Benign Prostatic Hyperplasia (BPH) is the most prevalent of all pathologic entities in aging males. It is estimated that 50% of men 60 years of age and 88% of men 80 years old are affected by BPH. For unknown reasons, however, only about half of men with microscopic BPH will go on to develop macroscopic disease, and only about half of these patients will actually develop the clinical syndrome. Data suggests that 29% of men with BPH will eventually require surgical treatment for symptomatic BPH. This translates into more than 400,000 surgical resections of the prostate each year in the United States, with an annual cost of $4,000,000,000. This figure will grow even larger if we consider the fact that the current number of 22 million men >50 years of age in the United States will nearly double by the year 2010. In a search for more effective and less costly treatment modalities, efforts have been underway to find treatment alternatives for BPH. Recent progress in demonstrating efficacy for pharmacologic agents, such as alpha- androgenic blockers and 5-alpha-reductase inhibitors in reducing the symptoms of BPH, has raised new hope for the role of medical therapy in treatment of BPH. Two major deficiencies, however, prevent researchers from defining the exact role of these medications in the overall management of patients with BPH. First, there is a striking paucity of data on the epidemiology and pathogenesis of the disease. Second, critical questions about the clinical applicability of these agents remain unanswered. A randomized clinical trial is needed to address these questions and to provide a direction for understanding of the natural history of the disease. We propose a design for a pilot study for the evaluation of medical treatment for BPH in preparation for a full-scale clinical trial. Our proposal randomizes eligible patients with symptomatic BPH into one of the four simultaneous phase II clinical trials. The results of these phase II clinical trials would establish feasibility, toxicity and response rates for alpha-1-androgenic blockers, 5-alpha-reductase inhibitors, a combination of both alpha-1-androgenic blockers and 5-alpha-reductase inhibitors, and placebo. Importantly, response rates would be correlated to histologic features of patients' prostate glands. Satisfaction of the objectives of this pilot study would establish the prerequisites for a full-scale clinical trial. This trial could be designed as a phase III study of """"""""directed therapy"""""""" (i.e., treatment based on histologic features) versus """"""""non-directed therapy (i.e., treatment based on the best-result arm of the pilot study). The findings of the full-scale trial will provide us with required data to define the potential chemopreventive role of pharmacologic agents to halt or reverse the process of pathologic and clinical development of BPH.
