- Email: [email protected]
RE: PROGNOSIS OF PATIENTS WITH LYMPH NODE POSITIVE PROSTATE CANCER FOLLOWING RADICAL PROSTATECTOMY: LONG-TERM RESULTS
0022-5347/05/1743-1151/0 THE JOURNAL OF UROLOGY® Copyright © 2005 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 174, 1151–1156, September 2005 Printed in U.S.A.
Letters to the Editor/Errata RE: BACILLUS CALMETTE-GUERIN VERSUS EPIRUBICIN FOR PRIMARY, SECONDARY OR CONCURRENT CARCINOMA IN SITU OF THE BLADDER: RESULTS OF A EUROPEAN ORGANIZATION FOR THE RESEARCH AND TREATMENT OF CANCER–GENITO-URINARY GROUP PHASE III TRIAL (30906)
2. Freedman, L. S. and White, S. J.: On the use of Pocock and Simon’s method for balancing treatment numbers over prognostic factors in the controlled clinical trial. Biometrics, 32: 691, 1976 DOI: 10.1097/01.ju.0000169425.93927.7a
T. M. de Reijke, K. H. Kurth, R. J. Sylvester, R. R. Hall, M. Brausi, K. van de Beek, K. E. J. Landsoght, P. Carpentier and Members of the European Organization for the Research and Treatment of Cancer-Genito-Urinary Group
RE: PROGNOSIS OF PATIENTS WITH LYMPH NODE POSITIVE PROSTATE CANCER FOLLOWING RADICAL PROSTATECTOMY: LONG-TERM RESULTS
J Urol, 173: 405– 409, 2005 To the Editor. We read this article with interest, and would like the authors to comment on several topics. The study uses complete response rate as the primary outcome for the sample size calculation. If ␣ ⫽ 0.1, 1 ⫺  ⫽ 0.8, P0 ⫽ 80%, effect size (P0 ⫺ P1) ⫽ 15%, using the popular formula for calculating sample size, N ⫽ 147 (per group). Also, using available computer software such as PS, Power and Sample Size Calculation, version 2.1.31 (Vanderbilt University Medical Center, Nashville, Tennessee), we obtained 109 samples per study arm, which is different from the 65 samples per study arm in the article. In addition, the patients were selected from 28 institutions in several European countries. Which method was used to generate random allocation sequence or to implement allocation concealment? Finally, the study was designed for analysis by intent to treat principle. In the results section the authors state, “Because 130 evaluable patients were required, 168 were entered to compensate for ineligible patients and those in whom the response to treatment could not be assessed due to absent followup biopsies.” This statement seems to contradict the intent to treat analysis principle. Respectfully, Darab Mehraban and Fatemeh Esfahani Urology Section Dr. Shariati Hospital Tehran University of Medical Sciences Tehran, Iran
Reply by Authors. Concerning the sample size calculation, the equation given by Mehraban and Esfahani is correct when testing for a difference in response rates. For a 2-sided test using ␣ ⫽ 0.10, Z1-␣/2 ⫽ 1.645. For a power of 80%, Z1- ⫽ 0.842 and N ⫽ 109. For a power of 90%, Z1- ⫽ 1.282 and N ⫽ 150. These are the figures quoted in the letter. However, this same equation cannot be used for testing noninferiority, since as stated in the article, the null hypothesis is no longer “no difference” in response rates. The correct formula is given by Blackwelder:1
S. Daneshmand, M. L. Quek, J. P. Stein, G. Lieskovsky, J. Cai, J. Pinski, E. C. Skinner and D. G. Skinner J Urol, 172: 2252–2255, 2004 To the Editor. This interesting article adds clarity to an important issue. The incidence of lymph node metastases is approximately 5% in current series of clinically localized prostate cancer.1, 2 This rate may reflect earlier detection of the disease due to widespread prostate specific antigen (PSA) testing and a limitation of standard lymph node dissection. In fact, in recent studies more extended lymphadenectomy has been proposed to obtain more accurate staging3 or even a possible chance of cure.4 Of course, extended dissection yields a higher number of lymph nodes, as studies comparing extended dissection to standard dissection have revealed.1– 4 However, some facts deserve attention. The number of positive lymph nodes does not reach a statistically significant difference regardless of the type of dissection that is carried out, as reported in randomized studies.5, 6 Ample variation exists in the number of lymph nodes that can be obtained at lymphadenectomy, and depends on several factors, namely anatomical boundaries, en bloc or separate removal, thickness and number of sections examined by the pathologist, lymph node biology and lack of a “routine” pattern of lymphatic spread.1, 7–9 The percentage of positive nodes demonstrates only a weak association with the total number, as illustrated in the figure. Conversely, the percentage of positive nodes depends on the extent of local disease (ie pathological tumor stage category),4 and average tumor volume (average tumor volume in this study was 2.3 cc overall and 10.9 cc for the node positive group).5 In a multivariate analysis the percentage of positive nodes (ie 15% or greater) together with a Gleason prostatectomy score of 8 to 10 and seminal vesicle invasion appeared to predict PSA progression in node positive cases.2 It appears clear that by extending the boundaries of lymph node dissection a higher proportion of cases of smaller volume disease can be detected. However, it should be emphasized that the benefit that can be observed in PSA progression-free survival is likely the consequence of reduced tumor burden rather than simply the effect of
共 Z 1-␣⫹Z1-)2[P0(1⫺P0)⫹P1(1⫺P1)]/(P0⫺P1⫺␦)2. In our case Z1-␣ ⫽ Z0.90 ⫽ 1.282, Z1- ⫽ Z0.80 ⫽ 0.842, P0 ⫽ P1 ⫽ 0.80 and ␦ ⫽ 0.15. This equation yields N ⫽ 65 patients in each group. Investigators had to contact the European Organization for the Research and Treatment of Cancer Data Center by telephone or the Internet to register and randomize patients. Patients were centrally randomized using the minimization technique, with stratification for institution, type of carcinoma in situ (primary, secondary, concurrent) and number of biopsies with carcinoma in situ (1, more than 1).2 Following the intent to treat principle all 168 randomized patients were included in the analyses. Since 33 patients could not be assessed for response to treatment, their inclusion in the analysis could dilute the size of any treatment difference that might exist. As the goal was to try to show that there was no difference in complete response rates, 38 additional patients were entered in an effort not to underestimate the size of any potential treatment difference. 1. Blackwelder, W. C.: “Proving the null hypothesis” in clinical trials. Control Clin Trials, 3: 345, 1982 1151
Numbers in graph indicate studies as they are listed in references
1152
LETTERS TO THE EDITOR
lymph node removal. Furthermore, extended dissection is associated with a higher incidence of surgical complications.3– 6 Respectfully, Massimo Maffezzini Struttura Complessa di Urologia Ospedale Galliera Mura delle Cappuccine 14 16128 Genova, Italy
Reply by Authors. We agree that there is great variation in the boundaries of pelvic lymph node dissection and the reported number of positive lymph nodes obtained at lymphadenectomy. The percentage of positive lymph nodes is dependent on the number of lymph nodes obtained, and, therefore, is a reflection of the extent of lymph node dissection. Bader et al reported that extending lymph node dissection to the internal iliac nodes not only yields more lymph nodes, but also yields positive nodes that would otherwise have been missed in a standard lymph node dissection.10 In their series 19% of patients had positive lymph nodes in the internal iliac lymph node chain only. The average number of lymph nodes obtained in their series was 21, similar to our node count of 19. Allaf et al from the Johns Hopkins group also found that extended lymph node dissection not only removed more lymph nodes, but also detected more lymph node positive disease (3.2% vs 1.1%, p ⬍0.0001) than the more anatomically limited technique.1 This finding held true for patients across all pathological subgroups. The complication rate in these series, including ours, is low and comparable to the more limited lymph node dissection technique. Conversely, Clark et al performed a randomized study that compared standard lymph node dissection to extended lymph node dissection on the contralateral side in the same patient.5 Extended lymph node dissection included the external iliac nodes to a point above the bifurcation of the common iliac artery, the obturator nodes and the presacral nodes. There was no difference observed in the incidence of positive lymph nodes in extended lymph node dissection. Perhaps a difference would have been observed if the internal iliac nodes had been included in the extended dissection. Numerous studies have shown that patients with a limited number of positive lymph nodes in fact have longer survival than those with more lymph node involvement, similar to radical cystectomy series.4, 10 –12 By reporting the absolute number of positive lymph nodes as well as the positive lymph node density (LND) we attempted to clarify the extent of disease in the lymph nodes. Having 1 positive node from a total of 4 (LND 25%) is a different clinical scenario than having 2 positive nodes from a total of 20 (LND 10%). We agree that reduced tumor burden (T stage) has a significant impact on progression-free survival. However, we believe that the removal of limited (1 or 2) positive lymph nodes serves as an independent prognostic factor and may offer long-term survival. REFERENCES
1. Allaf, M. E., Palapattu, G. S., Trock, B. J., Carter, H. B. and Walsh, P. C.: Anatomical extent of lymph node dissection: impact on men with clinically localized prostate cancer. J Urol, 172: 1840, 2004 2. Palapattu, G. S., Allaf, M. E., Trock, B. J., Epstein, J. I. and Walsh, P. C.: Prostate specific antigen progression in men with lymph node metastases following radical prostatectomy: results of long-term followup. J Urol, 172: 1860, 2004 3. Heidendreich, A., Varga, Z. and Knobloch, R.: Extended pelvic lymphadenectomy in patients undergoing radical prostatectomy: high incidence of lymph node metastasis. J Urol, 167: 1681, 2002 4. Bader, P., Burkhard, F. C., Markwalder, R. and Studer, U. E.: Disease progression and survival of patients with positive lymph nodes after radical prostatectomy. Is there a chance of cure? J Urol, 169: 849, 2003 5. Clark, T., Parekh, D. J., Cookson, M. S., Chang, S. S., Smith, E. R., Jr., Wells, N. et al: Randomized prospective evaluation of extended versus limited lymph node dissection in patients with clinically localized prostate cancer. J Urol, 169: 145, 2003 6. Stone, N. N., Stock, R. G. and Unger, P.: Laparoscopic pelvic lymph node dissection for prostate cancer: comparison of the extended and modified techniques. J Urol, 158: 1891, 1997 7. Bochner, B. H., Herr, H. W. and Reuter, V. E.: Impact of separate versus en bloc pelvic lymph node dissection on the number of
lymph nodes retrieved in cystectomy specimens. J Urol, 166: 2295, 2001 8. McLaughlin, A. P., Saltzstein, S. L., McCullough, D. L. and Gittes, R. F.: Prostatic carcinoma: incidence and location of unsuspected lymphatic metastases. J Urol, 115: 89, 1976 9. Wawroschek, F., Vogt, H., Weckermann, D., Wagner, T., Hamm, M. and Harzmann, R.: Radioisotope guided pelvic lymph node dissection for prostate cancer. J Urol, 166: 1715, 2001 10. Bader, P., Burkhard, F. C., Markwalder, R. and Studer, U. E.: Is a limited lymph node dissection an adequate staging procedure for prostate cancer? J Urol, 168: 514, 2002 11. Cheng, L., Zincke, H., Blute, M. L., Bergstralh, E. J., Scherer, B. and Bostwick, D. G.: Risk of prostate carcinoma death in patients with lymph node metastasis. Cancer, 91: 66, 2001 12. Frazier, H. A., 2nd, Robertson, J. E. and Paulson, D. F.: Does radical prostatectomy in the presence of positive pelvic lymph nodes enhance survival? World J Urol, 12: 308,1994 DOI: 10.1097/01.ju.0000169157.74608.3a
RE: CURRENT STATUS OF LOCAL SALVAGE THERAPIES FOLLOWING RADIATION FAILURE FOR PROSTATE CANCER N. J. Touma, J. I. Izawa and J. L. Chin J Urol, 173: 373–379, 2005 To the Editor. The authors provide an overview of treatment options after local failure following radiation therapy of localized prostate cancer. In this regard we would like to add our experience with thermal ablation techniques, which may also be used to treat local recurrence of localized prostate cancer. Magnetically mediated heating of iron oxide nanoparticles is a novel treatment approach that has been evaluated in animal models, including prostate cancer.1 Using this nanotechnology, temperatures of up to 70C can be achieved in the prostate during exposure to an alternating current magnetic field.2 At our institution thermotherapy using magnetic nanoparticles is currently being evaluated in patients with local failure following radiation therapy for prostate cancer. From our initial experience this approach is feasible and well tolerated.3 We have previously evaluated ferromagnetic seeds for thermotherapy of prostate cancer in combination with irradiation.4 These temperature self-regulating seeds have also been used for thermal ablation of locally recurrent disease at our institution3 and by others.5 Further heating techniques that have been evaluated as salvage therapies for local failure following radiation of prostate cancer include interstitial microwave thermotherapy, radio frequency interstitial tumor ablation and transrectal high intensity focused ultrasonography.6 – 8 Respectfully, Manfred Johannsen, Stefan A. Loening and Serdar Deger Department of Urology-Campus Mitte Charite´ University Medicine Schumannstr. 20 –21 10117 Berlin Germany e-mail: [email protected] 1. Johannsen, M., Jordan, A., Scholz, R., Koch, M., Lein, M., Deger, S. et al: Evaluation of magnetic fluid hyperthermia in a standard rat model of prostate cancer. J Endourol, 18: 495, 2004 2. Johannsen, M., Thiesen, B., Jordan, A., Taymoorian, K., Gneveckow, U., Waldofner, N. et al: Magnetic fluid hyperthermia (MFH) reduces prostate cancer growth in the orthotopic Dunning R3327 rat model. Prostate, [Epub ahead of print], 2005 3. Johannsen, M., Gneveckow, U., Eckelt, L., Feussner, A., Waldo¨fner, N., Scholz, R. et al: Clinical hyperthermia of prostate cancer using magnetic nanoparticles—presentation of a new interstitial technique. Unpublished data 4. Deger, S., Taymoorian, K., Boehmer, D., Schink, T., Roigas, J., Wille, A. H. et al: Thermoradiotherapy using interstitial selfregulating thermoseeds: an intermediate analysis of a phase II trial. Eur Urol, 45: 574, 2004 5. Master, V. A., Shinohara, K. and Carroll, P. R.: Ferromagnetic thermal ablation of locally recurrent prostate cancer: prostate specific antigen results and immediate/intermediate morbidities. J Urol, 172: 2197, 2004 6. Sherar, M. D., Gertner, M. R., Yue, C. K. K., O’Malley, M. E., Toi, A., Gladman, A. S. et al: Interstitial microwave thermal therapy for prostate cancer: method of treatment and results of a
Vol. 174, 1151–1156, September 2005 Printed in U.S.A.
Letters to the Editor/Errata RE: BACILLUS CALMETTE-GUERIN VERSUS EPIRUBICIN FOR PRIMARY, SECONDARY OR CONCURRENT CARCINOMA IN SITU OF THE BLADDER: RESULTS OF A EUROPEAN ORGANIZATION FOR THE RESEARCH AND TREATMENT OF CANCER–GENITO-URINARY GROUP PHASE III TRIAL (30906)
2. Freedman, L. S. and White, S. J.: On the use of Pocock and Simon’s method for balancing treatment numbers over prognostic factors in the controlled clinical trial. Biometrics, 32: 691, 1976 DOI: 10.1097/01.ju.0000169425.93927.7a
T. M. de Reijke, K. H. Kurth, R. J. Sylvester, R. R. Hall, M. Brausi, K. van de Beek, K. E. J. Landsoght, P. Carpentier and Members of the European Organization for the Research and Treatment of Cancer-Genito-Urinary Group
RE: PROGNOSIS OF PATIENTS WITH LYMPH NODE POSITIVE PROSTATE CANCER FOLLOWING RADICAL PROSTATECTOMY: LONG-TERM RESULTS
J Urol, 173: 405– 409, 2005 To the Editor. We read this article with interest, and would like the authors to comment on several topics. The study uses complete response rate as the primary outcome for the sample size calculation. If ␣ ⫽ 0.1, 1 ⫺  ⫽ 0.8, P0 ⫽ 80%, effect size (P0 ⫺ P1) ⫽ 15%, using the popular formula for calculating sample size, N ⫽ 147 (per group). Also, using available computer software such as PS, Power and Sample Size Calculation, version 2.1.31 (Vanderbilt University Medical Center, Nashville, Tennessee), we obtained 109 samples per study arm, which is different from the 65 samples per study arm in the article. In addition, the patients were selected from 28 institutions in several European countries. Which method was used to generate random allocation sequence or to implement allocation concealment? Finally, the study was designed for analysis by intent to treat principle. In the results section the authors state, “Because 130 evaluable patients were required, 168 were entered to compensate for ineligible patients and those in whom the response to treatment could not be assessed due to absent followup biopsies.” This statement seems to contradict the intent to treat analysis principle. Respectfully, Darab Mehraban and Fatemeh Esfahani Urology Section Dr. Shariati Hospital Tehran University of Medical Sciences Tehran, Iran
Reply by Authors. Concerning the sample size calculation, the equation given by Mehraban and Esfahani is correct when testing for a difference in response rates. For a 2-sided test using ␣ ⫽ 0.10, Z1-␣/2 ⫽ 1.645. For a power of 80%, Z1- ⫽ 0.842 and N ⫽ 109. For a power of 90%, Z1- ⫽ 1.282 and N ⫽ 150. These are the figures quoted in the letter. However, this same equation cannot be used for testing noninferiority, since as stated in the article, the null hypothesis is no longer “no difference” in response rates. The correct formula is given by Blackwelder:1
S. Daneshmand, M. L. Quek, J. P. Stein, G. Lieskovsky, J. Cai, J. Pinski, E. C. Skinner and D. G. Skinner J Urol, 172: 2252–2255, 2004 To the Editor. This interesting article adds clarity to an important issue. The incidence of lymph node metastases is approximately 5% in current series of clinically localized prostate cancer.1, 2 This rate may reflect earlier detection of the disease due to widespread prostate specific antigen (PSA) testing and a limitation of standard lymph node dissection. In fact, in recent studies more extended lymphadenectomy has been proposed to obtain more accurate staging3 or even a possible chance of cure.4 Of course, extended dissection yields a higher number of lymph nodes, as studies comparing extended dissection to standard dissection have revealed.1– 4 However, some facts deserve attention. The number of positive lymph nodes does not reach a statistically significant difference regardless of the type of dissection that is carried out, as reported in randomized studies.5, 6 Ample variation exists in the number of lymph nodes that can be obtained at lymphadenectomy, and depends on several factors, namely anatomical boundaries, en bloc or separate removal, thickness and number of sections examined by the pathologist, lymph node biology and lack of a “routine” pattern of lymphatic spread.1, 7–9 The percentage of positive nodes demonstrates only a weak association with the total number, as illustrated in the figure. Conversely, the percentage of positive nodes depends on the extent of local disease (ie pathological tumor stage category),4 and average tumor volume (average tumor volume in this study was 2.3 cc overall and 10.9 cc for the node positive group).5 In a multivariate analysis the percentage of positive nodes (ie 15% or greater) together with a Gleason prostatectomy score of 8 to 10 and seminal vesicle invasion appeared to predict PSA progression in node positive cases.2 It appears clear that by extending the boundaries of lymph node dissection a higher proportion of cases of smaller volume disease can be detected. However, it should be emphasized that the benefit that can be observed in PSA progression-free survival is likely the consequence of reduced tumor burden rather than simply the effect of
共 Z 1-␣⫹Z1-)2[P0(1⫺P0)⫹P1(1⫺P1)]/(P0⫺P1⫺␦)2. In our case Z1-␣ ⫽ Z0.90 ⫽ 1.282, Z1- ⫽ Z0.80 ⫽ 0.842, P0 ⫽ P1 ⫽ 0.80 and ␦ ⫽ 0.15. This equation yields N ⫽ 65 patients in each group. Investigators had to contact the European Organization for the Research and Treatment of Cancer Data Center by telephone or the Internet to register and randomize patients. Patients were centrally randomized using the minimization technique, with stratification for institution, type of carcinoma in situ (primary, secondary, concurrent) and number of biopsies with carcinoma in situ (1, more than 1).2 Following the intent to treat principle all 168 randomized patients were included in the analyses. Since 33 patients could not be assessed for response to treatment, their inclusion in the analysis could dilute the size of any treatment difference that might exist. As the goal was to try to show that there was no difference in complete response rates, 38 additional patients were entered in an effort not to underestimate the size of any potential treatment difference. 1. Blackwelder, W. C.: “Proving the null hypothesis” in clinical trials. Control Clin Trials, 3: 345, 1982 1151
Numbers in graph indicate studies as they are listed in references
1152
LETTERS TO THE EDITOR
lymph node removal. Furthermore, extended dissection is associated with a higher incidence of surgical complications.3– 6 Respectfully, Massimo Maffezzini Struttura Complessa di Urologia Ospedale Galliera Mura delle Cappuccine 14 16128 Genova, Italy
Reply by Authors. We agree that there is great variation in the boundaries of pelvic lymph node dissection and the reported number of positive lymph nodes obtained at lymphadenectomy. The percentage of positive lymph nodes is dependent on the number of lymph nodes obtained, and, therefore, is a reflection of the extent of lymph node dissection. Bader et al reported that extending lymph node dissection to the internal iliac nodes not only yields more lymph nodes, but also yields positive nodes that would otherwise have been missed in a standard lymph node dissection.10 In their series 19% of patients had positive lymph nodes in the internal iliac lymph node chain only. The average number of lymph nodes obtained in their series was 21, similar to our node count of 19. Allaf et al from the Johns Hopkins group also found that extended lymph node dissection not only removed more lymph nodes, but also detected more lymph node positive disease (3.2% vs 1.1%, p ⬍0.0001) than the more anatomically limited technique.1 This finding held true for patients across all pathological subgroups. The complication rate in these series, including ours, is low and comparable to the more limited lymph node dissection technique. Conversely, Clark et al performed a randomized study that compared standard lymph node dissection to extended lymph node dissection on the contralateral side in the same patient.5 Extended lymph node dissection included the external iliac nodes to a point above the bifurcation of the common iliac artery, the obturator nodes and the presacral nodes. There was no difference observed in the incidence of positive lymph nodes in extended lymph node dissection. Perhaps a difference would have been observed if the internal iliac nodes had been included in the extended dissection. Numerous studies have shown that patients with a limited number of positive lymph nodes in fact have longer survival than those with more lymph node involvement, similar to radical cystectomy series.4, 10 –12 By reporting the absolute number of positive lymph nodes as well as the positive lymph node density (LND) we attempted to clarify the extent of disease in the lymph nodes. Having 1 positive node from a total of 4 (LND 25%) is a different clinical scenario than having 2 positive nodes from a total of 20 (LND 10%). We agree that reduced tumor burden (T stage) has a significant impact on progression-free survival. However, we believe that the removal of limited (1 or 2) positive lymph nodes serves as an independent prognostic factor and may offer long-term survival. REFERENCES
1. Allaf, M. E., Palapattu, G. S., Trock, B. J., Carter, H. B. and Walsh, P. C.: Anatomical extent of lymph node dissection: impact on men with clinically localized prostate cancer. J Urol, 172: 1840, 2004 2. Palapattu, G. S., Allaf, M. E., Trock, B. J., Epstein, J. I. and Walsh, P. C.: Prostate specific antigen progression in men with lymph node metastases following radical prostatectomy: results of long-term followup. J Urol, 172: 1860, 2004 3. Heidendreich, A., Varga, Z. and Knobloch, R.: Extended pelvic lymphadenectomy in patients undergoing radical prostatectomy: high incidence of lymph node metastasis. J Urol, 167: 1681, 2002 4. Bader, P., Burkhard, F. C., Markwalder, R. and Studer, U. E.: Disease progression and survival of patients with positive lymph nodes after radical prostatectomy. Is there a chance of cure? J Urol, 169: 849, 2003 5. Clark, T., Parekh, D. J., Cookson, M. S., Chang, S. S., Smith, E. R., Jr., Wells, N. et al: Randomized prospective evaluation of extended versus limited lymph node dissection in patients with clinically localized prostate cancer. J Urol, 169: 145, 2003 6. Stone, N. N., Stock, R. G. and Unger, P.: Laparoscopic pelvic lymph node dissection for prostate cancer: comparison of the extended and modified techniques. J Urol, 158: 1891, 1997 7. Bochner, B. H., Herr, H. W. and Reuter, V. E.: Impact of separate versus en bloc pelvic lymph node dissection on the number of
lymph nodes retrieved in cystectomy specimens. J Urol, 166: 2295, 2001 8. McLaughlin, A. P., Saltzstein, S. L., McCullough, D. L. and Gittes, R. F.: Prostatic carcinoma: incidence and location of unsuspected lymphatic metastases. J Urol, 115: 89, 1976 9. Wawroschek, F., Vogt, H., Weckermann, D., Wagner, T., Hamm, M. and Harzmann, R.: Radioisotope guided pelvic lymph node dissection for prostate cancer. J Urol, 166: 1715, 2001 10. Bader, P., Burkhard, F. C., Markwalder, R. and Studer, U. E.: Is a limited lymph node dissection an adequate staging procedure for prostate cancer? J Urol, 168: 514, 2002 11. Cheng, L., Zincke, H., Blute, M. L., Bergstralh, E. J., Scherer, B. and Bostwick, D. G.: Risk of prostate carcinoma death in patients with lymph node metastasis. Cancer, 91: 66, 2001 12. Frazier, H. A., 2nd, Robertson, J. E. and Paulson, D. F.: Does radical prostatectomy in the presence of positive pelvic lymph nodes enhance survival? World J Urol, 12: 308,1994 DOI: 10.1097/01.ju.0000169157.74608.3a
RE: CURRENT STATUS OF LOCAL SALVAGE THERAPIES FOLLOWING RADIATION FAILURE FOR PROSTATE CANCER N. J. Touma, J. I. Izawa and J. L. Chin J Urol, 173: 373–379, 2005 To the Editor. The authors provide an overview of treatment options after local failure following radiation therapy of localized prostate cancer. In this regard we would like to add our experience with thermal ablation techniques, which may also be used to treat local recurrence of localized prostate cancer. Magnetically mediated heating of iron oxide nanoparticles is a novel treatment approach that has been evaluated in animal models, including prostate cancer.1 Using this nanotechnology, temperatures of up to 70C can be achieved in the prostate during exposure to an alternating current magnetic field.2 At our institution thermotherapy using magnetic nanoparticles is currently being evaluated in patients with local failure following radiation therapy for prostate cancer. From our initial experience this approach is feasible and well tolerated.3 We have previously evaluated ferromagnetic seeds for thermotherapy of prostate cancer in combination with irradiation.4 These temperature self-regulating seeds have also been used for thermal ablation of locally recurrent disease at our institution3 and by others.5 Further heating techniques that have been evaluated as salvage therapies for local failure following radiation of prostate cancer include interstitial microwave thermotherapy, radio frequency interstitial tumor ablation and transrectal high intensity focused ultrasonography.6 – 8 Respectfully, Manfred Johannsen, Stefan A. Loening and Serdar Deger Department of Urology-Campus Mitte Charite´ University Medicine Schumannstr. 20 –21 10117 Berlin Germany e-mail: [email protected] 1. Johannsen, M., Jordan, A., Scholz, R., Koch, M., Lein, M., Deger, S. et al: Evaluation of magnetic fluid hyperthermia in a standard rat model of prostate cancer. J Endourol, 18: 495, 2004 2. Johannsen, M., Thiesen, B., Jordan, A., Taymoorian, K., Gneveckow, U., Waldofner, N. et al: Magnetic fluid hyperthermia (MFH) reduces prostate cancer growth in the orthotopic Dunning R3327 rat model. Prostate, [Epub ahead of print], 2005 3. Johannsen, M., Gneveckow, U., Eckelt, L., Feussner, A., Waldo¨fner, N., Scholz, R. et al: Clinical hyperthermia of prostate cancer using magnetic nanoparticles—presentation of a new interstitial technique. Unpublished data 4. Deger, S., Taymoorian, K., Boehmer, D., Schink, T., Roigas, J., Wille, A. H. et al: Thermoradiotherapy using interstitial selfregulating thermoseeds: an intermediate analysis of a phase II trial. Eur Urol, 45: 574, 2004 5. Master, V. A., Shinohara, K. and Carroll, P. R.: Ferromagnetic thermal ablation of locally recurrent prostate cancer: prostate specific antigen results and immediate/intermediate morbidities. J Urol, 172: 2197, 2004 6. Sherar, M. D., Gertner, M. R., Yue, C. K. K., O’Malley, M. E., Toi, A., Gladman, A. S. et al: Interstitial microwave thermal therapy for prostate cancer: method of treatment and results of a