Abstract

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• In the treatment of advanced prostate cancer, androgen ablation has proven to be the cornerstone. Several important questions about its use, however, remain unanswered. The first question is whether androgen ablation should be started at the time of diagnosis, or when symptoms arise. Although previous evidence had suggested no benefit to early therapy, a recent large trial of patients has shown clear benefit. Patients with locally advanced and asymptomatic metastatic disease were randomly assigned to early treatment, or treatment started at signs of progression: the early treatment group showed benefit in time to progression, incidence of severe complications, and time to death. The other major unresolved issue is the type of androgen ablation to be used. Maximal androgen blockade (MAB) has been shown to increase the survival of patients with metastatic disease in a least two large, well-conducted trial, although other trials have contradicted this finding. A recent meta-analysis of 22 MAB trials containing more than 5000 patients has suggested that MAB does not prolong life. A large trial by the National Cancer Institute (NCI) NCI INT-0105, from which preliminary results are now available, has shown that castration and an antiandrogen is no better than castration alone in terms of time to progression and survival. This trial, furthermore, did not find that MAB was superior in low-volume, good-performance status patients. Androgen ablation is not a cure for advanced prostate cancer, but it does provide excellent palliation. New treatment regimens, and new studies, are needed to optimize treatment for these men.