Antagonists and Analogues in Prostate Cancer

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Dr. Hans van der Slikke: "Good morning, we're here in Geneva at the 6th Analogue Conference and next to me is Professor Bartsch from Innsbruck. He's the Head of the Department of Urology and he's talking about antagonists and analogues in prostate cancer. Professor Bartsch, could you explain to us what exactly is the advantage of the antagonist these days in prostate cancer?"

Dr. G. Bartsch: "If you give an analogue of GnRH then you give a substance which is very similar to GnRH and, therefore, what you're doing first of all is you're going to stimulate GnRH and, therefore, you get a surge of LH and you get a surge of testosterone. If you give a GnRH antagonist, which is competitive to GnRH receptor signs, you get no surge so you get a total depression of LH and testosterone. What's even more interesting is if you look at the FSH levels. The FSH levels cannot be suppressed by GnRH analogues but they can be suppressed by GnRH antagonists. At the time we don't know the input of FSH but we have realized in the last couple of years that it's not only androgens which influence prostate growth and benign prostatic hyperplasia as well as in prostate cancer but it is a multi-hormonal disease. At this time there are very good studies going on in the United States showing FSH and FSH receptors in prostate carcinoma specimens, in radical prostatectomy specimens, and in the high-grade PIN lesions as well."

Dr. Hans van der Slikke: "That means it's not only dependent of the androgen receptor?"

Dr. G. Bartsch: "This is the task of the symposium to show the biology of this disease. If you don't have androgens you still have the androgen receptor and the androgen receptor is just synthesized by non sterile activation life by growth factors and you have a cross-talk with growth factors like IGF or EGF or KGF and the androgen receptor doesn't use androgens to pre-synthesize, it just uses growth factors."

Dr. Hans van der Slikke: "Are there many antagonists on the market already?"

Dr. G. Bartsch: "No, actually not. It's very limited, we have a Phase II and a Phase III study with a very good GnRH antagonist, and we're looking forward to new studies. The most interesting point, however, is to look and get more insight to the mechanism of FSH to tumor growths of prostate cancer."

Dr. Hans van der Slikke: "Do you think more insight could also lead to more, let's say, prevention of prostate cancer?"

Dr. G. Bartsch: "The problem of prostate cancer is that it's the most common cancer in males; it's the second leading cause of death in men after lung cancer. If you look, since 1930, we have not improved mortality and as a clinician you have three options to reduce mortality. One is prevention, one is to screen, and one is to find a better treatment for the metastatic lesion. This substance should be on the third way to find a better treatment for the metastatic lesion."

Dr. Hans van der Slikke: "I see, and so the best way is to do screening on prostate cancer. If you can do a good screening, perhaps, you can do an area intervention?"

Dr. G. Bartsch: "You know screening is highly controversial but when you ask me I'm very pro for screening. In the country where I'm living, we have done a big screening study and for three years we have decreased mortality of 38%, 42%, and 39% of the patients."

Dr. Hans van der Slikke: "What kind of screening do you do?"

Dr. G. Bartsch: "PSA screening, and it's very simple. Screening must be very simple because otherwise the population does not accept it. The population isn't going to urologists; they are just going to a general practitioner or to a nurse or just taking blood and PSA. You do your total PSA and you do your free PSA and then you decide if you will do a biopsy or not. Then when you have small tumors, you can do a radical prostatectomy and you can do this without harming potency. Patients are potent after the operation and patients are continent, this means with the type of operation we have today the patients are continent to 97% and they are potent to 84%."

Dr. Hans van der Slikke: "That's a lot, so despite the progress, mortality is not so far. There is a good hope that in the near future the results will be a lot better."

Dr. G. Bartsch: "We have to because we're all becoming older and as we're becoming older prostate cancer will increase. Prostate cancer today - and you can see this in all types of literature, which is written in northern Europe and the United States - is the number one killer, it's a so-called silent killer. We as physicians have to face the community, we have to help the community, and we have to help find out how to cure cancer."

Dr. Hans van der Slikke: "Professor Bartsch, thank you very much."

Dr. G. Bartsch: "Thank you."