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RE: EXTENDED RADICAL LYMPHADENECTOMY IN PATIENTS WITH UROTHELIAL BLADDER CANCER: RESULTS OF A PROSPECTIVE MULTICENTER STUDY
0022-5347/04/1721-0386/0 THE JOURNAL OF UROLOGY® Copyright © 2004 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 172, 386 –389, July 2004 Printed in U.S.A.
Letters to the Editor/Errata RE: EXTENDED RADICAL LYMPHADENECTOMY IN PATIENTS WITH UROTHELIAL BLADDER CANCER: RESULTS OF A PROSPECTIVE MULTICENTER STUDY J. Leissner, M. A. Ghoneim, H. Abol-Enein, J. W. Thu¨roff, L. Franzaring, M. Fisch, H. Schulze, G. Managadze, E. P. Allhoff, M. A. El-Baz, H. Kastendieck, P. Buhtz, S. Kropf, R. Hohenfellner and H. K. Wolf J Urol, 171: 139 –144, 2004 To the Editor. We would like to congratulate the authors on their large prospective study describing the detailed distribution of nodal metastases in patients with urothelial bladder cancer. However, we disagree with some of the conclusions presented based on their findings. The idea of curative lymph node dissection for cancer was initiated by Halsted more than 100 years ago. Since then, there has been vast improvement in the knowledge of the biology of dissemination of malignant cells based on laboratory studies. Often regional lymph node metastases and microscopic distant metastases occur simultaneously. In clinical research retrospective series like that of Halsted have been challenged by prospective controlled trials evaluating a possible survival benefit with extended node dissection. Large multicenter trials of breast and gastric cancers did not show any benefit with this approach.1, 2 Similarly, this approach also has to be tested in a controlled fashion for urothelial bladder cancer before a positive correlation between postoperative survival and the extent of the procedure can be verified. If the aim solely is to have correct nodal staging, we agree with the authors that limited dissection is insufficient. This finding was also evident in our trial assessing the sentinel node concept, presented earlier in this journal.3 How one can discard this concept based on the findings of the authors is not logical. The original sentinel node concept was first described by Gould et al4 in a cancer of the parotid gland and clinically implemented by Cabanas in penile carcinoma.5 They proposed that the lymphatic drainage from a primary tumor goes to one particular regional lymph node called the sentinel node and then continues to other nodes. The tumor status of the sentinel node was believed to reflect the status of the regional lymphatic field. More than 10 years ago that concept evolved, and based on dynamic investigations of lymphatic drainage in each patient, it was clearly shown that the site of the sentinel node(s) was specific for each individual.6 Our study suggested a similar unique lymphatic drainage in urothelial bladder cancer. The findings of single lymph node metastases widely distributed in the pelvis also fit well with this view. Today, investigation of lymphatic drainage and preoperative identification of sentinel node(s) is part of regular treatment in malignant melanoma and breast cancer. Whether the sentinel node concept is also applicable in routine treatment for bladder cancer, as indicated in our pilot trial, is currently being tested in a large prospective multicenter trial. The value thereof eventually has to be tested in future randomized trials. Respectfully, Per-Uno Malmstro¨m and Amir Sherif Department of Urology Uppsala University Hospital Uppsala, Sweden and Magnus Tho¨rn Department of Surgery South Stockholm General Hospital Stockholm, Sweden 1. Bonenkamp, J. J., Hermans, J., Sasako, M. and van de Velde, C. J.: Extended lymph-node dissection for gastric cancer. Dutch Gastric Cancer Group. N Engl J Med, 340: 908, 1999 2. Veronesi, U., Cascinelli, N., Mariani, L., Greco, M., Saccozzi, R., Luini, A. et al: Twenty-year follow-up of a randomized study
386
3. 4. 5. 6.
comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med, 347: 1227, 2002 Sherif, A., De La Torre, M., Malmstro¨m, P.-U. and Tho¨rn, M.: Lymphatic mapping and detection of sentinel nodes in patients with bladder cancer. J Urol, 166: 812, 2001 Gould, E. A., Winship, T., Philbin, P. H. and Kerr, H. H.: Observations on a “sentinel node” in cancer of the parotid. Cancer, 13: 77, 1960 Cabanas, R. M.: An approach for the treatment of penile carcinoma. Cancer, 39: 456, 1977 Morton, D. L., Wen, D. R., Wong, J. H., Economou, J. S., Cagle, L. A., Storm, F. K. et al: Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg, 127: 392, 1992
Reply by Authors. We agree with Malmstro¨m et al that our knowledge regarding the curative effect of lymph node dissection is still minimal. We also have already initiated a prospective multicenter study to evaluate the effect of extensive lymph node dissection on survival. However, some of the literature presented by the authors should be looked at carefully. The study of lymph node dissection for gastric cancer (there is another comparable study published by Cuschieri et al1) has some severe logistical failures—the compliance of surgeons was as low as 60%, and some centers performed only 1 to 2 operations per year. In addition, a subgroup of patients with organ confined tumors had a benefit from extended lymph node dissection. In the surgical literature the value of extended lymph node dissection is still questionable even after these 2 studies. Whether the concept of the sentinel node can be transferred to bladder cancer is still an open question. The main aim of this concept is to decrease operative morbidity if no positive lymph node can be detected with the sentinel node techniques. Because axillary lymph node dissection is associated with high morbidity, it has been introduced in the operative therapy of breast cancers. The same is true for inguinal lymph node dissection for penile cancer. However, this concept is still questionable in the gynecological literature and it should be performed only in clinical trials. We believe this concept should not be transferred to invasive bladder cancer. Retrospective studies have demonstrated that even patients with up to 5 positive lymph nodes may benefit from extensive and radical surgery. One would never identify all positive lymph nodes with the sentinel node technique. Why should we decrease the prognosis in our patients by a limited surgical technique when there is a chance of cure? Similarly, this concept has no place in the surgery of cervical and endometrial cancers. 1. Cuschieri, A., Weeden, S., Fielding, J., Bancewicz, J., Craven, J., Joypaul, V. et al: Patient survival after D1 and D2 resections for gastric cancer: long-term results of the MRC randomized surgical trial. Surgical Co-operative Group. Br J Cancer, 79: 1522, 1999 DOI: 10.1097/01.ju.0000132366.20760.53
RE: NO INCREASED PROSTATE CANCER INCIDENCE AFTER NEGATIVE TRANSRECTAL ULTRASOUND GUIDED MULTIPLE BIOPSIES IN MEN WITH INCREASED PROSTATE SPECIFIC ANTIGEN AND/OR ABNORMAL DIGITAL RECTAL EXAMINATION A. Bill-Axelson, L. Holmberg, B. Norle´n, C. Busch and M. Norberg J Urol, 170: 1180 –1183, 2003 To the Editor. The authors concluded that men with negative prostate biopsies after an extended protocol performed for increased prostate specific antigen and/or abnormal digital rectal examination have no increased incidence of prostate cancer at 6 years of followup compared with an age matched, standardized male population. How-
Vol. 172, 386 –389, July 2004 Printed in U.S.A.
Letters to the Editor/Errata RE: EXTENDED RADICAL LYMPHADENECTOMY IN PATIENTS WITH UROTHELIAL BLADDER CANCER: RESULTS OF A PROSPECTIVE MULTICENTER STUDY J. Leissner, M. A. Ghoneim, H. Abol-Enein, J. W. Thu¨roff, L. Franzaring, M. Fisch, H. Schulze, G. Managadze, E. P. Allhoff, M. A. El-Baz, H. Kastendieck, P. Buhtz, S. Kropf, R. Hohenfellner and H. K. Wolf J Urol, 171: 139 –144, 2004 To the Editor. We would like to congratulate the authors on their large prospective study describing the detailed distribution of nodal metastases in patients with urothelial bladder cancer. However, we disagree with some of the conclusions presented based on their findings. The idea of curative lymph node dissection for cancer was initiated by Halsted more than 100 years ago. Since then, there has been vast improvement in the knowledge of the biology of dissemination of malignant cells based on laboratory studies. Often regional lymph node metastases and microscopic distant metastases occur simultaneously. In clinical research retrospective series like that of Halsted have been challenged by prospective controlled trials evaluating a possible survival benefit with extended node dissection. Large multicenter trials of breast and gastric cancers did not show any benefit with this approach.1, 2 Similarly, this approach also has to be tested in a controlled fashion for urothelial bladder cancer before a positive correlation between postoperative survival and the extent of the procedure can be verified. If the aim solely is to have correct nodal staging, we agree with the authors that limited dissection is insufficient. This finding was also evident in our trial assessing the sentinel node concept, presented earlier in this journal.3 How one can discard this concept based on the findings of the authors is not logical. The original sentinel node concept was first described by Gould et al4 in a cancer of the parotid gland and clinically implemented by Cabanas in penile carcinoma.5 They proposed that the lymphatic drainage from a primary tumor goes to one particular regional lymph node called the sentinel node and then continues to other nodes. The tumor status of the sentinel node was believed to reflect the status of the regional lymphatic field. More than 10 years ago that concept evolved, and based on dynamic investigations of lymphatic drainage in each patient, it was clearly shown that the site of the sentinel node(s) was specific for each individual.6 Our study suggested a similar unique lymphatic drainage in urothelial bladder cancer. The findings of single lymph node metastases widely distributed in the pelvis also fit well with this view. Today, investigation of lymphatic drainage and preoperative identification of sentinel node(s) is part of regular treatment in malignant melanoma and breast cancer. Whether the sentinel node concept is also applicable in routine treatment for bladder cancer, as indicated in our pilot trial, is currently being tested in a large prospective multicenter trial. The value thereof eventually has to be tested in future randomized trials. Respectfully, Per-Uno Malmstro¨m and Amir Sherif Department of Urology Uppsala University Hospital Uppsala, Sweden and Magnus Tho¨rn Department of Surgery South Stockholm General Hospital Stockholm, Sweden 1. Bonenkamp, J. J., Hermans, J., Sasako, M. and van de Velde, C. J.: Extended lymph-node dissection for gastric cancer. Dutch Gastric Cancer Group. N Engl J Med, 340: 908, 1999 2. Veronesi, U., Cascinelli, N., Mariani, L., Greco, M., Saccozzi, R., Luini, A. et al: Twenty-year follow-up of a randomized study
386
3. 4. 5. 6.
comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med, 347: 1227, 2002 Sherif, A., De La Torre, M., Malmstro¨m, P.-U. and Tho¨rn, M.: Lymphatic mapping and detection of sentinel nodes in patients with bladder cancer. J Urol, 166: 812, 2001 Gould, E. A., Winship, T., Philbin, P. H. and Kerr, H. H.: Observations on a “sentinel node” in cancer of the parotid. Cancer, 13: 77, 1960 Cabanas, R. M.: An approach for the treatment of penile carcinoma. Cancer, 39: 456, 1977 Morton, D. L., Wen, D. R., Wong, J. H., Economou, J. S., Cagle, L. A., Storm, F. K. et al: Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg, 127: 392, 1992
Reply by Authors. We agree with Malmstro¨m et al that our knowledge regarding the curative effect of lymph node dissection is still minimal. We also have already initiated a prospective multicenter study to evaluate the effect of extensive lymph node dissection on survival. However, some of the literature presented by the authors should be looked at carefully. The study of lymph node dissection for gastric cancer (there is another comparable study published by Cuschieri et al1) has some severe logistical failures—the compliance of surgeons was as low as 60%, and some centers performed only 1 to 2 operations per year. In addition, a subgroup of patients with organ confined tumors had a benefit from extended lymph node dissection. In the surgical literature the value of extended lymph node dissection is still questionable even after these 2 studies. Whether the concept of the sentinel node can be transferred to bladder cancer is still an open question. The main aim of this concept is to decrease operative morbidity if no positive lymph node can be detected with the sentinel node techniques. Because axillary lymph node dissection is associated with high morbidity, it has been introduced in the operative therapy of breast cancers. The same is true for inguinal lymph node dissection for penile cancer. However, this concept is still questionable in the gynecological literature and it should be performed only in clinical trials. We believe this concept should not be transferred to invasive bladder cancer. Retrospective studies have demonstrated that even patients with up to 5 positive lymph nodes may benefit from extensive and radical surgery. One would never identify all positive lymph nodes with the sentinel node technique. Why should we decrease the prognosis in our patients by a limited surgical technique when there is a chance of cure? Similarly, this concept has no place in the surgery of cervical and endometrial cancers. 1. Cuschieri, A., Weeden, S., Fielding, J., Bancewicz, J., Craven, J., Joypaul, V. et al: Patient survival after D1 and D2 resections for gastric cancer: long-term results of the MRC randomized surgical trial. Surgical Co-operative Group. Br J Cancer, 79: 1522, 1999 DOI: 10.1097/01.ju.0000132366.20760.53
RE: NO INCREASED PROSTATE CANCER INCIDENCE AFTER NEGATIVE TRANSRECTAL ULTRASOUND GUIDED MULTIPLE BIOPSIES IN MEN WITH INCREASED PROSTATE SPECIFIC ANTIGEN AND/OR ABNORMAL DIGITAL RECTAL EXAMINATION A. Bill-Axelson, L. Holmberg, B. Norle´n, C. Busch and M. Norberg J Urol, 170: 1180 –1183, 2003 To the Editor. The authors concluded that men with negative prostate biopsies after an extended protocol performed for increased prostate specific antigen and/or abnormal digital rectal examination have no increased incidence of prostate cancer at 6 years of followup compared with an age matched, standardized male population. How-