Understanding the epidemiology, natural history, and key pathways involved in prostate cancer.

Prostate cancer accounts for about 25% of all the newly diagnosed cancers in American men and was projected to cause >28,000 deaths in 2008. Black men are disproportionately affected; their incidence rate is about 1.6 times greater than the rate for white men. As the population ages, the number of new cases per year is expected to increase by >60% and reach 300,000 by 2015. This high incidence, coupled with the protracted onset of the disease, makes PCa a particularly appropriate candidate for prevention and early intervention strategies. Potential disease precursors, particularly high-grade prostatic intraepithelial neoplasia, might help identify men at high risk of developing PCa. Dihydrotestosterone, a product converted from testosterone by 5alpha-reductases, plays an important role in normal prostate growth and in the development of PCa. The 5alpha-reductase levels, particularly type 1, appear to increase during the disease course of prostatic intraepithelial neoplasia and PCa, with greater expression occurring as the disease progresses. Therefore, the inhibition of 5alpha-reductase could potentially reduce the risk of PCa development, slow or prevent disease progression, and/or treat existing disease. A substantial research effort has recently focused on understanding the pathways involved in the disease's emergence and progression, particularly the 5alpha-reductase pathway.