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How should we manage prostate cancer?

Oncology specialists Dr Heather Payne and Dr Omi Parikh describe how treatments are targeted to individuals with prostate cancer

Oncology specialists Dr Heather Payne and Dr Omi Parikh describe how treatments are targeted to individuals with prostate cancer

In the UK prostate cancer is now the most common form of cancer in men, with a lifetime risk of one in 14 for all men. In 2002, 31,900 men were diagnosed, accounting for 23% of all new male cancers. Although the incidence of prostate cancer has increased in the past 20 years, mortality (10,000 per year in the UK) has remained stable because of advances in diagnosis and treatment.

Prostate specific antigen (PSA), tumour, node and metastases (TNM) staging and Gleason score (see box below) are all used to help categorise prostate cancer. There is no clear consensus on the optimum management of different stages of prostate cancer, and so therapy has to be individualised with discussions involving primary and secondary healthcare teams depending on age, lifestyle, general health and the man's treatment preferences. Patients' direct involvement in treatment decisions has been shown to correlate with the level of satisfaction of treatment. With this complex picture, guidelines are needed. The British Uro-oncology Group (BUG), the British Association of Urological Surgeons (BAUS) and the British Prostate Group (BPG) have combined to produce algorithm-based guidance for multidisciplinary teams. These management algorithms are summarised here

Evidence-based guidelines

The BUG/BAUS/BPG guidelines are based on the evidence currently available and are designed to give a list of options to discuss with each patient.

The guidelines are centred on three algorithms covering the management of different stages of prostate cancer:

• localised • locally advanced • advanced or metastatic.

Localised disease

Localised disease can be further classified into:

• high risk (Gleason grade 8 or more, PSA 20ng/ml or more)

• intermediate risk (Gleason grade 7 and/or PSA 10-20ng/ml)

• low risk (Gleason grade 6 or less, PSA 10ng/ml or below).

Treatment options for low and intermediate risk include:

• active surveillance • radical prostatectomy • external beam radiotherapy (EBRT) • low-dose rate (LDR) brachytherapy, perhaps with hormone therapy.

However, high-risk disease is treated as locally advanced disease because these factors also indicate a high risk of microscopic metastases, often requiring combined modality therapy.

Active surveillance

Active surveillance may be suitable for some men with low-risk localised disease. It is important here to distinguish between watchful waiting, which involves relatively lax observation with late, palliative treatment for those who develop symptoms, and active surveillance, which involves close monitoring (three-monthly PSA test, re-imaging and re-biopsy at 12 to 18 months) and early, radical treatment at the first signs of progression.

For men with low or intermediate-risk localised prostate cancer, who require radical treatment, there is no clear evidence to show superiority of either radical prostatectomy, or EBRT or brachytherapy.

Radical prostatectomy

This procedure is most effective in those under 70 years of age.

EBRT

Conventional EBRT is effective in localised prostate cancer but results are highly dependent on the stage of disease and other risk factors. Neo-adjuvant hormone therapy reduces prostate volume by 30-40%, which may allow a reduction in radiotherapy volume and an additive effect on cell kill.

LDR brachytherapy

This technique involves implantation of permanent radioactive iodine or palladium seeds into the prostate under ultrasound guidance. It is shown to be as effective as EBRT or radical prostatectomy for patients with localised disease (up to T2a) with a Gleason grade of 6 or below and a PSA of 10ng/ml or below.

Locally advanced disease

Treatment options include:

• EBRT with neo-adjuvant, concomitant and adjuvant hormone therapy

• hormone therapy alone

• occasionally watchful waiting.

As with localised disease, this needs careful discussion with primary and secondary care healthcare teams regarding the decision-making process. In patients with an unfavourable prognosis, higher doses of radiotherapy using three-dimensional conformal radiotherapy, intensity-modulated radiotherapy or a high dose-rate brachytherapy boost in combination with EBRT can improve local control. There is strong evidence for the use of adjuvant treatment with goserelin (EORTC 22863, RTOG 85-31, RTOG 92-02) and bicalutamide (Early Prostate Cancer Study) in combination with radiotherapy for improved overall survival. If hormone therapy is to be used alone, then immediate hormone treatment is more effective in reducing distant progression and mortality than deferred hormone treatment.

Advanced metastatic disease

Primary treatment in advanced disease is androgen deprivation, typically with an LHRH analogue.

Some patients who fail on initial hormone therapy will respond to second- or third-line hormone therapy, such as the addition of an anti-androgen to achieve 'combined androgen blockade' (CAB), diethylstilboestrol or steroids. However, many patients with metastatic cancer will eventually develop hormone refractory disease. For patients with hormone refractory cancer, chemotherapy, strontium and bisphosphonates are possible options. Strontium for palliation may have benefits in pain control or prevention of new sites of bone pain. A study with zoledronic acid, a bisphosphonate, has shown a reduction in the incidence of skeletal-related events. All patients with advanced prostate cancer should be referred for palliative care.

Dr Heather Payne is a consultant in clinical oncology at University College Hospital, London

Competing interests Dr Payne has been paid for lectures and contributions to opinion leader programmes by Astra Zeneca

Dr Omi Parikh is a specialist senior registrar in clinical oncology at University College Hospital, London

Competing interests None declared

TNM staging and gleason score

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