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DISCUSSION

Dr. Eric Klein. Are there requirements regarding how many biopsies are done for eligibility in the REDUCEtrial?

Dr. Bob Djavan. I believe that there must be 12 at baseline. These are biopsies that the men had undergonepreviously and were not part of the study.

CHEMOTHERAPEUTIC PREVENTION STUDIES OF PROSTATE CANCER S13

Doctor Klein: Do men who have an increased PSA and 1 negative biopsy actually have a higher risk of prostatecancer than someone who has never been biopsied?

Doctor Djavan: I published data from the European Prostate Cancer Detection study in which we looked atabout 2,000 men who underwent repeat biopsies systematically 8 weeks after the first biopsy. The cancerdetection rate on the first biopsy was just about 20% to 25% but the repeat biopsy rate within 8 weeks was 10%to 12%. If you performed a third biopsy 8 weeks later and then a fourth biopsy the rate went down to 3% to 4%.

Doctor Klein: If you take men who have an increased PSA and 1 negative biopsy is the cancer you might findon the second biopsy significant or not? Is this a rational trial design as opposed to just taking men who havenever been biopsied and who have an increased PSA? Are you going to be biopsying men who had an increasedPSA due to BPH? Are you double selecting for that subgroup?

Dr. Louis J. Denis. Our attitude is that you serve the population best with minimal requirements, which is whywe do not repeat biopsies until 1 year later. I think biopsies are still a big problem in the diagnosis of prostatecancer.

Dr. E. David Crawford. All things being equal, I agree that the yield on positive biopsies is less except in menwith increased PSAs.

Doctor Klein: So what you are showing here is the risk. The data show that when a man has a PSA less than10, he has a lower risk of having cancer if he has been biopsied once which was negative than if he had never beenbiopsied.

Dr. Ian M. Thompson. This does not include multiple repeat biopsies.Dr. Alan R. Kristal. The other critical point is that it is a more classical incidence study and the interpretation

becomes different. If you remove people with disease from your population, you are then looking at true incidenceand not period prevalence.

Dr. Neil Fleshner. I think the point is that arguably even the SELECT trial is an intervention trial because youare preventing the progression of small disease into disease detectable by a needle biopsy.

Doctor Djavan: The PCPT is looking at really healthy individuals, while our study is of a high risk populationwith higher PSA although biopsies are negative. The problem with PCPT and REDUCE is that the biopsybecomes your judge. All of these trials are looking at cancer incidence but the factor that decides whether canceris present is the biopsy. Since a biopsy is a sample, it is actually the weakest determinant. The cancer we findon the first repeat biopsy is the same cancer we found on the first biopsy. The third and fourth biopsy findingsbecome “insignificant.” The problem with first and repeat biopsies is the issue of sampling. We eventually willbiopsy more cores initially or biopsy them differently, which will allow us to find all of the cancers on the firstbiopsy.

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