The approach to treatment for advanced prostate cancer patients who have failed to respond to therapy with androgen deprivation has undergone a significant and fundamental transformation over the last 3 years, beginning with the description of the flutamide-withdrawal syndrome in 1993. This was the same year that the Cancer and Leukemia Group B Prostate Cancer Committee was created. This committee has been studying the following two important areas in advanced prostate cancer the optimal treatment and biology of androgen-independent, yet hormonally sensitive, prostate cancer; and the optimal treatment for patients with truly hormone-refractory disease. Important biologic and quality of life correlative trials will complement the clinical information gained, with the goal of providing further insight into the extremely complex biological processes involved.