|NICE Clinical Guideline 58 on the diagnosis and treatment of prostate cancer has been awarded the NHS Evidence Accreditation Mark.
This Mark identifies the most robustly produced guidance available. See evidence.nhs.uk/accreditation for further details.
Although prostate cancer is now one of the most common cancers in men and approximately 35,000 UK individuals will be diagnosed annually,1 most GP practices will only be managing a handful of patients with this disease. Cancer of the prostate accounts for nearly one-quarter of all newly diagnosed cancers in men.2 It is the second most common cause of cancer-related death in men and is responsible for about 12% of all cancer deaths in men.2 Around 60% of cases of prostate cancer occur in men aged over 70 years and 20% in men below the age of 65 years.1,3 With effective treatment, over 70% of men with newly diagnosed prostate cancer now survive beyond 5 years.4
This article is timely because it coincides with advice from the Prostate Cancer Advisory Group (PCAG), which has published five key points on prostate cancer that it expects every GP to know (see Box 1).5 The PCAG was set up following the establishment (by key voluntary sector and professional groups committed to tackling prostate cancer) of the Prostate Cancer Charter for Action in January 2003. The overall remit of the PCAG is to facilitate collaboration between the Department of Health, the voluntary sector, and patient and professional groups; and to advise ministers, the National Cancer Director, and the Department of Health on the development of policy on prostate cancer. It was the first such disease-specific group of its kind, and this model has now been duplicated in other diseases, such as lung and bowel cancer.5
|Box 1: Five key facts that every GP should know5|
|PSA=prostate specific antigen|
Diagnosing prostate cancer
The NICE guideline on prostate cancer was published in 2008 as Clinical Guideline 58.1 This document begins by stressing the need for patient-centred care and good communication, while taking into account individual needs and preferences.1
Men who present with symptoms of suspected cancer should be offered a digital rectal examination (DRE) and a prostate specific antigen (PSA) test before referral to specialist care as set out in the NICE referral guidelines for suspected cancer.6 The Prostate Cancer Risk Management Programme (PCRMP) states clearly that any man who wishes to have a PSA test should be offered one, after appropriate counselling and guidance.7 Information on the advantages and disadvantages of PSA testing is available in the prostate cancer risk management programme pack for GPs, which was sent out 3 years ago to every GP in the UK, and can be ordered from the Department of Health website.8
The PCRMP recommends that age-related referral values are used to interpret PSA test results (see Table 1).6 Age-specific reference ranges for PSA are currently under review and will be updated in the NICE guidance on referral for suspected cancer, which is due to be published in 2014.9
An abnormal PSA level should not result in an automatic prostate biopsy.1 Healthcare professionals should discuss the following to help men decide whether to have a biopsy or not:1,7
- the PSA level
- findings from the DRE (e.g. prostate size)
- life expectancy
- any previous biopsy findings.
A history of prostatitis or urinary tract infection will also be very relevant.
The quality of magnetic resonance imaging (MRI) for assessment of prostate disease has improved considerably and is normally performed as a staging procedure at least 4 weeks after a biopsy. The 4-week gap is left because of artefact features caused by the biopsy tracts.10 The current trend of carrying out an MRI scan prior to biopsy—to try to assess the true extent of the tumour and allow a more targeted biopsy technique—is being assessed in a research setting.11 Bone scanning is also used for staging in certain circumstances.1
More accurate staging of prostate cancer can be obtained by means of high-intensity (template) biopsy, which is performed by the transperineal approach.12 Current evidence on the efficacy of transperineal template biopsy of the prostate shows an increase in diagnostic yield in patients with suspected prostate cancer who have had negative or equivocal results from other biopsy methods. There are no major safety concerns and NICE states that this procedure may be used for this indication provided that normal arrangements are in place for clinical governance, consent, and audit.12
|Table 1: Age-specificreference values for total PSA levels7*|
|Age (years)||PSA referral value (ng/ml)|
| PSA=prostate specific antigen
*Currently recommended by the Prostate Cancer Risk Management Programme
Management of prostate cancer
The main options following diagnosis of prostate cancer are shown in Figure 1.
Localised prostate cancer
Men with localised prostate cancer should be assigned to a risk category—low, intermediate, or high—based on:1
- PSA level
- Gleason score
- clinical stage.
Treatment options for localised prostate cancer include:1
- watchful waiting
- active surveillance
- conformal radiotherapy
- cryotherapy (in a research setting)
- high-intensity focused ultrasound (in a research setting).
Watchful waiting may be appropriate if there is significant co-morbidity and a short life expectancy. Active surveillance is being used increasingly in men with low-risk cancer, but entails regular PSA testing, DRE, biopsy, and imaging procedures.1 Radiotherapy should be considered in men who have positive margins (i.e. the finding of cancer cells at the cut edge of the radical prostatectomy specimen).
A multidisciplinary team (MDT) will help candidates receive balanced information on radical treatment options.
Locally advanced prostate cancer
The treatment of choice for locally advanced prostate cancer is luteinising hormone-releasing hormone agonist (LHRHa) therapy. Neoadjuvant and concurrent LHRHa therapy is recommended for 3 to 6 months in men receiving radical radiotherapy for locally advanced prostate cancer. Adjuvant hormonal therapy is recommended for a minimum of 2 years in men receiving radical radiotherapy for locally advanced prostate cancer who have a Gleason score of ?8.1.1
Pelvic radiotherapy should be considered if the risk of lymph node involvement is >15%.1
Radical surgery and the post-surgical hormonal approach can improve survival rates in locally advanced prostate cancer. This approach can also be combined with the use of a neoadjuvant hormonal treatment.13
Hormone-refractory prostate cancer
Hormone-resistant prostate cancer is defined by a rising PSA in spite of a testosterone level in the castrate range. However, the patient may still respond to alternative hormone manipulations.
If the prostate tumour has become castration-independent, the MDT should discuss the next therapeutic step.
Docetaxel, a chemotherapy drug, is a possible treatment option for men who fulfil the criteria outlined in NICE Technology Appraisal 101.14 A technology appraisal on abiraterone,15 which is also being investigated in the STAMPEDE trial,16 is currently in development. The use of cabazitaxel for men with hormone-refractory metastatic prostate cancer who have previously been treated with docetaxel has not been recommended by NICE.17
Intractable pain caused by metastatic bone disease can be managed by neural or neuroaxial blockade, percutaneous cordotomy, neurolytic procedures, vertebroplasty, intrathecal/epidural drug delivery, and implantable systems.18
The need for palliative care should be considered.1 Appropriate arrangements can be made according to local facilities, and based on guidance from the Gold Standards Framework19and the Liverpool Care Pathway,20 and a discussion held about preferred priorities of care.
|Figure 1: Management options for prostate cancer7*|
Adverse effects of treatment
Before starting any therapies for prostate cancer, men should be informed that treatment may result in altered physical appearance, particularly if they are prescribed androgen-deprivation therapy (ADT); altered sexual experience; loss of sexual function, ejaculation, and fertility; and changes in urinary function.1 The potential long-term adverse effects of treatment can be controlled effectively by providing information on sperm storage, managing erectile dysfunction, providing access to specialist continence services and psychosexual services if appropriate, and urological assessment if troublesome urinary symptoms present.
Erectile function can be improved with the use of phosphodiesterase type 5 inhibitors, vacuum devices and, if necessary, penile injections of prostaglandin E.1 Pelvic floor muscle exercises are important, not only for the restoration of continence after radical prostatectomy,1 but because they also aid the recovery of erectile function. These exercises should be combined with bladder retraining and anticholinergenic therapy if there are symptoms of overactive bladder.1
Intractable stress urinary incontinence is rare after radical prostatectomy, but can be resolved with the implantation of an artificial urinary sphincter or the use of bulking agents injected alongside the urethra, although this is not currently recommended by NICE.1
A shared-care approach is important in the management of ADT because of the metabolic effects of a low or undetectable testosterone level. Additionally, oestrogen levels also fall, increasing the risk of osteoporosis, hot flushes, and gynaecomastia.21 Side-effects of ADT include low libido or erectile dysfunction and an increased risk of developing impaired glucose tolerance, type 2 diabetes, and dyslipidaemia.22 Men receiving ADT should know their own physiological parameters, such as blood pressure, cholesterol, and glycated haemoglobin values to detect early metabolic changes leading to increased cardiovascular risk.
Androgen-deprivation therapy is commonly combined with radiotherapy and during this period it is essential that men are provided with lifestyle advice to keep their weight down. As osteoporosis is also a side-effect of ADT,23 at-risk men should be offered a dual energy X-ray absorptiometry scan to assess bone density and the need for bisphosphonate therapy. The individual risk of osteoporosis may be estimated using the FRAX® score, available at: www.sheffield.ac.uk/FRAX.
Many men with prostate cancer will be followed up every 3 to 6 months, either under a shared-care agreement or entirely in primary care. Individuals should have a personalised patient management plan that includes a triggered referral to the hospital based on PSA level or other clinical end points. The patient should be made aware of the factors that will trigger referral back to the hospital.
Local outcomes should be reported to the patient and to clinical commissioning groups (CCGs) in relation to treatment complications, functional outcomes, positive margins, volume of work, and experience of the operators.
A future challenge in the management of prostate cancer is the changing face of general practice; in 2007, women made up 40% of all doctors, 42% of GPs, and 28% of consultants.24 Research carried out in 2009 by the Royal College of Physicians, shows that the majority of doctors will be female after 2017.24 In some practices, female GPs may see women and children predominantly, and as a result may become relatively inexperienced at managing male urological problems. This includes interpretation of the DRE, and the management of male incontinence and sexual problems that commonly occur after treatment for prostate cancer. This is a problem that can be addressed via a comprehensive continuing professional development portfolio and clinical audit. Refer to Box 2, for areas of best practice to consider for audit and revalidation.
The NICE document is a comprehensive resource; however practices are inundated with guidelines every year and will only have a handful of patients with prostate cancer on their list. This makes it difficult for doctors to gain sufficient experience in managing this disease. Good lines of communication are essential as a significant proportion of clinical decision making will be performed by hospital specialists. At the end of the disease course, the GP’s role will be critical in managing the palliative care and the end-of-life package.
|Box 2: Areas of best practice to consider for audit and revalidation|
|PSA=prostate specific antigen|
Primary care has a key role in the early diagnosis of prostate cancer when the disease is localised and curable. The practice should ensure that there is access to information on the advantages and disadvantages of PSA testing and prostate biopsy.
Balanced information should be available on the various treatment options and the risk of side-effects and complications. Follow up will be shared between primary and secondary care and there should be an individualised care plan with appropriate re-referral when necessary. Attention should be paid to treatment side-effects and appropriate psychological support during follow up visits. Commissioners need to make sure that audited information on treatment outcomes is available.
An update to the NICE guideline on prostate cancer is currently in progress and publication is anticipated in November 2013.25 The Department of Health has also recommended that NICE develops a quality standard on prostate cancer.26 This will help to eliminate the regional variations that currently exist in services for prostate cancer.
|NICE Implementation tools|
NICE has developed the following tools to support implementation of Clinical Guideline 58 on Diagnosis and treatment of prostate cancer. The tools are now available to download from the NICE website: www.nice.org.uk/CG58
NICE support for commissioners
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.
NICE support for service improvement systems and audit
Clinical audit tool
Audit tools aim to assist organisations with the audit process, thereby helping to ensure that practice is in line with the NICE recommendations. They consist of audit criteria and data collection tool(s) and can be edited or adapted for local use.
Electronic audit tool
Electronic audit tools are developed to assist organisations with clinical audit and to ensure that practice is in line with the NICE recommendations.
NICE support for education and learning
The slides provide a framework for discussing the NICE guideline with a variety of audiences and can assist in local dissemination. This information does not supersede or replace the guidance itself.
This advice tool considers implementation issues that are specific to the guideline on prostate cancer.
Online educational tool
Educational modules are also available online.
NICE and British Association of Urological Surgeons implementation statement
The statement has been published to ensure that there is clarity over some of the recommendations in order to support implementation of the guideline.
- As one of the most common cancers in men, prostate cancer will have a major impact on commissioning budgets in future
- Commissioners should ensure that primary care healthcare professionals are informed of the presenting symptoms of prostate cancer and appropriate use of the PSA test
- Commissioners should ensure that:
- they are represented on local cancer network prostate cancer groups, which are involved in designing local care pathways
- patients have access to the full range of NICE-recommended therapies
- Commissioners should explore the possibility of shared-care follow up schemes for suspected or low-risk prostate cancer to reduce both patient journeys to hospital and tariff costs
- Commissioners could explore the possibility of prostate cancer specialist nurses working in the community under specialist supervision to help provide support to patients and helping them with difficult decisions about treatment
- Tariff costs for urology outpatients = Â£177 (new), Â£96 (follow up).a
- National Institute for Health and Care Excellence. Prostate cancer: diagnosis and treatment. Clinical Guideline 58. London: NICE, 2008. Available at: www.nice.org.uk/guidance/CG58
- Cancer Research UK website. Prostate cancer—UK incidence statistics. info.cancerresearchuk.org/cancerstats/types/prostate/incidence/index.htm (accessed 25 May 2012).
- National Institute for Health and Care Excellence. Prostate cancer: diagnosis and treatment. Costing report. Available at: www.nice.org.uk/guidance/CG58/CostingReport/pdf/English
- Cancer Research UK website. Prostate cancer—survival statistics. info.cancerresearchuk.org/cancerstats/types/prostate/survival/prostate-cancer-survival-statistics (accessed 25 May 2012).
- Prostate Action website. Five key facts every GP should know about prostate cancer. www.prostateaction.org.uk/news/five-key-facts-every-gp-should-know-about-prostate-cancer (accessed 25 May 2012).
- National Institute for Health and Care Excellence. Referral guidelines for suspected cancer. Clinical Guideline 27. London: NICE, 2005. Available at: www.nice.org.uk/guidance/CG027
- Burford D, Kirby M, Austoker J. Prostate cancer risk management programme. Sheffield: NHS Cancer Screening Programme, 2009.
- Department of Health publications orderline website. Prostate cancer risk management programme pack. www.orderline.dh.gov.uk/ecom_dh/public/saleproduct.jsf?catalogueCode=PROSCANRMT
- National Institute for Health and Care Excellence website. Referral for suspected cancer. www.nice.org.uk/guidance/CG/Wave0/618 (accessed 25 May 2012).
- Ahmed H, Kirkham A, Arya M et al. Is it time to consider a role for MRI before prostate biopsy? Nat Rev Clin Oncol 2009; 6 (4): 197–206.
- Medical Research Council Clinical Trials Unit website. PROMIS study. www.ctu.mrc.ac.uk/research_areas/study_details.aspx?s=126 (accessed 25 May 2012).
- National Institute for Health and Care Excellence. Transperineal template biopsy and mapping of the prostate. Interventional procedure guidance 364. London: NICE, 2010. Available at: www.nice.org.uk/nicemedia/live/12352/51312/51312.pdf
- Pesqueira D, Pereiro M, Rivas C, Comesaña E et al. Radical surgery of locally advanced prostatic cancer. Actas Eurol Esp 1995; 19 (7): 549–554.
- National Institute for Health and Care Excellence. Docetaxel for the treatment of hormone-refractory metastatic prostate cancer. Technology Appraisal 101. London: NICE 2006. Available at www.nice.org.uk/guidance/TA101
- National Institute for Health and Care Excellence website. Abiraterone for castration-resistant metastatic prostate cancer previously treated with a docetaxel-containing regimen. www.nice.org.uk/guidance/TA/Wave26/4 (accessed 28 May 2012).
- STAMPEDE website. www.stampedetrial.org (accessed 28 May 2012).
- National Institute for Health and Care Excellence. Cabazitaxel for hormone- refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen. Technology Appraisal 255. London: NICE, 2012. Available at: www.nice.org.uk/guidance/TA255
- Dy S, Asch S, Naelm A et al. Evidence-based standards for cancer pain management. J Clin Oncol 2008; 26 (23): 3879–3885.
- Gold Standards Framework website. www.goldstandardsframework.org.uk (accessed 28 May 2012).
- The Marie Curie Palliative Care Institute Liverpool website. Liverpool care pathway for the dying patient. www.mcpcil.org.uk/index.htm (accessed 28 May 2012).
- Prostate Cancer Research Institute website. Shore N, Freeland S. Side effects of androgen deprivation therapy induced by estrogen deficiency. www.prostate-cancer.org/pcricms/node/373 (accessed 6 June 2012).
- Bourke L, Chico T, Albertsen P. Cardiovascular risk in androgen suppression: underappreciated, under-researched and unresolved. Heart 2012; 98: 5345–5348.
- National Collaborating Centre for Cancer. Prostate cancer: diagnosis and treatment. Full guideline. London: NICE, 2008. Available at: www.nice.org.uk/cg58
- Elston M. Women and medicine: the future. London: Royal College of Physicians, 2009. Available at: pressrelease.rcplondon.ac.uk/Archive/2009/Women-to-become-majority-of-doctors-after-2017 (accessed 25 May 2012).
- National Institute for Health and Care Excellence website. Prostate cancer update. www.nice.org.uk/guidance/index.jsp?action=byId&o=13583 (accessed 28 May 2012).
- National Institute for Health and Care Excellence website. NICE quality standards topic library. www.nice.org.uk/guidance/qualitystandards/QualityStandardsLibrary.jsp (accessed 28 May 2012). G