- Email: [email protected]
Discussion following DR. Don W. W. Newling’s presentation
in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N Engl J Med 337: 295–300, 1997. 6. Van den Ouden D, Tribukait B, Blom JHM, et al, and the EORTC Genitourinary Group: Deoxyribonucleic acid ploidy of core biopsies and metastatic lymph nodes of prostate cancer patients: impact on time to progression. J Urol 150: 400 – 406, 1993. 7. Medical Research Council Prostate Cancer Working Party Investigators Group: Immediate versus deferred treatment for advanced prostatic cancer: Initial results of the MRC trial. Br J Urol 79: 235–246, 1997. 8. Kirk D: MRC study: when to continue treatment in advanced prostate cancer. Prostate Cancer 1: 11–15, 1997.
9. Messing EM, Manola J, Sarosdy M, et al: Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med 34: 1781–1788, 1999. 10. Walsh PC: Urological survey. J Urol 164: 246 –247, 2000. 11. Cheng L, Bergstralh EJ, Cheville JC, et al: Cancer volume of lymph nodes metastasis predicts progression in prostate cancer. Am J Surg Pathol 22: 149 –155, 1998. 12. Serignoli AR, Walsh PC, Steinberg G, et al: Prognostic factors in men with stage D1 prostate cancer: identification of patients less likely to have prolonged survival after radical prostatectomy. J Urol 152: 1077–1081, 1994.
DISCUSSION FOLLOWING DR. DON W. W. NEWLING’S PRESENTATION William R. Fair, MD (New York, New York): Is early hormonal treatment something of the standard in Europe now? Don W.W. Newling, MBB, Chir (Amsterdam, the Netherlands): Patients in Europe are now demanding that something be done. Once we decide that we can’t cure them with radical prostatectomy or radiation therapy, they want some sort of treatment. We have therapies that are less toxic than castration now, and so I think we feel obliged to offer these therapies. It used to be quite easy before this information came out. I always felt from the Medical Research Council (MRC) study (no matter how badly people think it was carried out) that there was clear evidence of benefit with early hormonal therapy. But as that now seems to have gone away, it becomes harder to sell hormonal therapy as initial therapy. I can see that, in Europe, we are going to go to some form of intermittent therapy as soon as it is possible. Peter R. Carroll, MD (San Francisco, California): How do we draw the boundaries of this M0 patient population? I am concerned that this information will be used to move the paradigm to a very low-risk spectrum of disease, such as the patient with increasing prostate-specific antigen and the intermediate- and low-risk patients after radiation. We will need to identify phenotypes that identify patients who may need this therapy very early on. John Trachtenberg, MD (Toronto, Ontario, Canada): If you treat early, this is long duration. It may be that the benefits will be small in suppressing tumor growth, while it may be equally or more harmful in terms of side effects. No matter
UROLOGY 58 (2A), August 2001
how nontoxic a drug is, it does something. So we need to assess both how active the tumor is and how our benign treatments affect people. Only with that balance will we be able to select the appropriate treatment. Harry W. Daniell, MD (Redding, California): Do any patients in studies like yours get hormone levels assessed after primary therapy, before beginning androgen deprivation therapy (ADT)? A recent study showed that testosterone levels increased 20% or 30% after radical prostatectomy (J Urol 160: 449-453, 1998). We have done some studies that have shown striking differences between the hormone levels in men who have had primary radiation therapy and those who have had primary prostatectomy. The hormone levels after primary radiation therapy tend to decrease in our study. So it seems that this hormone profile, after primary therapy, would be important information to acquire before instituting ADT. Dr. Newling: In the early European Organization for Research on Treatment of Cancer (EORTC) studies, we measured testosterone levels before, during, and after primary therapy. A major problem is the diurnal variance of testosterone levels and the change in testosterone with age, which is not an all-or-nothing phenomenon. We found it so variable that we weren’t getting any solid messages from it. But endocrinologists now know so much more about androgen levels and the so-called andropause that it is worthwhile going back. There is a group in Ghent, Belgium, who are doing this now, and I hope that in a couple of years they will have some more information for us.
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9. Messing EM, Manola J, Sarosdy M, et al: Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med 34: 1781–1788, 1999. 10. Walsh PC: Urological survey. J Urol 164: 246 –247, 2000. 11. Cheng L, Bergstralh EJ, Cheville JC, et al: Cancer volume of lymph nodes metastasis predicts progression in prostate cancer. Am J Surg Pathol 22: 149 –155, 1998. 12. Serignoli AR, Walsh PC, Steinberg G, et al: Prognostic factors in men with stage D1 prostate cancer: identification of patients less likely to have prolonged survival after radical prostatectomy. J Urol 152: 1077–1081, 1994.
DISCUSSION FOLLOWING DR. DON W. W. NEWLING’S PRESENTATION William R. Fair, MD (New York, New York): Is early hormonal treatment something of the standard in Europe now? Don W.W. Newling, MBB, Chir (Amsterdam, the Netherlands): Patients in Europe are now demanding that something be done. Once we decide that we can’t cure them with radical prostatectomy or radiation therapy, they want some sort of treatment. We have therapies that are less toxic than castration now, and so I think we feel obliged to offer these therapies. It used to be quite easy before this information came out. I always felt from the Medical Research Council (MRC) study (no matter how badly people think it was carried out) that there was clear evidence of benefit with early hormonal therapy. But as that now seems to have gone away, it becomes harder to sell hormonal therapy as initial therapy. I can see that, in Europe, we are going to go to some form of intermittent therapy as soon as it is possible. Peter R. Carroll, MD (San Francisco, California): How do we draw the boundaries of this M0 patient population? I am concerned that this information will be used to move the paradigm to a very low-risk spectrum of disease, such as the patient with increasing prostate-specific antigen and the intermediate- and low-risk patients after radiation. We will need to identify phenotypes that identify patients who may need this therapy very early on. John Trachtenberg, MD (Toronto, Ontario, Canada): If you treat early, this is long duration. It may be that the benefits will be small in suppressing tumor growth, while it may be equally or more harmful in terms of side effects. No matter
UROLOGY 58 (2A), August 2001
how nontoxic a drug is, it does something. So we need to assess both how active the tumor is and how our benign treatments affect people. Only with that balance will we be able to select the appropriate treatment. Harry W. Daniell, MD (Redding, California): Do any patients in studies like yours get hormone levels assessed after primary therapy, before beginning androgen deprivation therapy (ADT)? A recent study showed that testosterone levels increased 20% or 30% after radical prostatectomy (J Urol 160: 449-453, 1998). We have done some studies that have shown striking differences between the hormone levels in men who have had primary radiation therapy and those who have had primary prostatectomy. The hormone levels after primary radiation therapy tend to decrease in our study. So it seems that this hormone profile, after primary therapy, would be important information to acquire before instituting ADT. Dr. Newling: In the early European Organization for Research on Treatment of Cancer (EORTC) studies, we measured testosterone levels before, during, and after primary therapy. A major problem is the diurnal variance of testosterone levels and the change in testosterone with age, which is not an all-or-nothing phenomenon. We found it so variable that we weren’t getting any solid messages from it. But endocrinologists now know so much more about androgen levels and the so-called andropause that it is worthwhile going back. There is a group in Ghent, Belgium, who are doing this now, and I hope that in a couple of years they will have some more information for us.
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