Contemporary hormonal management of advanced prostate cancer

The traditional definition of "advanced" prostate cancer includes only patients with widespread osteoblastic or soft-tissue metastases (clinical or pathologic stage T any N any M1; or stage D2). Current evidence indicates that this definition should be broadened. Because many patients with T3 disease or local lymph node metastases progress to distant metastases, the concept of advanced prostate cancer should also include stages C and D1 (T3, T4, and any T N1). Furthermore, based on pretreatment prostate-specific antigen (PSA) levels, many men treated for clinically localized disease will progress rapidly and, depending on their age and general health, should be included in the advanced-disease category. Also, using prognostic marker modeling with PSA, tumor grade, and other factors, recurrences can be predicted even earlier in many cases. This may be particularly significant in light of recent clinical data indicating that early androgen ablation therapy delays disease progression and improves survival in patients with advanced (M0 or M1) disease. The luteinizing hormone-releasing hormone (LHRH) agonists have become the preferred method of androgen ablation in patients with advanced prostate cancer. Use of an LHRH agonist, alone or combined with an antiandrogen, is more acceptable to many patients than orchiectomy and lacks the potential cardiotoxicity associated with estrogens. Combined hormonal therapy remains controversial but may provide a modest survival benefit, especially in men with minimal metastatic disease. Intermittent hormonal therapy has great appeal, particularly because of the potentially deleterious effects of long-term hormonal therapy; however, its efficacy has yet to be proven.