- Email: [email protected]
Discussion following Dr. Klotz’s presentation
domized trial of neoadjuvant androgen ablation before radical prostatectomy: 36-month post-treatment PSA results. Canadian Urologic Oncology Group. Urology 53: 757–763, 1999. 14. Gleave ME, Goldenberg SL, Jones EC, et al: Biochemical and pathological effects of 8 months of neoadjuvant androgen withdrawal therapy before radical prostatectomy in patients with clinically confined prostate cancer. J Urol 155: 213–219, 1996. 15. Gleave ME, Hsieh JT, Wu H-C, et al: Serum PSA levels in mice bearing human prostate LNCaP tumors are determined by tumor volume and endocrine and growth factors. Can Res 52: 1598 –1605, 1992.
16. Gleave ME, La Bianca SE, Goldenberg SL, et al: Longterm neoadjuvant hormone therapy prior to radical prostatectomy: evaluation of risk for biochemical recurrence at 5-year follow-up. Urology 56: 289 –294, 2000. 17. Meyer F, Moore L, Bairati I, et al: Neoadjuvant hormonal therapy before radical prostatectomy and risk of prostate specific antigen failure. J Urol 162: 2024 –2028, 1999. 18. Gleave ME, Goldenberg SL, Chin JL, et al: The Canadian Uro-Oncology Group. Randomized comparative study of 3 versus 8-month neoadjuvant hormonal therapy before radical prostatectomy: biochemical and pathological effects. J Urol 166: 500 –506, 2001.
DISCUSSION FOLLOWING DR. KLOTZ’S PRESENTATION Philip W. Kantoff, MD (Boston, Massachusetts): Are there subgroups where the rate of downstaging to P0 disease is significantly higher? Laurence Klotz, MD (Toronto, Ontario, Canada): My understanding is that the P0 rate, even with 8 months, is still relatively low, and I am not aware of any stratification variables that allow you to predict regression to stage P0. It is also a question of how reliable a P0 is after prolonged androgen deprivation therapy (ADT). The analogy to me is the pixel phenomenon. As you turn the pixels down on your monitor, what you see becomes more and more transparent and harder to visualize. To say that P0 after prolonged ADT is equivalent to P0 without neoadjuvant therapy is really a stretch. Most of those patients still have some residual cancer. It just may not be apparent. Anthony V. D’Amico MD, PhD (Boston, Massachusetts): Trials of 3 or 4 months of neoadjuvant hormonal therapy before surgery show no difference in prostate-specific antigen (PSA) outcome. Is this right? Now we have a 3-month arm and an 8-month arm. You say you are confident that it is going to show a difference in PSA. The implication is you are confident it is going to show a difference in PSA because of the testosterone recovery differing between the 2 arms, not because you think there’s a therapeutic effect. Dr. Klotz: I am confident, based on the difference in androgen recovery rates, that we will see a difference in PSA progression. Whether this is caused by hormonal effects or because of true differences in cancer cure, I think is a question.
UROLOGY 60 (Supplement 3A), September 2002
Matthew R. Smith, MD, PhD (Boston, Massachusetts): The assumption here is that slightly decreased testosterone levels would delay PSA progression. To my knowledge, there has never been a formal demonstration of the dose-response relation between testosterone and PSA expression in men. We know that if you treat men with castration, you decrease their testosterone levels. No one has ever shown, in a controlled trial, that if you just modestly decrease or delay the rate of testosterone return, that you have a PSA effect. The testosterone dose-response relation is different in different tissues, muscle, bone, and presumably in the prostate, and what it is in the prostate is unknown. Dr. Klotz: That is fair enough. I agree with you that we do not have the data. But probably it stands to reason. A population with diminished gonadal function will have a lower PSA than a population with normal gonadal function. Peter R. Carroll, MD (San Francisco, California): Why did you pick a PSA cutoff point of 0.3 ng/mL? If you use a cut point of 0.1 ng/mL, this difference might actually collapse. Dr. Klotz: The study was designed in 1994 and started in 1995, and that was the standard— 0.2 to 0.3 ng/mL. Now, 0.02 is the cutoff for the assay that has been used for the study, and these patients all have central PSA assays, collected by a single lab as well as at individual institutions. The endpoint was 0.3 ng/mL, but we will certainly have the data down to significantly lower levels. I do not think that will be an issue.
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16. Gleave ME, La Bianca SE, Goldenberg SL, et al: Longterm neoadjuvant hormone therapy prior to radical prostatectomy: evaluation of risk for biochemical recurrence at 5-year follow-up. Urology 56: 289 –294, 2000. 17. Meyer F, Moore L, Bairati I, et al: Neoadjuvant hormonal therapy before radical prostatectomy and risk of prostate specific antigen failure. J Urol 162: 2024 –2028, 1999. 18. Gleave ME, Goldenberg SL, Chin JL, et al: The Canadian Uro-Oncology Group. Randomized comparative study of 3 versus 8-month neoadjuvant hormonal therapy before radical prostatectomy: biochemical and pathological effects. J Urol 166: 500 –506, 2001.
DISCUSSION FOLLOWING DR. KLOTZ’S PRESENTATION Philip W. Kantoff, MD (Boston, Massachusetts): Are there subgroups where the rate of downstaging to P0 disease is significantly higher? Laurence Klotz, MD (Toronto, Ontario, Canada): My understanding is that the P0 rate, even with 8 months, is still relatively low, and I am not aware of any stratification variables that allow you to predict regression to stage P0. It is also a question of how reliable a P0 is after prolonged androgen deprivation therapy (ADT). The analogy to me is the pixel phenomenon. As you turn the pixels down on your monitor, what you see becomes more and more transparent and harder to visualize. To say that P0 after prolonged ADT is equivalent to P0 without neoadjuvant therapy is really a stretch. Most of those patients still have some residual cancer. It just may not be apparent. Anthony V. D’Amico MD, PhD (Boston, Massachusetts): Trials of 3 or 4 months of neoadjuvant hormonal therapy before surgery show no difference in prostate-specific antigen (PSA) outcome. Is this right? Now we have a 3-month arm and an 8-month arm. You say you are confident that it is going to show a difference in PSA. The implication is you are confident it is going to show a difference in PSA because of the testosterone recovery differing between the 2 arms, not because you think there’s a therapeutic effect. Dr. Klotz: I am confident, based on the difference in androgen recovery rates, that we will see a difference in PSA progression. Whether this is caused by hormonal effects or because of true differences in cancer cure, I think is a question.
UROLOGY 60 (Supplement 3A), September 2002
Matthew R. Smith, MD, PhD (Boston, Massachusetts): The assumption here is that slightly decreased testosterone levels would delay PSA progression. To my knowledge, there has never been a formal demonstration of the dose-response relation between testosterone and PSA expression in men. We know that if you treat men with castration, you decrease their testosterone levels. No one has ever shown, in a controlled trial, that if you just modestly decrease or delay the rate of testosterone return, that you have a PSA effect. The testosterone dose-response relation is different in different tissues, muscle, bone, and presumably in the prostate, and what it is in the prostate is unknown. Dr. Klotz: That is fair enough. I agree with you that we do not have the data. But probably it stands to reason. A population with diminished gonadal function will have a lower PSA than a population with normal gonadal function. Peter R. Carroll, MD (San Francisco, California): Why did you pick a PSA cutoff point of 0.3 ng/mL? If you use a cut point of 0.1 ng/mL, this difference might actually collapse. Dr. Klotz: The study was designed in 1994 and started in 1995, and that was the standard— 0.2 to 0.3 ng/mL. Now, 0.02 is the cutoff for the assay that has been used for the study, and these patients all have central PSA assays, collected by a single lab as well as at individual institutions. The endpoint was 0.3 ng/mL, but we will certainly have the data down to significantly lower levels. I do not think that will be an issue.
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