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RE: OSTEOPOROSIS AFTER ORCHIECTOMY FOR PROSTATE CANCER
1392
LETTERS TO THE EDITOR
nor and posterior prostate margins did not impart a worse prognosis on multivariate analysis. Patients with multiple margins had a higher rate of failure a t 5 years (68% progression-free survival) because of a greater incidence of positive base margins in specimens with multiple versus isolated margins. We recently analyzed 2,518 cases of specimen confined, stage pT2 to pT3NOMO cancer. Multivariate analysis considering the primary variables of Gleason score, preoperative prostate specific antigen, margin status, extraprostatic extension, seminal vesicle involvement and deoxyribonucleic acid ploidy indicates that a positive margin is a stronger predictor of biochemical failure than extraprostatic extension (relative risk 1.89, 95% confidence interval 1.51 to 2.36 versus 1.26, 1.01 to 1.55).4 Patients with extraprostatic extension and negative surgical margins may have a 5-year biochemical and progression-free status similar to that of patients with organ confined disease.5.6 Standard reporting of site specific margin status in radical prostatectomy specimens will be important when considering adjuvant therapy and alteration of surgical technique. Respectfully, Michael L. Blute and Horst Zincke Department of Urology Mayo Clinic Mayo Medical School 200 First St. S. W. Rochester, Minnesota 55905 1. Blute, M. L., Bostwick, D. G., Bergstralh, E. J., Slezak, J. M., Martin, S. K., Amling, C. L. and Zincke, H.: Anatomic sitespecific positive margins in organ-confined prostate cancer and its impact on outcome after radical prostatectomy. Urology, 50: 733, 1997. 2. Fesseha, T., Sakr, W., Grignon, D., Banejee, M., Wood, D. P., Jr. and Pontes, J. E.: Prognostic implications of a positive apical margin in radical prostatectomy specimens. J. Urol., 1 5 8 2176, 1997. 3. Rabbani, F., Bastar, A. and Fair, W. R.: Site specific predictors of positive margins a t radical prostatectomy: an argument for risk based modification of technique. J. Urol., 1 6 0 1727,1998. 4. Blute, M. L., Bergstralh, E. J., Iocca, A. and Zincke, H.: Prediction of biochemical failures after radical prostatectomy for specimen-confined prostate cancer. J. Urol., part 2, 161: 155, abstract 595, 1999.5. Lowe, B. and Lieberman, S. F.: Disease recurrence and progression in untreated pathologic stage T3 prostate cancer: selecting the patient for adjuvant therapy. J. Urol., 1 5 8 1452,1997. 6. Kausik, S. J., Blute, M. L.,Bergstralh, E. J., Slezak, J. and Zincke, H.: Evaluation of ositive margins in limited extracapsular prostate cancer a n f i t s impact on outcome after radical prostatectomy. J. Urol., part 2, 1 5 9 296, abstract 1143, 1998.
RE: OSTEOPOROSIS AFTER ORCHIECTOMY FOR PROSTATE CANCER H. W. Daniell
J. Urol., 157: 439-444, 1997
To the Editor. Wei et al make an elegant and convincing argument that more research is needed on osteoporosis in patients with prostate cancer who receive androgen deprivation.’ The success of estrogen therapy for preventing osteoporosis in women may be relevant to these men with prostate cancer. An abundance of data exists from the Veterans Administration Cooperative Urological Research Group studies regarding the safety and efficacy of primary estrogen therapy in men with prostate cancer. As pointed out by Byar and Corle.2 and supported in the exhaustive review of Cox and Crawford3 no form of endocrine therapy for prostate cancer has proved superior to 1 mg. diethylstilbestrol daily. The most serious side effect of diethylstilbestrol, thromboembolism, was not statistically different for 3 mg. diethylstilbestrol daily than for leuprolide treatment (p = 0.065h4 The efficacy of a 1 mg. dose has been questioned because it does not result in castrate testosterone levels in all men. Nevertheless, the therapeutic effect is maintained at this dose.3.5 Daniell pointed out that osteoporosis develops after orchiectomy for prostate cancer. Diethylstilbestrol treatment is equivalent to orchiectomy for cancer control but it may present significant advantages in terms of osteoporosis prevention. While bone densitometry was not part of the Veterans Administration Cooperative Urological Research Group studies, there is reason to believe that diethylstilbestrol. a synthetic estrogen, would maintain bone density while
providing hormonal control of cancer. Recent studies have unequivocally shown that estrogen maintains bone mass in men. Bilezikian et al demonstrated the reversal of osteoporosis with conjugated estrogens in a man with aromatase deficiency: and Eriksson et al reported stabilization of bone loss in 16 men treated with estrogen after hormonal deprivation therapy for prostate ~ a n c e r . ~ As Wei et a1 point out, osteoporosis induced fracture in men with advanced prostate cancer may be expected in almost 2,000 cases yearly in the United States. Diethylstilbestrol at a dose of 1 mg. daily has proved to be safe and effective as first or second line therapy in these patients.3.8 To our knowledge whether diethylstilbestrol as well as conjugated estrogens prevents osteoporosis remains unanswered. Data to this effect would pave the way to a resurgence of estrogen based therapy in men with prostate cancer. Respectfully, Christian P. Pavlovich and W. Reid Pitts, Jr. Department of Urology James Buchanan Brady Foundation New York Presbyterian Hospital-Cornell Medical Center 525 E. 68th St. New York, New York 10021 1. Wei, J., Gravlin, K. and Cooney, K. A,: Osteoporosis after orchiectomy for prostate cancer. Letter to the Editor. J. Urol., 1 6 0 1809,1998. 2. Byar, D. P. and Corle, D. K: Hormone therapy for prostate cancer: results of the Veterans Administration Cooperative Urological Research Group studies. Natl. Cancer Inst. Mongr., 7: 165, 1988. 3. Cox, R. L. and Crawford, E. D.: Estrogens in the treatment of prostate cancer. J. Urol., 1 5 4 1991, 1995. 4. Leuprolide versus diethylstilbestrol for metastatic prostate cancer. Leuprolide Study Group. New Engl. J. Med., 311: 1281, 1984. 5. Scott, W. W., Menon, M. and Walsh, P. C.: Hormonal therapy of prostate cancer. Cancer, suppl., 4 5 1929, 1980. 6. Bilezikian, J. P., Morishima, A,, Bell, J. and Grumbach, M. M.: Increased bone mass as a result of estrogen therapy in a man with aromatase deficiency. New Engl. J. Med., 339 599, 1998. 7. Eriksson, S., Eriksson, A, Stege, R. and Carlstrom, K: Bone mineral density in patients with prostatic cancer treated with orchidectomy and with estrogens. Calcif. Tissue Int., 57: 97, 1995. 8. Smith, E. P., Boyd, J.,Frank, G. R., Takahashi, H., Cohen, R. M., Specker, B., Williams, T. C., Lubahn, D. B. and Korach, K. S.: Estrogen resistance caused by a mutation in the estrogenreceptor gene in a man. New Engl. J. Med., 331: 1056, 1994. Reply by Author. We have also been impressed by the evidence presented by Wei et a1 (reference 1 in letter), and Pavlovich and Pitts, suggesting the reexamination of estrogen for treating prostate cancer. We have followed 2 men during treatment for prostate cancer with diethylstilbestrol and found no change in bone mineral density despite multiple risk factors for osteoporosis. We have recommended small doses of aspirin in these cases in an effort to decrease any tendency toward thromboembolic disease related to prostate cancer or hormonal therapy. Ample evidence indicates that aspirin should be included in any trial of estrogen for treating these tumors.
RE: CLAUDIUS GALEN: FROM A 20TH CENTURY GENITOURINARY PERSPECTIVE D. A. Bloom, M . T. Milen and J. C. Heininger
J. Urol., 161: 12-19, 1999 To the Editor. I read with great interest the article on Galen. As a former classics major, I must point out an error in formatting the name of Galen. The correct Latin version is Claudius Galenus and the Greek is Klaudios Galenos. Clarissimus is not a Greek translation of Claudius but a Latin honorific not much different from sir. Respectfully, Naomi E. Torrez Department of Medical Editing Kaiser Foundation Research Institute 1800 Harrison St., 16th Floor Oakland, California 94612-3429 To the Editor. I read this article with great interest. Despite the significant contributions of Claudius Galen (130 to 200 or 210 A.D.)
LETTERS TO THE EDITOR
nor and posterior prostate margins did not impart a worse prognosis on multivariate analysis. Patients with multiple margins had a higher rate of failure a t 5 years (68% progression-free survival) because of a greater incidence of positive base margins in specimens with multiple versus isolated margins. We recently analyzed 2,518 cases of specimen confined, stage pT2 to pT3NOMO cancer. Multivariate analysis considering the primary variables of Gleason score, preoperative prostate specific antigen, margin status, extraprostatic extension, seminal vesicle involvement and deoxyribonucleic acid ploidy indicates that a positive margin is a stronger predictor of biochemical failure than extraprostatic extension (relative risk 1.89, 95% confidence interval 1.51 to 2.36 versus 1.26, 1.01 to 1.55).4 Patients with extraprostatic extension and negative surgical margins may have a 5-year biochemical and progression-free status similar to that of patients with organ confined disease.5.6 Standard reporting of site specific margin status in radical prostatectomy specimens will be important when considering adjuvant therapy and alteration of surgical technique. Respectfully, Michael L. Blute and Horst Zincke Department of Urology Mayo Clinic Mayo Medical School 200 First St. S. W. Rochester, Minnesota 55905 1. Blute, M. L., Bostwick, D. G., Bergstralh, E. J., Slezak, J. M., Martin, S. K., Amling, C. L. and Zincke, H.: Anatomic sitespecific positive margins in organ-confined prostate cancer and its impact on outcome after radical prostatectomy. Urology, 50: 733, 1997. 2. Fesseha, T., Sakr, W., Grignon, D., Banejee, M., Wood, D. P., Jr. and Pontes, J. E.: Prognostic implications of a positive apical margin in radical prostatectomy specimens. J. Urol., 1 5 8 2176, 1997. 3. Rabbani, F., Bastar, A. and Fair, W. R.: Site specific predictors of positive margins a t radical prostatectomy: an argument for risk based modification of technique. J. Urol., 1 6 0 1727,1998. 4. Blute, M. L., Bergstralh, E. J., Iocca, A. and Zincke, H.: Prediction of biochemical failures after radical prostatectomy for specimen-confined prostate cancer. J. Urol., part 2, 161: 155, abstract 595, 1999.5. Lowe, B. and Lieberman, S. F.: Disease recurrence and progression in untreated pathologic stage T3 prostate cancer: selecting the patient for adjuvant therapy. J. Urol., 1 5 8 1452,1997. 6. Kausik, S. J., Blute, M. L.,Bergstralh, E. J., Slezak, J. and Zincke, H.: Evaluation of ositive margins in limited extracapsular prostate cancer a n f i t s impact on outcome after radical prostatectomy. J. Urol., part 2, 1 5 9 296, abstract 1143, 1998.
RE: OSTEOPOROSIS AFTER ORCHIECTOMY FOR PROSTATE CANCER H. W. Daniell
J. Urol., 157: 439-444, 1997
To the Editor. Wei et al make an elegant and convincing argument that more research is needed on osteoporosis in patients with prostate cancer who receive androgen deprivation.’ The success of estrogen therapy for preventing osteoporosis in women may be relevant to these men with prostate cancer. An abundance of data exists from the Veterans Administration Cooperative Urological Research Group studies regarding the safety and efficacy of primary estrogen therapy in men with prostate cancer. As pointed out by Byar and Corle.2 and supported in the exhaustive review of Cox and Crawford3 no form of endocrine therapy for prostate cancer has proved superior to 1 mg. diethylstilbestrol daily. The most serious side effect of diethylstilbestrol, thromboembolism, was not statistically different for 3 mg. diethylstilbestrol daily than for leuprolide treatment (p = 0.065h4 The efficacy of a 1 mg. dose has been questioned because it does not result in castrate testosterone levels in all men. Nevertheless, the therapeutic effect is maintained at this dose.3.5 Daniell pointed out that osteoporosis develops after orchiectomy for prostate cancer. Diethylstilbestrol treatment is equivalent to orchiectomy for cancer control but it may present significant advantages in terms of osteoporosis prevention. While bone densitometry was not part of the Veterans Administration Cooperative Urological Research Group studies, there is reason to believe that diethylstilbestrol. a synthetic estrogen, would maintain bone density while
providing hormonal control of cancer. Recent studies have unequivocally shown that estrogen maintains bone mass in men. Bilezikian et al demonstrated the reversal of osteoporosis with conjugated estrogens in a man with aromatase deficiency: and Eriksson et al reported stabilization of bone loss in 16 men treated with estrogen after hormonal deprivation therapy for prostate ~ a n c e r . ~ As Wei et a1 point out, osteoporosis induced fracture in men with advanced prostate cancer may be expected in almost 2,000 cases yearly in the United States. Diethylstilbestrol at a dose of 1 mg. daily has proved to be safe and effective as first or second line therapy in these patients.3.8 To our knowledge whether diethylstilbestrol as well as conjugated estrogens prevents osteoporosis remains unanswered. Data to this effect would pave the way to a resurgence of estrogen based therapy in men with prostate cancer. Respectfully, Christian P. Pavlovich and W. Reid Pitts, Jr. Department of Urology James Buchanan Brady Foundation New York Presbyterian Hospital-Cornell Medical Center 525 E. 68th St. New York, New York 10021 1. Wei, J., Gravlin, K. and Cooney, K. A,: Osteoporosis after orchiectomy for prostate cancer. Letter to the Editor. J. Urol., 1 6 0 1809,1998. 2. Byar, D. P. and Corle, D. K: Hormone therapy for prostate cancer: results of the Veterans Administration Cooperative Urological Research Group studies. Natl. Cancer Inst. Mongr., 7: 165, 1988. 3. Cox, R. L. and Crawford, E. D.: Estrogens in the treatment of prostate cancer. J. Urol., 1 5 4 1991, 1995. 4. Leuprolide versus diethylstilbestrol for metastatic prostate cancer. Leuprolide Study Group. New Engl. J. Med., 311: 1281, 1984. 5. Scott, W. W., Menon, M. and Walsh, P. C.: Hormonal therapy of prostate cancer. Cancer, suppl., 4 5 1929, 1980. 6. Bilezikian, J. P., Morishima, A,, Bell, J. and Grumbach, M. M.: Increased bone mass as a result of estrogen therapy in a man with aromatase deficiency. New Engl. J. Med., 339 599, 1998. 7. Eriksson, S., Eriksson, A, Stege, R. and Carlstrom, K: Bone mineral density in patients with prostatic cancer treated with orchidectomy and with estrogens. Calcif. Tissue Int., 57: 97, 1995. 8. Smith, E. P., Boyd, J.,Frank, G. R., Takahashi, H., Cohen, R. M., Specker, B., Williams, T. C., Lubahn, D. B. and Korach, K. S.: Estrogen resistance caused by a mutation in the estrogenreceptor gene in a man. New Engl. J. Med., 331: 1056, 1994. Reply by Author. We have also been impressed by the evidence presented by Wei et a1 (reference 1 in letter), and Pavlovich and Pitts, suggesting the reexamination of estrogen for treating prostate cancer. We have followed 2 men during treatment for prostate cancer with diethylstilbestrol and found no change in bone mineral density despite multiple risk factors for osteoporosis. We have recommended small doses of aspirin in these cases in an effort to decrease any tendency toward thromboembolic disease related to prostate cancer or hormonal therapy. Ample evidence indicates that aspirin should be included in any trial of estrogen for treating these tumors.
RE: CLAUDIUS GALEN: FROM A 20TH CENTURY GENITOURINARY PERSPECTIVE D. A. Bloom, M . T. Milen and J. C. Heininger
J. Urol., 161: 12-19, 1999 To the Editor. I read with great interest the article on Galen. As a former classics major, I must point out an error in formatting the name of Galen. The correct Latin version is Claudius Galenus and the Greek is Klaudios Galenos. Clarissimus is not a Greek translation of Claudius but a Latin honorific not much different from sir. Respectfully, Naomi E. Torrez Department of Medical Editing Kaiser Foundation Research Institute 1800 Harrison St., 16th Floor Oakland, California 94612-3429 To the Editor. I read this article with great interest. Despite the significant contributions of Claudius Galen (130 to 200 or 210 A.D.)