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Challenges in the management of prostate cancer.

An estimated 32,000 American men will die of prostate cancer this year. Local prostate cancer may be successfully treated by radical prostatectomy or radiotherapy. Advanced cases may necessitate the use of hormonal ablation with bilateral orchiectomy, an approach that is regarded as the gold standard of therapy but not always the preferred treatment of patients. Oestrogen therapy is an alternative but is associated with side effects, such as hot flushes and gynaecomastia, which frequently lead to treatment cessation. Luteinising hormone-releasing hormone (LHRH) analogues work by initially producing a surge of androgen, followed by a down-regulation in hormone production to effect a medical castration. Various groups have studied the effects of androgen blockade administered as monotherapy and as combination therapy (LHRH analogue plus antiandrogen). The National Cancer Institute intergroup protocol 0036, which is the largest cooperative study to date of patients with advanced prostatic cancer, showed that combination therapy with leuprolide and flutamide offered greater benefit in both time to disease progression and median survival while circumventing tumour flare and its associated symptoms. Thus, combination therapy for total androgen ablation may become the new treatment standard for advanced prostatic cancer, pending further studies in the efficacy and cost-effectiveness of all available treatments.