Diagnosis and treatment of prostate cancer: summary of NICE guidance
BMJ 2008; 336 doi: https://doi.org/10.1136/bmj.39498.525706.AD (Published 13 March 2008) Cite this as: BMJ 2008;336:610
This article has a correction. Please see:
- John Graham, lead consultant in clinical oncology1,
- Mark Baker, lead cancer clinician2,
- Fergus Macbeth, director3,
- Victoria Titshall, project manager3
- on behalf of the Guideline Development Group
- 1Taunton & Somerset NHS Foundation Trust, Musgrove Park Hospital, Taunton TA1 5DA
- 2Leeds Teaching Hospitals NHS Trust, St James’s University Hospital, Leeds LS9 7TF
- 3National Collaborating Centre for Cancer, Cardiff CF10 3AF
- Correspondence to: J Graham john.graham{at}nhs.net
Why read this summary?
Prostate cancer is one of the commonest cancers in men. Each year there are about 35 000 new cases in England and Wales and over 9000 deaths. The clinical course can extend over many years and often involves many different healthcare professionals. Evidence exists of practice variation around the country and of patchy availability of certain treatments and procedures. This article highlights a selection of the most recent recommendations from the National Institute for Health and Clinical Excellence (NICE) on the diagnosis and treatment of prostate cancer.1
Recommendations
NICE recommendations are based on systematic reviews of the best available evidence. When minimal evidence is available, recommendations are based on the guideline development group’s opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets.
Informed decision making
Men with prostate cancer can be faced with multiple treatment choices over many years. Healthcare professionals should:
Adequately inform men with prostate cancer and their partners or carers about the effects of prostate cancer and the treatment options on their sexual function, physical appearance, continence, and other aspects of masculinity. [Based on evidence from qualitative studies and the experience of the Guideline Development Group (GDG)]
Support men and their partners or carers in making treatment decisions, taking into account the effects on quality of life as well as survival. [Based on the experience of the GDG]
Ensure that mechanisms are in place to allow men with prostate cancer and their primary care providers to gain access to specialist services throughout the course of their disease. [Based on the experience of the GDG]
Diagnosis
To help men decide whether to have a prostate biopsy, discuss with them their prostate specific antigen (PSA) level, digital rectal examination findings, age, black African or black Caribbean ethnicity (associated with an increased risk of prostate cancer), and comorbidities (which may affect your decision to offer curative treatment), together with any history of a previous negative prostate biopsy.[Based on evidence from high quality observational studies] The serum PSA level alone is a poor predictor of the presence of prostate cancer and should not automatically lead to a prostate biopsy; moreover, many cancers diagnosed on this basis alone will be of low risk, causing little or no impact on life expectancy.
The results of all prostate biopsies should be reviewed by a urological cancer multidisciplinary team. Men should only have a repeat biopsy after a review by this team of the risk characteristics, including life expectancy, PSA level, digital rectal examination, and prostate volume. [Based on the experience of the GDG]
Localised disease
Urological cancer multidisciplinary teams should assign a risk category (table⇓) to all men with newly diagnosed localised prostate cancer. [Based on evidence from high quality cohort studies of outcome after treatment]
Risk stratification for men with localised prostate cancer
One of the greatest challenges in prostate cancer is deciding which men have rapidly growing cancers that need treating and which men have indolent cancers that will never trouble them.
Given the range of treatments and their serious side effects, men with prostate cancer who are candidates for radical treatment should have the opportunity to discuss their treatment options with a specialist surgical oncologist and a specialist clinical oncologist. [Based on the experience of the GDG]
Men having radical external beam radiotherapy for localised prostate cancer should receive a minimum dose of 74 Gy to the prostate at no more than 2 Gy per fraction. [Based on evidence from high quality randomised controlled trials]
The new techniques of cryotherapy and high intensity focused ultrasound are not recommended outside clinical trials as further evidence of their long term clinical effectiveness and safety is required.
Low risk
For men with low risk, localised prostate cancer (table⇑) who are considered suitable for radical treatment, first offer active surveillance (measurement of PSA level and repeat biopsies). [Based on the experience of the GDG] Such surveillance is recommended (rather than immediate radical treatment) because of the low mortality in men with marginally raised PSA levels, but for a small proportion of men with low risk disease, surveillance may not be appropriate. Changes in PSA level and Gleason grade are important prognostic factors and may identify cancers that require radical treatment.
For men with localised prostate cancer who have chosen an active surveillance regimen and who have evidence of disease progression (that is, a rise in PSA level or adverse findings on biopsy), offer radical treatment. [Based on the GDG’s opinion of what constitutes good practice]
Thus radical treatment is offered in active surveillance but deferred until there is evidence of progression of the cancer as defined by changes in PSA levels or Gleason histological grading on repeat biopsy.
Intermediate risk
Intermediate risk, localised prostate cancer can be treated with radical surgery, radical radiotherapy, or active surveillance.
High risk
Active surveillance is not recommended for men with high risk, localised prostate cancer. [Based on the experience of the GDG]
Offer radical prostatectomy or external beam radiotherapy to men with high risk, localised prostate cancer when there is a realistic prospect of long term disease control. [Based on evidence from observational studies and on the experience of the GDG]
Relapse after radical treatment
Biochemical relapse (a rising PSA level) alone should not necessarily prompt an immediate change in treatment but should trigger serial measurements of PSA to calculate the PSA doubling time. [Based on evidence from longitudinal studies]
For men with biochemical relapse after radical prostatectomy who have no known metastases, offer early radical radiotherapy to the prostate bed. [Based on evidence from high quality randomised controlled trials]
Hormonal therapy is not routinely recommended for men with biochemical relapse unless they also have symptomatic local disease progression or any proved metastases or a PSA level that has doubled in less than three months. [Based on indirect evidence from a Cochrane review]
Hormonal therapy
Offer bilateral orchidectomy to all men with metastatic prostate cancer as an alternative to continuous luteinising hormone-releasing hormone agonist therapy (gonadorelin analogue therapy). [Based on evidence from high quality randomised controlled trials]
Offer intermittent androgen withdrawal with the caveat that there is no long term evidence of its effectiveness but it may reduce side effects such as hot flushes. [Based on evidence from non-randomised trials and on the experience of the GDG]
Hormone refractory disease and palliative care
When men with prostate cancer develop biochemical evidence of disease refractory to hormone therapy, their treatment options should be discussed by the urological cancer multidisciplinary team with a view to seeking an oncological and/or specialist palliative care opinion as appropriate. [Based on the experience of the GDG]
For men with metastatic prostate cancer, offer tailored information and access to specialist urology and palliative care teams so that their specific needs can be tackled. They should have the opportunity to discuss any important changes in their disease status or symptoms as these occur. [Based on the experience of the GDG]
Evidence exists that chemotherapy can prolong life and improve symptoms but that it should be given before the man’s performance status (general wellbeing) deteriorates. [Based on evidence from high quality randomised controlled trials] Docetaxel chemotherapy is recommended, within its licensed indications, as a treatment option for men with hormone refractory metastatic prostate cancer only if their Karnofsky performance status score is 60% or more (requiring occasional assistance, but able to care for most personal needs). [Based on evidence from high quality randomised controlled trials]
Bone metastases
The use of bisphosphonates to prevent or reduce the complications of bone metastases in men with hormone refractory prostate cancer is not recommended owing to insufficient evidence of efficacy. However, consider bisphosphonates for pain relief in such cases when other treatments (including analgesics and palliative radiotherapy) have failed. The oral or intravenous route of administration should be chosen according to convenience, tolerability, and cost. [Based on evidence from a Cochrane review].
Strontium-89 should be considered for men with hormone refractory prostate cancer and painful bone metastases, especially those men who are unlikely to receive myelosuppressive chemotherapy. [Based on evidence from high quality randomised controlled trials]
Men with hormone refractory prostate cancer shown to have extensive disease in the spine (for example, on a bone scan) should have magnetic resonance imaging of the spine if they develop any spinal related symptoms, as the risk of spinal cord compression is high. [Based on evidence from non-randomised trials]
Treatment complications
For men treated with radical radiotherapy, offer follow-up with flexible sigmoidoscopy every five years as an alternative to faecal occult blood testing in the bowel screening programme. [Based on the experience of the GDG and on advice from clinical specialists]
Healthcare professionals should ensure that men with troublesome urinary symptoms after treatment have access to specialist continence services. [Based on evidence from randomised trials and on the experience of the GDG]
Offer early and ongoing access to specialist erectile dysfunction services to men and their partners. [Based on the experience of the GDG]
Follow-up
For men who have had stable PSA levels for at least two years after radical treatment and no significant treatment complications, offer follow-up outside hospital (for example, in primary care) by secure electronic communications, unless taking part in a clinical trial that requires formal, clinic based follow-up. Offer direct access to the urological cancer multidisciplinary team. [Based on the experience of the GDG]
For men with localised prostate cancer who have chosen a watchful waiting regimen with no curative intent (whereby hormonal therapy is withheld until there is significant disease progression), arrange follow-up in primary care in accordance with locally agreed protocols. Measure the men’s PSA levels at least once a year. [Based on the experience of the GDG]
Overcoming barriers
Many of these recommendations have cost implications. A costing tool developed by NICE is available now, and an implementation pack will be available shortly. Most of the recommendations can be implemented by the multidisciplinary urological cancer teams under the supervision of the cancer networks.
Further information on the guidance
Background
After the publication of the NICE guidance on improving outcomes in urological cancers,2 each cancer network in England and all designated local and specialist urological cancer teams were reviewed by a team of clinical peers to monitor their progress in changing service organisation and delivery as had been recommended.
These reviews found that implementation of the guidance was slow and incomplete, with almost a third of networks not having compliant action plans for such implementation. This was mostly due to the designated, specialist urological cancer teams serving populations of less than one million.
Local urology cancer teams performed particularly poorly for attendance of core members at multidisciplinary team meetings, cover arrangements, referral guidelines, patient experience, and service improvement.
The reviews also found frequent failure to comply with the key recommendation that surgeons should perform no fewer than five radical prostatectomies a year, and a fourfold regional variation in the rate of radical prostatectomies between the cancer networks (not due to age differences between networks or changes in the age structure of the population). Most prostatectomies recorded in the British Association of Urological Surgeons’ cancer registry are performed in men with a Gleason score of 6 or 7 (that is, lower grade tumours) rather than being reserved for those with intermediate or high risk tumours or those with low risk tumours showing signs of progression (see www.baus.org.uk).
The large number of radiotherapy procedures carried out in patients with lower grade tumours suggests that radical radiotherapy is a more common treatment than prostatectomy (see data of the South West Public Health Observatory (www.swpho.nhs.uk/) and the radiotherapy episode statistics dataset provided by NATCanSAT at www.canceruk.net/). Clear differences in the patterns of dose and fractionation occur across the NHS, indicating a variation in practice (see the radiotherapy episode statistics dataset provided by NATCanSAT at www.canceruk.net/).
Methods
The development of this guideline was based on methods outlined by the NICE guidelines manual (www.nice.org.uk/page.aspx?o=114219). A team of health professionals, lay representatives and technical experts known as the Guideline Development Group, with support from the staff of the National Coordinating Centre for Cancer, developed this clinical guideline. The basic steps in the process of developing a guideline are as follows:
Use the remit from the Department of Health, define the scope that sets the parameters of the guideline
Form the guideline development group
Develop clinical questions
Systematically search for the evidence
Critically appraise the evidence
Incorporate health economic evidence
Distill and synthesise the evidence and write recommendations
Agree the recommendations
Structure and write the guideline
Invite stakeholder organisations to comment on a draft of the guideline
Revise the draft as appropriate to take account of the comments received
Update the guideline, if necessary, after four years.
Four different versions of the guideline have been produced: a full version containing all the evidence and the recommendations; a quick reference guide; a version known as the “NICE guideline,” which lists the recommendations; and a lay translation of the NICE guideline for patients and the public. All the versions are available from the NICE website.1
Future research
The Guideline Development Group also made the following research recommendations.
Further research is required into the identification of prognostic indicators to differentiate effectively between men who may die with prostate cancer and those who may die from prostate cancer.
The greatest uncertainties in managing prostate cancer centre on the identification of which cancers are of clinical importance and on the choice of radical treatment, and in which settings treatments are appropriate.
With the diagnosis of prostate cancer increasing in asymptomatic men, it is of growing importance to know which of these men are likely to benefit from aggressive treatment.
Research is required into the clinical and cost effectiveness of treatments aimed at the elimination of disease in men with localised prostate cancer, locally advanced disease, and locally recurrent disease. This research should include a rigorous examination of the value of procedures such as brachytherapy (localised disease only), cryosurgery, and high intensity focused ultrasonography, as well as combinations of surgery and radiotherapy with hormonal therapy and chemotherapy. The end points should include survival, local recurrence, toxicity, and quality of life outcomes.
A wide and growing range of radical treatments aimed at the eradication of disease are available. Although long term follow-up data are available for some of these in the localised disease setting, no randomised trials have compared these treatments and little evidence exists to support their use in locally advanced disease or localised recurrent disease.
Footnotes
This is one of a series of BMJ summaries of new guidelines, which are based on the best available evidence; they will highlight important recommendations for clinical practice, especially where uncertainty or controversy exists.
Contributors: All authors contributed to reviewing the evidence and writing and editing the article.
Funding: The National Collaborating Centre for Cancer was commissioned and funded by the National Institute for Health and Clinical Excellence to write this summary.
Competing interests: MB has received consultancy fees from Roche and Pfizer and advisory fees from Speciality European Pharma, and he has attended advisory boards for Pharmion. JG has received advisory fees from Speciality European Pharma, honorariums from Sanofi-Aventis, and conference expenses from Bayer Pharmaceuticals, Sanofi-Aventis, AstraZeneca; he has also been principal investigator of trials funded by Boehringer Ingelheim, Immunicon, Cell Genesys, GPC Biotech, and Sanofi-Aventis. FM is chief investigator of a national trial partly funded by Pfizer. The Guideline Development Group complied with NICE’s policy on declarations of interests for bodies that produce guidance.
Provenance and peer review: Commissioned; not externally peer reviewed.