This year there will be almost 180,000 cases of prostate cancer diagnosed, and 37,000 deaths from the disease. There has been a very interesting pattern of incidence of prostate cancer in the United States over the past 30 years, which is illustrated by this slide, in the African-American population which is the top curve and in the Caucasian population in the United States. As you can see, over the past 20-30 years there was a steady but slow rise in the incidence of prostate cancer in these two populations, beginning in the later 1980’s, 1990’s, a rapid increase in incidence rates. This we attribute to several factors; increasing awareness, greater ease of doing biopsies, the development of the biopsy gun, but most importantly the introduction and widespread use of the prostate-specific antigen, which had detected many clinically undetected cancers in the population. What’s most interesting about these curves is the decline in incidence over the past few years, which we think is attributable to the fact that what we have done is cull out of the population many of the prevalence cases of prostate cancer that were not diagnosed because they were clinically silent, and now we are decreasing to another true incidence rate of prostate cancer as would be detected largely by elevations of PSA. So the majority of the patients that we are now seeing in the clinic are patients who are detected by PSA alone.
Now this is how we think of prostate cancer. Prostate cancer is the disease that arises in the epithelium of the prostate. The first recognizable pathological entity is known as prostatic intraepithelial neoplasia, which is the prostatic equivalent of carcinoma in situ in breast cancer; which in contrast to bladder cancer, is not a nasty entity but a disease that may coexist with invasive prostate cancer or may ultimately become prostate cancer. If you see this in a patient with an elevated PSA on biopsy, what is required is a repeat biopsy in the next few months. Because at high frequency, these patients actually have concomitant prostate cancer. The evolution of PIN to invasive prostate cancer probably takes place over years but the natural history of this disease is not really understood. Ultimately invasive prostate cancer will develop and invasive prostate cancer stretches all the way from so-called latent or autopsy prostate cancer – little microscopic foci of low-grade, low-volume prostate cancer – to bulky locally advanced prostate cancer.
Ultimately prostate cancer will metastasize and generally it consists of a heterogenous group of cells which are both androgen sensitive and androgen insensitive. So the strategy in patients with advanced disease is to remove androgen and remove the androgen sensitive population, reduce tumor bulk. Patients will almost always go into a remission but ultimately what emerges is a pure population of androgen insensitive cells and almost always this is the reason why a patient with prostate cancer will die, is the growth and spread of the hormone-refractory tumor cell population.