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NICE has updated its 2008 clinical recommendations on the management of prostate cancer. Here is a look at the new guideline.

Prostate cancer is the commonest cancer in men in the UK – responsible for around one-quarter of all male cancer diagnoses – and the second commonest cause of cancer death in men, after lung cancer.

Diagnosis is highest in men aged 65 to 79 years, but some 25 per cent of cases occur in younger men. Men of black African-Caribbean origin are three times more likely to develop the disease than white Caucasian men.

“[Prostate cancer] can be very slow growing and whilst many men will have a cancer that won’t cause them any harm in their lifetime, nearly 10,000 men still die every year in England and Wales,” says Professor Mark Baker, director of the centre for clinical practice at NICE.

The new guideline points out that, with the introduction of prostate-specific antigen (PSA) testing, nowadays most prostate cancer is either localised or locally advanced at diagnosis (i.e. with no evidence of spread beyond the pelvis).

NICE emphasises the importance of giving men information on all relevant treatment options. There are four main treatments:

• Active surveillance
• Radical surgery (prostatectomy)
• Radical radiotherapy
• Hormone therapy.

Hormone therapy (androgen deprivation or anti-androgens) is the usual first treatment for metastatic prostate cancer and is also increasingly being used for locally advanced, non-metastatic disease. The guideline notes that most men with locally advanced cancer will receive hormone therapy as at least part of their treatment.

The guideline has a new protocol for men who choose active surveillance

Active surveillance

Active surveillance is a way of monitoring slow-growing prostate cancers that might never progress or cause any symptoms. It is curative in intent. The idea is to avoid unnecessary treatment, which can be associated with significant short- and long-term complications, until disease progression occurs (or the patient requests treatment).

“Active surveillance involves regular check-ups to see if and how the cancer is developing, rather than immediate radical treatment,” says Professor Baker.

Active surveillance is not the same as traditional “watchful waiting”, which is palliative, not curative, and aims to avoid all treatment for as long as possible. Watchful waiting is an option for men with localised cancer who are either not suitable for, or do not ever wish to receive, curative treatment. If symptoms of progressive disease develop, patients are usually treated with hormonal therapy. This approach is most often offered to older men, or men with significant co-morbidities, in whom prostate cancer may never cause problems.

The guideline has a new protocol for men who choose active surveillance. This includes measuring prostate-specific antigen (PSA) levels every three to four months in the first year of surveillance, and then at increasing intervals if there is no evidence of disease progression.

NICE suggests that active surveillance should be offered as an option to men with low-risk localised prostate cancer for whom radical prostatectomy or radiotherapy is suitable. Radical treatment is then offered to men undergoing surveillance who show evidence of disease progression. Active surveillance should also be considered, NICE says, for men with intermediate-risk, localised cancer, who do not wish to have immediate radical treatment. It is not an option for men with high-risk localised disease.

Another new recommendation is that men with intermediate- and high-risk localised cancer should be offered a combination of radical radiotherapy and androgen deprivation therapy, rather than either of these treatments on their own.

For men with metastatic disease receiving long-term androgen deprivation therapy, the guideline points out that intermittent therapy can be considered. There is no evidence of survival difference between intermittent and continuous hormone therapy, and some limited evidence for reduction in adverse events and improved quality of life with intermittent treatment. In such cases, treatment restarts if there is symptomatic progression or a specific rise in PSA.

Key points

Old and young

Diagnosis is highest in men aged 65 to 79 years, but 25 per cent of prostate cancer cases occur in younger men

Adverse effects

There are new recommend- ations on managing the adverse effects of hormone therapy for prostate cancer

Fracture risk

Men receiving long-term androgen deprivation therapy have an increased risk of fracture

Managing adverse effects

The guideline emphasises the importance of warning men about the likely adverse effects from radical treatment of prostate cancer. The major ones, which are common, long-lasting and can seriously affect quality of life, are sexual dysfunction, urinary incontinence and radiation-induced enteropathy. Men should have access to specialised services for help with these problems, NICE says.

New recommendations are also given on managing the adverse effects of hormone therapy. Androgen deprivation decreases testosterone levels and this can lead to adverse effects, including cardiovascular morbidity/mortality, hot flushes, sexual dysfunction, osteoporosis and fatigue. Anti-androgen therapy is less likely to result in sexual dysfunction and/or lethargy, but commonly causes breast enlargement (gynaecomastia) and breast pain.

For troublesome hot flushes, medroxyprogesterone should be offered. If contraindicated, alternatives are cyproterone acetate or megestrol acetate. Men should be advised there is no good evidence for complementary therapies for hot flushes, NICE says.

Bone health also needs to be considered as men receiving long-term androgen deprivation therapy have an increased fracture risk. Bisphosphonates or, if these drugs are contra-indicated, denosumab should be offered to patients who have osteoporosis.

Fatigue is a recognised side-effect of therapy and NICE recommends supervised exercise to reduce fatigue and improve quality of life. For the future, NICE emphasises that more research is needed on prognostic indicators, to help differentiate between men who may die with prostate cancer and those who may die from prostate cancer:

“The greatest uncertainties in managing prostate cancer are around the identification of which cancers are of clinical significance and over the choice of radical treatment...With the diagnosis of prostate cancer being made more frequently in asymptomatic men, it is of growing importance to know which of these men are likely to benefit from aggressive treatment.”

Several new drugs have recently been licensed for hormone-relapsed metastatic disease. These drugs are not specifically discussed in the guideline but are dealt with separately in NICE technology appraisals. 

_Reference

_{Prostate cancer: diagnosis and treatment. NICE clinical guideline 175; January 2014.}