The treatment of metastatic disease

Once the tumour has spread beyond the local lymph nodes and particularly if bony metastases are present, the chances of the patient dying of prostatic is 75%, regardless of age. Nonetheless, useful palliation of the disease can be readily achieved by hormonal therapy.

A number of treatments may be used to exert much the same biological effect, namely the cessation of androgen-driven growth of the cancer. The following will produce symptomatic response in about 70% of men with bone metastases, with a median response duration of 12-18 months:

♦ Surgical castration

♦ Oestrogens (no longer used because of cardiovascular toxicity)

♦ Steroidal anti-androgens such as cyproterone acetate (best avoided for long-term use because of occasional hepatotoxicity)

♦ Non-steroidal anti-androgens (flutamide, bicalutamide)

♦ Medical castration with LHRH agonists

More than 20% of patients will continue to respond for up to five years. The price for this is the toxicity of long-term castration, including:

♦ Loss of libido and potency

♦ Alteration of body form

♦ Inability to concentrate

Osteoporosis

Although initial reports on the combination of medical castration and anti-androgen therapy (Maximal Androgen Blockade or MAB) suggested a benefit over monotherapy, recent meta-analysis has shown that monotherapy and combined treatment are equivalent in efficacy. At least 30% of patients who relapse following androgen antagonist primary therapy will respond to subsequent medical or surgical castration. In addition, some patients respond to withdrawal of anti-androgens. However, the responses to second-and third-line endocrine therapy are incomplete and short-lived, and ultimately patients return with hormone refractory metastatic disease. The results of chemotherapy in this disease are poor, although responses to anthra-cyclines and the related mitoxantrone have been reported.

Radiation therapy offers useful palliation of advanced disease both in bone and soft tissue. In addition, radioactive strontium given by IV injection (150 MBq) has proved effective in relieving bone pain and delaying the progression of symptomatic bone disease.

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