Now if we know something about the epidemiology of prostate cancer, maybe we can get some hypotheses regarding the prevention of this disease. Suffice it to say that there have been no prospective randomized studies with intervention that have confirmed that any of these hypotheses work. Although there are some suggestions that dietary fat is important, selenium ingestion, vitamin E, soy and lycopene are important. Thus far one cannot make a strong recommendation to do these things to prevent the disease.

Now let’s move on to some more clinically relevant subjects, particularly screening for prostate cancer. So let me summarize 10-15 years of work that’s been done in screening in one slide. I think this summarizes much of what we know right now. In the old days the screening test that we had for prostate cancer was the digital rectal exam. A lot of inter-observer variability. When one detects an abnormality by digital rectal exam, more often than not is the tumor outside of the prostate. When you combine the digital rectal exam with the prostate specific antigen you can detect three times as many cancers as one did by the digital rectal exam alone. From the Physicians Health Study we learned that when one uses PSA one can detect clinically undetectable cancer on average 5-6 years earlier than one would detect by digital rectal exam or the development of symptomatology. In the big screening studies the majority of cases are diagnosed within the first couple of years. With subsequent screening that the incidence rate falls off significantly. One of the big concerns with PSA screening was that what was being detected were so-called autopsy or latent cancers, these low grade, microscopic foci of prostate cancer that one dies with rather than of. Now it turns out that by pathological criteria, greater than 90% of the PSA-detected cancers are not autopsy cancers. They are not low grade, low volume cancers but are cancers of significant volume and higher grade. Now whether these cancers are truly clinically significant in the sense that these cancers, if left untreated would ultimately cause mortality, remains uncertain. In these screening studies about 5% of men over the age of 50 who come in for a digital rectal exam and PSA will be found to have an abnormality in one or both of those tests and ultimately will be found to have prostate cancer. Although PSA is not a perfect screening test, there is a relationship with the likelihood of having prostate cancer. The level of the PSA does predict the likelihood. Where 25% of patients or people who have a PSA between 4-10 have prostate cancer, you can see the problem here is that 75% of these people do not. The vast majority of people with PSA’s over 10 will turn out to have prostate cancer.

Now the big question with screening for prostate cancer is whether the strategy of PSA-based screening will reduce the mortality from the disease. There is one screening study that was presented at ASCO two years ago that was so methodologically flawed that we don’t use it as evidence for screening, but it did show some benefit for screening. Some people have looked at the slight reduction in mortality of this disease in the United States over the past few years as evidence that the screening strategy in the United States has reduced mortality, but it may be a little too early to declare victory at this point.

What we have noticed clinically in the United States – this is once again from the SERE cancer registry in the United States – these are the rates of stages C and D prostate cancer at presentation in Caucasian and African-Americans. What we do see over the past five to ten years not surprisingly, stage migration where there are fewer and fewer patients who come in the door with stages C and D. The disease has shifted to earlier disease.