Mr Matthew Jefferies (left) and Professor Howard Kynaston explain changes and new options in the updated NICE guideline on the diagnosis and treatment of prostate cancer
P rostate cancer is now recognised as one of the most important health issues facing the male population. Approximately 40,000 men are diagnosed with prostate cancer every year in the UK,1 and the number of diagnoses continues to rise. While it is already the most common cancer in UK males, prostate cancer is predicted to become the most commonly diagnosed cancer of all between both sexes by 2030.2 This is thought to be as a result of the ageing population and the increased use of prostate-specific antigen (PSA) testing.
Prostate cancer is strongly associated with increasing age; 75% of cases occur in men aged over 65 years with only 1% occurring in men younger than 50 years.1 Other risk factors include family history and black African-Caribbean ethnicity.3 Germline mutations in the BRCA1 and BRCA2 genes, which are linked to familial breast cancer, have also been associated with a higher risk of prostate cancer. 4,5
Traditionally, specialist clinical and surgical oncologists manage prostate cancer. However, more patients are being seen in primary care settings as the number of men diagnosed and treated increases. This includes follow-up appointments for men on a watchful-waiting regimen or an active surveillance protocol, or for men who present with side-effects or complications related to their treatment.
The NICE guideline on the diagnosis and treatment of prostate cancer, first published in February 2008,6 was updated in January 2014 and published as Clinical Guideline (CG) 175 (see www.nice.org.uk/guidance/CG175 and Box 1).7 Although many areas of the original guideline are unchanged, as there is little or no new evidence, some aspects have been completely rewritten. The research recommendations for areas that lacked evidence can be used as the basis for future work.
This article covers the key changes and recommendations in NICE CG175 that are relevant to both primary and secondary care.
|Box 1: NICE Accreditation Mark|
|NICE Clinical Guideline 175 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.
Diagnosis and staging
The pathway for diagnosing and staging men with prostate cancer is shown in Figure 1.8 Typically, men with suspected prostate cancer are referred if they have a raised PSA. The PSA test is usually performed in primary care in accordance with the reference ranges set out by the UK Prostate Cancer Risk Management Programme.9 NICE CG175 continues to recommend that, in addition to the PSA level, digital rectal examination (DRE) findings, co-morbidities, and risk factors should be taken into account prior to considering prostate biopsy.7
Multiparametric magnetic resonance imaging
With advances in imaging technology, NICE CG175 update has provided guidance for the use of multiparametric magnetic resonance imaging (MRI) (using T2- and diffusion-weight imaging). A multiparametric MRI should be considered for men with:7
- a negative transrectal ultrasound 10–12 core biopsy to determine whether another biopsy is needed
- histologically proven prostate cancer if knowledge of the T or N stage could affect management.
Risk stratification for localised and locally advanced prostate cancer
Several factors have been shown to predict the risk of recurrence after treatment of localised prostate cancer. These include the Gleason score, the serum PSA level, and the clinical T-stage. These predictive factors are used to classify men with localised prostate cancer into a risk group (see Table 1); risk stratification is usually determined by the urological cancer multidisciplinary team (MDT) prior to deciding on treatment.
|Level of risk||PSA||Gleason score||Clinical Stage|
|Low risk||<10 ng/ml||and||≤6||and||T1–T2a|
|Intermediate risk||10–20 ng/ml||or||7||or||T2b|
|High risk*||>20 ng/ml||or||8–10||or||≥T2c|
Low-risk localised prostate cancer
Prostate cancer may follow an aggressive course, similar to that of other cancers. However, many prostate cancers are slow-growing or ‘indolent’ and will have no impact on health, even without treatment. In the PSA era, more asymptomatic men are being diagnosed with low-risk localised disease, so the challenge is to identify which individuals will have disease progression and benefit from radical treatment. This uncertainty and the indolent nature of low-risk localised prostate cancer make it very difficult when deciding on a treatment strategy. Specialist surgical and clinical oncologists should ensure that men are provided with details of each treatment option, explaining their risks and benefits without the influence of any personal bias.
The management options for low-risk localised prostate cancer include:7
- active surveillance
- radical prostatectomy
- radical external-beam radiotherapy (EBRT)
- watchful waiting.
A new recommendation for the 2014 guideline update is that men with low-risk localised prostate cancer who are eligible for curative treatments should also be offered active surveillance.7 The objective of active surveillance is to avoid unnecessary treatment of men with indolent cancers, by only treating those with cancer that shows early signs of progression and may be life threatening. Importantly, men enrolled into an active-surveillance programme should be suitable for radical surgery or radiotherapy if their disease progresses. An example of an active-surveillance protocol is shown in Table 2.
Watchful waiting differs from active surveillance in that it involves attempting to avoid treatment and its associated side-effects, unless symptoms of progressive disease develop. This is usually offered to older men or to those with significant co-morbidities. If disease progression develops, treatment is usually with palliative androgen-deprivation therapy (ADT).10
|At enrolment in active surveillance||Multiparametric MRI if not previously performed|
|Year 1 of active surveillance||Every 3–4 months: measure PSA† Throughout active surveillance: monitor PSA kinetics‡ Every 6–12 months: DRE§ At 12 months: prostate rebiopsy|
|Years 2–4 of active surveillance||Every 3–6 months: measure PSA† Throughout active surveillance: monitor PSA kinetics‡ Every 6–12 months: DRE§|
|Year 5 and every year thereafter until active surveillance ends||Every 3–6 months: measure PSA† Throughout active surveillance: monitor PSA kinetics‡ Every 12 months: DRE§|
Intermediate and high-risk localised/locally advanced prostate cancer
The mainstay of treatment for intermediate- and high-risk localised disease is either radical prostatectomy or radical EBRT. The updated guideline also recommends:7
- considering active surveillance for men with intermediate-risk localised prostate cancer who do not wish to have immediate radical treatment
- offering a combination of radical radiotherapy and ADT, rather than radical radiotherapy or ADT alone, for men with intermediate- and high-risk localised prostate cancer.
Evidence suggests that combined hormone therapy and EBRT is associated with a longer overall survival and metastasis-free survival rate in patients with local or locally advanced prostate cancer.11
The guideline development group suggested areas for further research, including the use of high-dose brachytherapy in combination with EBRT for men with intermediate- and high-risk localised prostate cancer. Brachytherapy is able to deliver a higher dose of radiation to the prostate when compared with EBRT as it does not have to traverse normal tissue to reach the prostate. Brachytherapy does not deliver any significant radiation outside the prostate capsule, which may be a significant limitation in high-risk or locally advanced disease where extracapsular extension is more prevalent. Hence, a combination of brachytherapy and EBRT may be optimal.7
Metastatic prostate cancer
The mainstay of the management of metastatic disease is the use of ADT in the form of luteinising hormone-releasing hormone agonists (LHRHa) or androgen blockade (anti-androgens). Long-term use of hormone therapy can have undesired effects such as osteoporosis, hot flushes, fatigue, and erectile dysfunction.7 Consequently, the 2014 update has recommended considering intermittent therapy for men on long-term ADT. Men receiving intermittent therapy should have their PSA measured every 3 months and restart ADT if >10 ng/ml or if there is symptomatic progression.7
The complications associated with treatment for prostate cancer, and in particular those related to surgery, radiotherapy, and ADT, can have a significant effect on a man’s quality of life. It is essential that all healthcare professionals who are involved in managing prostate cancer know of and understand these side-effects so that they can be identified, treated, and the patient counselled appropriately. Figure 2 highlights how the complications of treatment should be managed, as recommended by the updated 2014 guideline.8
Impact on primary care
Although the majority of the risk stratification and management decisions associated with prostate cancer are made by specialists in the urological cancer MDT, GPs and other healthcare professionals in primary care will experience greater responsibility and workload as a result of the updated NICE guideline. Secondary care alone lacks the capacity to cope with the increasing number of patients, but primary care lacks the expertise to manage treatment without support. Shared care between the primary and secondary sectors could offer a solution to the problem.
General practitioners could be responsible for:
- checking PSA levels and reviewing symptoms that may indicate disease progression:
- as part of a watchful waiting regimen or active surveillance protocol or
- for men who have stable disease
- 2 years after radical treatment
- advising the specialist clinical or surgical oncologists of signs of clinical progression or deterioration
- prescribing ADT therapy
- managing the side-effects of treatment such as erectile dysfunction or osteoporosis
- providing psychological support for men and their families
- referring patients to specialist community services such as continence specialist nurses, pain teams, or palliative care teams.
Some useful patient information on prostate cancer can be found on the websites for Prostate Cancer UK (see prostatecanceruk.org) and Macmillan Cancer Support (see www.macmillan.org.uk/Cancerinformation/Cancertypes/Prostate/Prostatecancer.aspx#).
Specialist surgical and clinical oncologists’ support for GPs could include:
- giving access to cancer MDT protocols on watchful waiting and active surveillance
- developing protocols for drug prescribing such as LHRHa
- ensuring rapid access to clinics or the cancer MDT for patients with progressive disease to ensure there is no delay in treatment
- providing protocols for the management of the side-effects of treatment such as osteoporosis, hot flushes, and erectile dysfunction.
Limitations of primary care
Evidently, it would be very difficult to implement a follow-up strategy and recommendations for patients with high-risk disease, or after recent radical treatment, in a primary care setting, as intensive surveillance for disease progression and the effects of treatment is required.
Other patients who are unsuitable for follow up in primary care and who will require specialist care include men who:
- have unstable disease
- are experiencing significant treatment side-effects
- have an increased risk of complications, such as ureteric obstruction or spinal cord compression.
The incidence of prostate cancer is increasing. The updated NICE guideline on the diagnosis and treatment of prostate cancer highlights the role of active surveillance and multiparametric MRI in low-risk localised disease. For men with intermediate- or high-risk localised disease, a combination of surgery or radiotherapy with hormones is now the mainstay of treatment. This guideline clearly underlines how the complications associated with these treatments should be managed in order to reduce morbidity and improve quality of life. General practitioners will have an increasingly active role in supporting men with prostate cancer.
- For prostate cancer:
- CCGs are responsible for commissioning outpatient care, most surgical and diagnostic procedures, and hormone therapy
- NHS England is responsible for commissioning robotic surgery, radiotherapy, and chemotherapy
- Although NICE CG175 recommends the use of multi-parametric MRI after biopsy, many specialists are now using this as an alternative to biopsy and CCGs will need to agree local pathways to define its use and agree tariff prices
- Commissioners should look to forge local shared-care protocols between primary and secondary care for active surveillance and watchful waiting. Such schemes are likely to reduce follow-up outpatient costs but investment may be needed for:
- software support (such as the PSA tracker system) to ensure effective recall
- local enhanced services to fund general practice for the extra responsibilities
- CCGs should also look to develop specialist nurse roles to support patients diagnosed with cancer in â€˜survivorship schemesâ€™, and also to help educate general practitioners
- Tariff costs for urology outpatients: £129 (new), £71 (follow up).a
CCG=clinical commissioning group; CG=clinical guideline; MRI=magnetic resonance imaging; PSA=prostate-specific antigen
- Cancer Research UK website. Prostate cancer incidence statistics.www.cancerresearchuk.org/cancer-info/cancerstats/types/prostate/incidence/ (accessed 3 February 2014).
- Mistry M, Parkin D, Ahmad A, Sasieni P. Cancer incidence in the United Kingdom: projections to the year 2030. Br J Cancer 2011; 105 (11): 1795–1803.
- Cancer Research UK website. Prostate cancer risk factors. www.cancerresearchuk.org/cancer-info/cancerstats/types/prostate/riskfactors/ (accessed 3 February 2014).
- Kote-Jarai Z, Leongamornlert D, Saunders E et al. BRCA2 is a moderate penetrating gene contributing to young-onset prostate cancer: implications for genetic testing in prostate cancer patients. Br J Cancer 2011; 105 (8): 1230–1234.
- Leongamornlert D, Mahmud N, Tymrakiewicz M et al. Germline BRCA1 mutations increase prostate cancer risk. Br J Cancer 2012; 106 (10): 1697–1701.
- NICE. Prostate cancer: diagnosis and treatment. Clinical Guideline 58. NICE, 2008.
- NICE. Prostate cancer: diagnosis and treatment. Clinical Guideline 175. NICE, 2014. Available at: www.nice.org.uk/CG175
- National Collaborating Centre for Cancer. Prostate cancer: diagnosis and treatment. London, 2014. Full guideline. Available at: www.nice.org.uk/nicemedia/live/14348/66232/66232.pdf
- Burford D, Kirby M, Austoker J. Prostate cancer risk management programme. Guide no 2. Information for primary care: PSA testing in asymptomatic men. Evidence document. NHS Cancer Screening Programmes, 2010. Available at: www.cancerscreening.nhs.uk/prostate/pcrmp-guide-2.html
- Lu-Yao G, Albertsen P, Moore D et al. Outcomes of localized prostate cancer following conservative management. JAMA 2009; 302 (11): 1202–1209.
- Kumar S, Shelley M, Harrison C et al. Neo-adjuvant and adjuvant hormone therapy for localized and locally advanced prostate cancer. Cochrane Database Syst Rev 2006; (4): CD006019.
- Prostate Cancer UK website. prostatecanceruk.org (accessed 13 February 2014).
- Macmillan Cancer Support website. www.macmillan.org.uk/Cancerinformation/Cancertypes/Prostate/Prostatecancer.aspx# (accessed 13 February 2014). G