Arguments for the long-term use of combined androgen blockade.

From what is known about the testicular and adrenal origins of testosterone, and the testosterone dependency of prostate cancer, treatment with combined androgen blockade (CAB) by castration plus an antiandrogen was expected to be beneficial to patients. A number of early studies verified this hypothesis, but the findings needed to be confirmed in large, randomized, prospective studies. Modest but significant benefits of CAB were seen when treatment with leuprorelin plus flutamide was compared with leuprorelin alone. Of note was the increased benefit from CAB seen in patients with minimal metastatic prostate cancer, a finding that needed to be confirmed. A study comparing orchidectomy plus nilutamide with orchidectomy alone showed significant benefits of CAB in terms of time to progression and overall survival. However, a recent major NCI study revealed no benefits for CAB with respect to survival, even for patients with minimal metastatic disease. Results from other clinical studies have been conflicting, perhaps because of the method of castration or differences in antiandrogen used. Before the question of whether CAB significantly benefits patients can be fully answered, a clearer understanding of the interactions between antiandrogens, luteinizing hormone-releasing hormone agonists and receptors, and of the response of prostate cancer to these, is needed.