Hormonal therapy for metastatic prostate cancer: issues of timing and total androgen ablation

This review summarize results of hormonal management in patients with metastatic prostate cancer in terms of both timing and amount of androgen blockade. The standard of delayed hormonal therapy resulted from data of the Veterans Administration Cooperative Urologic Research Group showing high toxicity in patients treated with estrogen therapy. Reanalysis of those data using cancer-specific deaths showed improved cancer-specific survival with early hormonal therapy. A large and growing body of clinical data also suggests a superior benefit to early hormonal therapy. The concept of total androgen (adrenal and testicular) ablation was supported by reports that show a survival advantage using a combined blockade over luteinizing hormone-releasing hormone agonist alone. A National Cancer Institute study showed particularly impressive disease-free and overall survival in a subset of patients with low volume disease and good performance status. However, caution should be exercise in view of differing Canadian and European data. This review provides guidelines for treatment, but ultimately the timing and amount of androgen deprivation must be tailored to the individual patient. Ongoing and future prospective studies hold the promise of answers to these difficult and unresolved questions.