Professor Roger Kirby reviews the latest developments in the diagnosis and treatment of prostate cancer and reflects on the benefits of NICE guidance to patients
- PSA testing is still the best available tool for the early detection of prostate cancer; however patients should be made aware of its limited specificity and sensitivity and the implications of a positive test before the assay is requested14
- Multiparametric MRI can be useful in deciding who does, or who does not, require a prostate biopsy
- Transperineal biopsies carry a lower risk of sepsis than transrectal biopsies, but require general anaesthesia and may provoke acute urinary retention
- Lower-risk localised prostate cancers can be safely managed by active surveillance
- Radical prostatectomy (often performed by keyhole surgery, with or without robotic assistance) and external beam radiotherapy are best undertaken in specialist units with a high patient throughput. There is a lamentable lack of some of the newer technologies in some areas; for example, there are still no surgical robots in use in Scotland, Northern Ireland, or Wales
- Locally advanced prostate cancers are usually best managed by a combination of androgen ablation and external beam radiotherapy
- Luteinising hormone-releasing hormone agonists are very effective in advanced prostate cancers, but carry associated risks of reduced bone density and metabolic syndrome
- After 2 years of stability after initial treatment, many patients can be safely cared for by their primary care practitioner
- Second-line treatments include chemotherapy with docetaxel and carbazitaxel, and two newer agents: abiraterone and enzalutamide
- Palliative care may require local radiotherapy to reduce bone pain and urological interventions to deal with upper and lower urinary tract complications.
PSA=prostate-specific antigen; MRI=magnetic resonance imaging
NICE Clinical Guideline 58 on Prostate cancer: diagnosis and treatment has been awarded the NICE Accreditation Mark.
This Mark identifies the most robustly produced guidance available. See evidence.nhs.uk/accreditation for further details.
P rostate cancer is the commonest solid tumour to afflict men. In the UK, around 35,000 new cases are diagnosed each year and more than 10,000 individuals will die from the disease in 2013.
Current NICE prostate cancer clinical guidance
NICE published its first clinical guideline on the diagnosis and management of prostate cancer in 2008 (NICE Clinical Guideline (CG) 58, see www.nice.org.uk/guidance/CG58). 1
At first, this guidance proved controversial, especially the recommendation that ‘active surveillance’ should be discussed as a management option for all patients with a low- or intermediate-risk prostate cancer.1
Looking back from a current perspective, however, it is increasingly accepted by urologists and oncologists that active surveillance is a safe and effective option for the management of certain men with localised prostate cancer.2,3 Indeed, it would appear that only around one-third of men with lower risk prostate cancer (that is prostate specific antigen [PSA)]<10 ng/ml and Gleason score of 3+3=6 in less than 50% of biopsy cores) eventually require surgical intervention or radiotherapy. 4
It seems probable that the 2008 guidance provided in NICE CG58 has been responsible for a significant reduction in the number of men over-treated with either surgery or radiotherapy for localised prostate cancers that in fact posed little threat to them over their natural lifespan.
There are several other important recommendations from NICE CG58 that have been influential and widely implemented, for example that:
- patient management should be based on joint decision-making by a multidisciplinary team (MDT), taking into account individual patient preferences
- at least 10 cores should be taken at the time of prostate biopsy to reduce the risk of a missed diagnosis
- after at least 2 years’ follow up, patients whose PSA is stable after treatment may be referred back to their primary care practitioner.1
The last of these recommendations, of course, assumes that the primary care practitioner has sufficient interest and knowledge to continue follow up and re-refer the patient if problems such as a rising PSA, or bladder outflow or ureteric obstruction, occur. The key points box overleaf provides some important messages for primary care practitioners dealing with the very many men who have been diagnosed with, treated for, and are surviving prostate cancer.
The role of primary care
Primary care practitioners have an important role in the diagnosis and follow up of men with prostate cancer. The diagnosis still largely relies on the admittedly imperfect PSA test, which has been shown to reduce mortality from prostate cancer by more than 20%, but at the expense of the over-diagnosis of a proportion of clinically insignificant cancers.5 Men in whom prostate cancer is suspected will usually need referral for MRI and biopsy confirmation. A significant proportion can be managed by active surveillance. Follow-up after treatment is also largely PSA-based; a progressive rise in this marker in spite of androgen ablation therapy indicates the development of castration-resistant prostate cancer (CRPC). The barrier to the NICE recommendation1 that more men with prostate cancer should be followed up in primary care has often been the reluctance of urologists to discharge the patients from secondary care clinics.
Updates are awaited to NICE prostate cancer clinical guidance
A revised prostate cancer guideline is due for publication in early 2014 (see www.nice.org.uk/guidance/CG/Wave0/637) and NICE is currently consulting with the various stakeholders (including clinicians, patients, and the various prostate cancer charities).6 There have been a number of important evidenced-based developments during the past 5 to 6 years that will all need to be considered, including developments in:
- biopsy route
- drug treatments.
Possibly the most important development is the recent recognition that multiparametric magnetic resonance imaging (MRI), especially using the newer 3 Tesla MRI machines,7 can identify and target the higher risk cancers that constitute a threat to life, and reduce the number of unnecessary biopsies.8 As the number of serious post-biopsy infections is rising, and there is an increase in the prevalence of multiresistant Escherichia coli (E. coli), this possible reduction in unnecessary biopsies should be viewed as a positive development.9
Another important trend is the move from transrectal to transperineal as the chosen route for prostate biopsy, not only to improve yield, but also as a means of avoiding the risk of post-biopsy sepsis.10
Two new and important treatment options have received marketing authorisation for use in CRPC:
Both of these drugs have been shown to improve survival of men with CRPC: abiraterone in both the pre- and post-chemotherapy situations, and enzalutamide at present only in the post-chemotherapy setting, although this seems likely to change soon as new trial data are anticipated shortly. Abiraterone has to be administered in combination with a low dose of prednisone; in contrast enzalutamide can be administered without prednisone. These pharmacological developments, together with a number of other advances, are now significantly improving the prospects for men with advanced prostate cancer.13
This is a rapidly changing field and new data are emerging frequently, for example on the pre-chemotherapy value of abiraterone.14 NICE TA259 has evaluated the use of abiraterone (June 2012, see publications.nice.org.uk/abiraterone-for-castration-resistant-metastatic-prostate-cancer-previously-treated-with-a-ta259). A NICE technology appraisal for enzalutamide is currently in development (see www.nice.org.uk/guidance/TA/WaveR/165).
Despite some initial scepticism,15 the 2008 NICE prostate cancer guideline (CG58) has stood the test of time and is now generally accepted by practitioners as being useful.16 In fact, there is little doubt (in the author’s opinion) that the early recommendation of active surveillance as a management strategy for lower risk prostate tumours has most likely saved a considerable number of men from unnecessary surgery and radiotherapy. Now is certainly a good time for the new, revised guideline to be developed. I am optimistic that, when the updated NICE guidance is published early next year, it will further help to standardise the management of the over 35,000 UK individuals who are predicted to be diagnosed annually with prostate cancer—the second most common cause of cancer-related deaths in men.17
- Prostate cancer is one of the four most common cancers, where elements of care are commissioned by CCGs
- This situation is complicated, however, as all radiotherapy, chemotherapy, and specialist (robotic) surgery is commissioned by NHS England and urology outpatient services, but biopsies and non-robotic surgery are commissioned by CCGs
- This complexity requires both CCG and specialist commissioners to meet with local specialist services and describe clear local pathways for care, ensuring all NICE guidance is met
- CCGs should work with local practices to ensure they have robust follow-up systems for managing patients with stable prostate cancer who have been discharged from secondary care
- Managing these patients could be described through a Local Enhanced Service with clear quality and audit requirements and which reimburses practices for the extra work (but with money freed up from fewer urological follow-up appointments)
- GP follow up can be co-ordinated by a central database (PSA tracker), where records of all patients discharged to general practice are held; a specialist nurse can ensure all of these patients have the required tests and follow up
- Tariff costs for urology outpatients: £129 (new), £71 follow up.a
CCGs=clinical commissioning groups; PSA=prostate-specific antigen
- NICE. Prostate cancer: diagnosis and treatment. Clinical Guideline 58. London: NICE, 2008. Available at: publications.nice.org.uk/prostate-cancer-cg58
- Lees K, Durve M, Parker C. Active surveillance in prostate cancer: patient selection and triggers for intervention. Curr Opin Urol 2012; 22 (3): 210–215.
- Klotz L. Active surveillance for favorable-risk prostate cancer: background, patient selection, triggers for intervention, and outcomes. Curr Urol Rep 2012; 13 (2): 153–159.
- Klotz L. Active surveillance not only reduces morbidity, it saves lives. Oncology (Williston Park). 2013; 27 (6): 522, 593.
- Schröder F, Hugosson J, Roobol M et al. Prostate-cancer mortality at 11 years of follow-up. N Engl J Med 2012: 366 (11): 981–990.
- NICE website. Prostate cancer update. See www.nice.org.uk/guidance/CG/Wave0/637 (accessed 20 August 2013).
- 3T Imaging website. See www.3timaging.com (accessed 20 August 2013).
- Vargas H, Akin O, Afaq A et al. Magnetic resonance imaging for predicting prostate biopsy findings in patients considered for active surveillance of clinically low risk prostate cancer. J Urol 2012; 188 (5): 1732–1738.
- Patel U, Dasgupta P, Amoroso P et al. Infection after transrectal ultrasonography-guided prostate biopsy: increased relative risks after recent international travel or antibiotic use. BJU Int 2012; 109 (12): 1781–1785.
- Kirby R, Patel U, Challacombe B, Dasgupta P. Changing paradigms in the investigation of an elevated PSA level. BJU Int 2013; 112 (3): 283–285.
- de Bono J, Logothetis, C, Molina J et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011; 364 (21): 1995–2005.
- Scher H, Fizazi K, Saad F et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 2012: 367 (13): 1187–1197.
- Kirby R Fitzpatrick J. Improved survival prospects for patients with castration-resistant prostate cancer. BJU Int 2011; 107 (5): 697–700.
- Ryan C, Smith M, de Bono J et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 2013; 368 (2): 138–148.
- Wong L, Johnston R, Sharma N et al. General application of the National Institute for Health and Clinical Excellence (NICE) guidance for active surveillance for men with prostate cancer is not appropriate in unscreened populations. BJU Int 2012; 110 (1): 24–27.
- Payne H, Clarke N, Huddart R et al. Nasty or nice? Findings from a UK survey to evaluate the impact of the National Institute for Health and Clinical Excellence (NICE) clinical guidelines on the management of prostate cancer. Clin Oncol (R Coll Radiol) 2013; 25 (3): 178–189.
- NHS Cancer Screening Programme. Advising men about the PSA test for prostate cancer. Prostate Cancer Risk Management Programme, 2009. Available at: www.cancerscreening.nhs.uk/prostate/prostate-patient-info-sheet.pdfG