will depend on age, co-morbidities and, especially, the risk factors for progression. These are defined in Table 1.

To avoid unnecessary treatment, the guideline defines the concept of active surveillance for localised disease—radical treatment could be offered but is deferred until there is demonstrable progression of the cancer as defined by changes in PSA or Gleason grading on repeat biopsy. Strong evidence supporting this approach is lacking and clinical trials comparing active surveillance with immediate radical treatment are ongoing. Active surveillance is recommended because of the high incidence to mortality ratio (low death rate) that is a result of diagnosis of prostate cancer arising from a biopsy performed in men with marginally elevated PSA levels. If evidence of disease progression (increased PSA level or adverse biopsy results) is seen in men with localised prostate cancer who have chosen an active surveillance regimen, they should be offered radical treatment.1,2

Radical treatment

The choice of radical treatment is difficult for many men and their partners, and they should be adequately informed about the effects of the cancer and the treatment options on their sexual function, physical appearance, continence, and other aspects of masculinity. The healthcare professional must support the patient in making his treatment decisions, bearing in mind the effects on their quality of life and survival. There is a range of treatments and potential for serious side-effects, so patients who may undergo radical treatment should be given the chance to discuss them with a specialist surgical oncologist and specialist clinical oncologist.1,2

The NICE guideline does not express a preference between radical prostatectomy or radical radiotherapy, and either may be considered. The new techniques of cryotherapy and high-intensity focused ultrasound are not recommended as further evidence of their clinical effectiveness and safety is required.

Table 1: Risk stratification for men with localised prostate cancer

 
PSA (ng/ml)
 
Gleason score
 
Clinical stage
Low risk
<10
and
?6
and

T1–T2a

Intermediate risk
10–20
or
7
or

T2b–T2c

High risk
>20
or
8–10
or

T3–T4

PSA=prostate specific antigen
National Institute for Health and Care Excellence (NICE) (2008) CG 58 Prostate cancer: diagnosis and treatment. London: NICE.
Reproduced with permission. Available from www.nice.org.uk

Locally advanced disease

The disease may be considered locally advanced when it has penetrated the capsule of the prostate gland, and includes involvement of the pelvic lymph nodes. A similar approach to treatment is often used as for high-risk localised disease.

The combination of external beam radiotherapy plus hormonal therapy is the most frequently used treatment for locally advanced disease, although radical surgery may have a role in selected cases.

Adjuvant hormonal therapy with goserelin, triptorelin, and leuprorelin acetate is recommended for men with locally advanced prostate cancer who are receiving radical radiotherapy:1,2

  • for 3–6 months

or

  • for a minimum of 2 years with a Gleason score of ?8.

Relapse after radical treatment

Biochemical relapse after radical treatment is common and treatment practices are variable and of unproven benefit. In some cases, the persistence of PSA in the blood is not the result of persisting cancer but because some prostate tissue may remain after prostatectomy; in others, it is of uncertain clinical significance. It is therefore not always appropriate to rush into further treatment. Analysis of serial PSA levels should be carried out after radical treatment, using the same assay technique as before.1,2

If treatment is considered appropriate, it may be:1,2

  • radical radiotherapy to the prostatic bed for men with biochemical relapse after radical prostatectomy
  • hormonal therapy for men with biochemical relapse who have symptomatic local disease progression, any proven metastases, or a PSA doubling time <3 months—it is not routinely recommended.

Metastatic disease

Hormonal therapy causing androgen suppression is the first-line therapy for metastatic prostate cancer—luteinising hormone-releasing hormone agonist therapy for prostate cancer constitutes the highest single drug cost for cancer in the NHS. Surgical castration is more cost effective but is permanent and often less acceptable to patients. Other courses of treatment to consider are:1,2

  • bilateral orchidectomy
  • anti-androgen monotherapy with bicalutamide—men should be advised of and be willing to accept the adverse impact on overall survival and gynaecomastia in the hope of retaining sexual function
  • intermittent androgen withdrawal as an alternative to continuous androgen withdrawal, especially for men experiencing severe side-effects—they should be informed that there is no long-term evidence of its effectiveness.

When the disease becomes hormone refractory, there is evidence that chemotherapy can prolong life and improve symptoms but it needs to be given before the man’s performance status deteriorates. Prompt referral to an oncologist or palliative care specialist is indicated for men who develop biochemical evidence of hormone refractory disease.1,2

Treatment with docetaxel is recommended for men with hormone-refractory metastatic prostate cancer only if their Karnofsky performance status score is 60% or more.1,2,10

Bone is the most common site of metastatic disease in prostate cancer and the risk of spinal cord compression is high. Bisphosphonates can influence the behaviour of metastatic disease in bone, but there is insufficient evidence to support their use in preventing or delaying bone complications.1,2 However, their use for pain relief may be considered for men with hormone-refractory prostate cancer when other treatments, including analgesics and palliative radiotherapy, have failed. The choice of drug should be based on the cost and either the oral or intravenous route of administration should be chosen according to convenience, tolerability, and cost.

Treatment with strontium-89 should be considered for men with painful bone metastases from hormone-refractory prostate cancer, especially for those who are unlikely to receive myelosuppressive chemotherapy.

Complications of treatment

Significant urinary and bowel complications can occur after radical surgery and radical radiotherapy for prostate cancer, and sexual function may be impaired by radical local treatments and by hormonal therapy. Men and their partners should have early and ongoing access to specialist erectile dysfunction services. Patients suffering with incontinence after treatment should be given advice on coping strategies, and access to specialist continence services—stress incontinence refractory to treatment requires referral to a specialist surgeon for possible artificial urinary sphincter construction.

Flexible sigmoidoscopy should be used to exclude inflammatory bowel disease or malignancy of the large bowel and to ascertain the nature of the radiation injury in men with symptoms consistent with radiation-induced enteropathy. Particular caution should be taken with anterior wall rectal biopsy following brachytherapy because of the risk of fistulation.1,2 Flexible sigmoidoscopy should also be offered every 5 years as follow-up for men treated with radical radiotherapy for prostate cancer.

Follow up

The long natural history of prostate cancer requires coordination between primary and secondary care. Following radical treatment, and after 2 years at the earliest, men with a stable PSA and no significant treatment complications should be offered follow up outside hospital, for example in primary care, by telephone or email, or a combination, unless they are participating in a clinical trial that requires more formal clinic-based follow up. However, before a man is discharged from hospital follow-up, there must be pathways in place that allow direct access to the urology MDT should future problems develop.

Where patients have elected to follow a watchful waiting regimen, without beginning any curative treatment, they should normally be followed up in primary care. Protocols for this will have been agreed between the local urological cancer MDT and the relevant primary care organisation. Measurement of PSA level should be carried out at least once a year.1,2

Summary

The NICE guideline on prostate cancer has tried to offer advice where there was uncertainty, in order to improve the consistency of treatment in line with existing evidence and to reduce variations in practice. The guideline development group was disappointed with the quality of research available to guide it and has made several key recommendations for future research. The guideline offers balanced advice which will, if implemented sensitively, reduce overdiagnosis and overtreatment, while ensuring that men with ominous but curable disease will receive more reliable treatment with a greater chance of elimination of the cancer.

NICE implementation tools

NICE has developed the following tools to support implementation of its guideline on prostate cancer. They are now available to download from the NICE website: www.nice.org.uk.

Costing tools

National cost reports and local cost templates for the guideline have been produced:

  • costing reports are estimates of the national cost impact arising from implementation based on assumptions about current practice, and predictions of how it might change following implementation of the guideline
  • costing templates are spreadsheets that allow individual NHS organisations and local health economies to estimate the costs of implementation taking into account local variation from the national estimates, and they quickly assess the impact the guideline may have on local budgets.

Slide set

The slides are aimed at supporting organisations to raise awareness of the guideline at a local level and can be edited to cater for local audiences. They do not cover all the recommendations from the guideline but contain key messages, and should be used in conjunction with the Quick Reference Guide.

Audit support

Audit support has been developed to assess current practice in the management of prostate cancer compared with the guideline recommendations. Audit criteria based on key priorities for implementation in the guideline are provided, which can be adapted for use locally. Although the given standard should be aimed for, a more realistic local short-term standard can be set based on discussion with clinicians.

Implementation advice

The implementation advice document contains suggested actions for implementing the guideline. It aims to help implementers identify recommendations in the guideline that are not part of current practice, and should be used alongside the costing report and template.

  • There is as yet no consensus agreement that population screening with PSA testing will reduce mortality from prostate cancer
  • 40% of men with a raised age-specific PSA test will have prostate cancer
  • 15% of men with a normal PSA will have prostate cancer
  • Clear local referral guidance based on the NICE guideline would help practitioners know who to refer to in secondary care and when
  • Tariff costs:a
      • urology out patients = £160 (new), £79 (follow up)
      • needle biopsy prostate = £266 (out patient)
      • radical prostatectomy (MO4) = £5802
  1. National Collaborating Centre for Cancer. Prostate cancer: diagnosis and treatment. Cardiff: NCCC, 2008.
  2. National Institute for Health and Care Excellence. Prostate cancer: diagnosis and treatment. Clinical Guideline 58. London: NICE, 2008.
  3. National Institute for Health and Care Excellence. Prostate cancer: diagnosis and treatment. Evidence review. London: NICE, 2008.
  4. Autier P, Boniol M, Héry C et al. Cancer survival statistics should be viewed with caution. Lancet Oncol 2007; 8 (12): 1050–1052.
  5. Donovan J, Hamdy F, Neal D et al. and the ProtecT Study Group. Prostate testing for cancer and treatment (ProtecT) feasibility study. Health Technol Assess 2003; 7 (14): 1–88.
  6. Bangma C, Roemeling S, Schröder F. Overdiagnosis and overtreatment of early detected prostate cancer. World J Urol 2007; 25 (1): 3–9.
  7. National Institute for Health and Care Excellence. Referral for suspected cancer. Clinical Guideline 27. London: NICE, 2005.
  8. www.cancerscreening.nhs.uk/prostate/informationpack.html
  9. Raaijmakers R, Wildhagen M, Ito K et al. Prostate-specific antigen change in the European randomized study of screening for prostate cancer, section Rotterdam. Urology 2004; 63 (2): 316–320.
  10. National Institute for Health and Care Excellence. Docetaxel for the treatment of hormone-refractory metastatic prostate cancer. Technology Appraisal 101. London: NICE, 2006.G