- Email: [email protected]
Reply to Magdi Kirollos’ Letter to the Editor re: Axel Heidenreich, Gunnar Aus, Michel Bolla et al. EAU Guidelines on Prostate Cancer. Eur Urol 2008;53:68–80
695
european urology 54 (2008) 692–700
[6] Wiley Interscience Web page. Available at: http://www. interscience.wiley.com/cochrane/clsysrev/articles/ CD004720/pdf_fs.html. Magdi Kirollos* South Devon Healthcare Foundation Trust, Urology Department Torbay Hospital, Lawes Brigde, Torquay, Devon, TQ2 7AA, UK
*Tel. +44 1803655282 E-mail address: [email protected] March 4, 2008 Published online ahead of print on March 18, 2008 doi:10.1016/j.eururo.2008.03.002
DOI of original article: 10.1016/j.eururo.2007.09.002
Reply to Magdi Kirollos’ Letter to the Editor re: Axel Heidenreich, Gunnar Aus, Michel Bolla et al. EAU Guidelines on Prostate Cancer. Eur Urol 2008;53:68–80 We are very grateful for the valuable comments made by Kirollos [1], considering the great importance and influence of these guidelines with regard to diagnosis and therapy of patients with prostate cancer in Europe. Certainly the constructive criticism will be considered in the updated version of EAU guidelines, which will be presented in 2009. The new version of the guidelines has been developed on the basis of the older version and with the help of consultant radio-oncologists, medical oncologists, and, last but not least, the peer review board of European Urology, underlining the fact that these guidelines have undergone extensive consultation processes prior to publication [2]. The published version of the guidelines, however, represents the short version, which had to be significantly shortened because of space limitations, as compared to the long version accessible via the Internet [3]. Therefore, various recommendations had to be condensed extensively without the opportunity to discuss individual approaches; it was the purpose of the included tables to provide the reader with some additional information. However, we agree with Dr. Kirollos that we should have been even more careful when writing and phrasing the short version of the EAU guidelines on prostate cancer. The authors are correct in asking for clarification of prostate cancer (PCA) grading in biopsy specimens with cancer present in <5% of the samples. It is correct that the worst grade should always be included, even if present in <5%. However, it is also common knowledge that the prognostic significance of such small foci of PCA is unreliable and that therapeutic recommendations based on such limited information should most probably be based on a second biopsy.
Active surveillance and watchful waiting are used in the EAU guidelines, reflecting different stages of PCA and different purposes of therapy. It becomes clear from the introductory sentence that the term ‘‘watchful waiting’’ is used to describe a treatment strategy that includes an active standpoint to postpone treatment until it is required. Active surveillance, however, has emerged as a true therapeutic alternative in men with PCA and a low risk of disease progression based on the high 20year PCA specific survival rates. We should have given a more precise definition when referring to further therapy: active surveillance is a clear therapeutic option for low-risk PCA, whereas watchful waiting is reserved for patients with advanced PCA when treatment is not delivered for curative intent. The data and the opinions given by the Cochrane review had been included in the EAU guidelines. With regard to the indication for prostate biopsy, we clearly have focused on the fact that there is no optimum prostate-specific antigen (PSA) threshold; therefore, the most reliable indicators such as PSA, percentage of free PCA, and PSA velocity have been included, in accordance with other published guidelines. We also have given the recommendation that values of 2.5–3.0 ng/ml should be used as a cut-off in younger men for performing a prostate biopsy. Basically, the indication for the detection of PCA needs a thorough discussion with the patient, independent of the PSA level. Local anesthesia was not considered to be a standard procedure in every single patient, although the results of most of the 23 published studies demonstrated some benefit with regard to biopsyassociated pain, since the results were not highly statistically significant and because there was a wide variation of the techniques used for periprostatic infiltration. Higher complication rates for interstitial brachytherapy have been reported consistently in most studies published to date. With regard to radical prostatectomy, however, a negative impact of
696
european urology 54 (2008) 692–700
previous transurethral resection of the prostate (TURP) has been shown for the laparoscopic approach only, whereas the open surgical approach might be surgically more challenging but there are no negative consequences on functional and oncologic outcomes. Active surveillance still is an option for very wellselected patients with clinically localized, smallvolume PCA and a limited life expectancy. The treatment decision is based primarily on the biopsy findings which—as we all know—are less predictable if not performed according to a well-defined standard. Reflecting the data of different retrospective analyses of guidelines compliance with regard to the performance and histopathologic analysis of prostate biopsies, we felt that a more stringent recommendation on the use of active surveillance would be best considering the high variability of the quality of prostate biopsies in Europe. We have extensively discussed the data of the prospective randomized trial ‘‘Radical prostatectomy versus watchful waiting’’ in the long version of the EAU guidelines, considering all the concerns raised by Dr. Kirollos. Extensive discussion of the pros and cons of nerve-sparing radical prostatectomy was not possible in the short version, owing simply to space limitations. However, there are no drawbacks of the nerve-sparing procedures: the functional outcome with regard to potency and continence is improved; the oncologic outcome is not harmed. The overall survival rates are given in the long version of the guidelines and the issue of radical prostatectomy in locally advanced disease is discussed extensively. The rationale for pelvic lymphadenectomy is not only cure but also adequate staging of the pelvic lymph nodes. Therefore, anatomic pelvic lymphadenectomy should always be performed in men with a higher likelihood of harbouring lymph node metastases in order to trigger individualized adjuvant therapeutic options. It was the aim of the short version of the guidelines to report the indications and the outcomes of the various treatment options for prostate cancer. Therefore, the different techniques of radiation oncology available nowadays have been described in the text. We have not included the newer variants such as intensity-modulated radiation therapy IMRT or high-dose radiation (HDR) brachytherapy, since the long-term data for the former are not available and there are no prospective randomized trials available demonstrating that HDR brachytherapy is superior to HDR therapy. This issue, however, is discussed in more detail in the long version of the manuscript.
With regard to cryosurgery, its potential role as salvage treatment is mentioned in Table 7. With regard to high-intensity focused ultrasound (HIFU), too few data with a too short follow-up are available to clearly define its role as an effective secondary treatment option with curative intent. The misprintings in section 11.3.3.3 in the long version have been corrected. The use of bisphosphonates has not been discussed in extensive detail with regard to the prevention of osteoporosis following androgendeprivation therapy for various reasons. There are small prospective clinical phase 2 trials available demonstrating a benefit of bisphosphonates to prevent osteoporosis. However, there are no clinical phase 3 trials, there is no Food and Drug Administration (FDA) approval with regard to the amino bisphosphonates, and there are no data available indicating that simple prophylactic measures such as sports, calcium, and vitamin D supplementation would be equivalent, as has been shown in patients with osteopenia. Again we would like to thank Dr. Kirollos for the valuable and constructive comments, which will help to further improve the next version of the guidelines.
Conflicts of interest Prof. Dr. Med. Axel Heidenreich has financial relationships as lecturer, consultant, and Advisory Board Member at Amgen, Ferring, Sanofi-Aventis, Novartis, Hoffmann-La Roche, Centocor, Astra Zeneca, and Ipsen Pharma. During the EAU meeting in Berlin, 2007, Prof. Gunnar Aus took part in a symposium related to high-intensity focused ultrasound (HIFU) for the treatment of prostate cancer. For chairing this symposium, he received financial compensation from EDAP, Lyon, France. There are no financial disclosures to be made for Prof. Bolla, Dr. Steven Joniau, Prof. V.B. Matveev, Prof. Hans Peter Schmid, or Prof. Filliberto Zattoni. References [1] Kirollos M. Re: Axel Heidenreich, Gunnar Aus, Michel Bolla et al. EAU guidelines on prostate cancer. Eur Urol 2008;53:68–80. [2] Heidenreich A, Aus G, Bolla M, Jonieau S, Matveev VB, Schmid HP, Zattoni F. EAU guidelines on prostate cancer. Eur Urol 2008;53:68–80. [3] http://www.uroweb.org/nc/professional-resources/guidelines/online/.
european urology 54 (2008) 692–700
Axel Heidenreich* University of Cologne, Cologne, Germany *Tel. +49 0221 478 87636; Fax: +49 0221 478 87901 E-mail address: [email protected]
697
April 9, 2008 Published online ahead of print on April 21, 2008 doi:10.1016/j.eururo.2008.04.034
DOIs of original articles: 10.1016/j.eururo.2007.09.002, 10.1016/j.eururo.2008.03.002
Re: Gunnar Wendt-Nordahl, Stephanie Huckele, Patrick Honeck, et al. 980-nm Diode Laser: A Novel Laser Technology for Vaporization of the Prostate. Eur Urol 2007;52:1723–8 We read with great interest the article by WendtNordahl et al [1] describing the ablation and coagulation properties of the diode laser device with an emission wavelength of 980 nm. However, the title of this article, ‘‘980-nm Diode Laser: A Novel Laser Technology for Vaporization of the Prostate,’’ is misleading. Although it suggests a novel treatment option for benign prostatic hyperplasia (BPH), the article merely describes studies with an ex vivo blood-perfused porcine kidney model. In this ex vivo model, a coagulation zone between 208.8 30.8 mm and 255 28.2 mm at a generator output power level of 100 W in the pulsed- and continuous-wave mode was observed. These results are similar to coagulation zones described for transurethral resection of the prostate (TURP) in the same manuscript. In a comparable experimental setting, our study group observed a mean coagulation zone of 10.2 1.07 mm for the 980 nm diode laser, indicating an approximately 50 deeper tissue penetration [2]. Only a limited number of original articles in current literature deal with in vivo diode laser treatment at 980 nm. In an in vivo porcine model, Ogan et al observed at 23 W (pulsed mode on-time 0.05 s; off-time 0.03 s) coagulation zones of 3 to 5 mm when performing laparoscopic partial nephrectomy [3]. Another in vivo study on mongrel dogs and diode laser treatment (l = 980 nm) of the gastric wall with 10 W (cw-mode) for 50 to 400 s showed thermal tissue damage between 8 mm (range: 5–11) and 11 mm (range: 8–15), respectively [4]. In conclusion, when one considers (1) laser physical principles, (2) our results in a comparable experimental setting, and (3) the current literature on this issue, the degree of coagulation zones of 208.8 30.8 mm to 255 28.2 mm at 100 W in the pulsed- and continuous-wave described by WendtNordahl et al, at a wavelength of 980 nm, seems rather questionable. The hypothesis that increased DOI of original article: 10.1016/j.eururo.2007.06.029
ablation properties and decreased coagulation depth of diode laser devices in comparison to potassium-titanyl-phosphate (KTP) laser systems may be explained by higher energy absorption of the epithelial surface has to be questioned, because both the optical penetration depth and the ex vivo and in vivo studies contradict this hypothesis. Conclusive verification of tissue ablation and coagulation zone is warranted for in vivo studies on prostate tissue before clinical evaluation of this laser system may be considered. Conflicts of interest: The authors have nothing to disclose.
References [1] Wendt-Nordahl G, Huckele S, Honeck P, et al. 980-nm diode laser: a novel laser technology for vaporization of the prostate. Eur Urol 2007;52:1723–8. [2] Seitz M, Ackermann A, Gratzke C, et al. Diode laser: ex vivo studies on vaporization and coagulation characteristics. Urologe A 2007;46:1242–7. [3] Ogan K, Wilhelm D, Lindberg G, et al. Laparoscopic partial nephrectomy with a diode laser: porcine results. J Endourol 2002;16:749–53. [4] Maema A, Hashimoto D, Yokoya S, Shoji M, Makuuchi M. Spatially selective laser coagulation of the gastric wall: a new methodology. J Surg Res 2002;103:114–20. Michael Seitz* Department of Urology, University Hospital Grosshadern, Ludwig Maximilians University, Munich, Germany Ronald Sroka Laser Laboratory, University Hospital Grosshadern, Ludwig Maximilians University, Munich, Germany *Corresponding author. Urologische Klinik und Poliklinik, Klinikum der Universita¨t, Campus Grosshadern, Ludwig Maximilians Universita¨t, Mu¨nchen, Deutschland. Tel. +49 (0) 89 7095 7741; Fax: +49 (0) 89 7095 4746 E-mail address: [email protected] (M. Seitz) March 6, 2008 Published online ahead of print on March 14, 2008 doi:10.1016/j.eururo.2008.03.005
european urology 54 (2008) 692–700
[6] Wiley Interscience Web page. Available at: http://www. interscience.wiley.com/cochrane/clsysrev/articles/ CD004720/pdf_fs.html. Magdi Kirollos* South Devon Healthcare Foundation Trust, Urology Department Torbay Hospital, Lawes Brigde, Torquay, Devon, TQ2 7AA, UK
*Tel. +44 1803655282 E-mail address: [email protected] March 4, 2008 Published online ahead of print on March 18, 2008 doi:10.1016/j.eururo.2008.03.002
DOI of original article: 10.1016/j.eururo.2007.09.002
Reply to Magdi Kirollos’ Letter to the Editor re: Axel Heidenreich, Gunnar Aus, Michel Bolla et al. EAU Guidelines on Prostate Cancer. Eur Urol 2008;53:68–80 We are very grateful for the valuable comments made by Kirollos [1], considering the great importance and influence of these guidelines with regard to diagnosis and therapy of patients with prostate cancer in Europe. Certainly the constructive criticism will be considered in the updated version of EAU guidelines, which will be presented in 2009. The new version of the guidelines has been developed on the basis of the older version and with the help of consultant radio-oncologists, medical oncologists, and, last but not least, the peer review board of European Urology, underlining the fact that these guidelines have undergone extensive consultation processes prior to publication [2]. The published version of the guidelines, however, represents the short version, which had to be significantly shortened because of space limitations, as compared to the long version accessible via the Internet [3]. Therefore, various recommendations had to be condensed extensively without the opportunity to discuss individual approaches; it was the purpose of the included tables to provide the reader with some additional information. However, we agree with Dr. Kirollos that we should have been even more careful when writing and phrasing the short version of the EAU guidelines on prostate cancer. The authors are correct in asking for clarification of prostate cancer (PCA) grading in biopsy specimens with cancer present in <5% of the samples. It is correct that the worst grade should always be included, even if present in <5%. However, it is also common knowledge that the prognostic significance of such small foci of PCA is unreliable and that therapeutic recommendations based on such limited information should most probably be based on a second biopsy.
Active surveillance and watchful waiting are used in the EAU guidelines, reflecting different stages of PCA and different purposes of therapy. It becomes clear from the introductory sentence that the term ‘‘watchful waiting’’ is used to describe a treatment strategy that includes an active standpoint to postpone treatment until it is required. Active surveillance, however, has emerged as a true therapeutic alternative in men with PCA and a low risk of disease progression based on the high 20year PCA specific survival rates. We should have given a more precise definition when referring to further therapy: active surveillance is a clear therapeutic option for low-risk PCA, whereas watchful waiting is reserved for patients with advanced PCA when treatment is not delivered for curative intent. The data and the opinions given by the Cochrane review had been included in the EAU guidelines. With regard to the indication for prostate biopsy, we clearly have focused on the fact that there is no optimum prostate-specific antigen (PSA) threshold; therefore, the most reliable indicators such as PSA, percentage of free PCA, and PSA velocity have been included, in accordance with other published guidelines. We also have given the recommendation that values of 2.5–3.0 ng/ml should be used as a cut-off in younger men for performing a prostate biopsy. Basically, the indication for the detection of PCA needs a thorough discussion with the patient, independent of the PSA level. Local anesthesia was not considered to be a standard procedure in every single patient, although the results of most of the 23 published studies demonstrated some benefit with regard to biopsyassociated pain, since the results were not highly statistically significant and because there was a wide variation of the techniques used for periprostatic infiltration. Higher complication rates for interstitial brachytherapy have been reported consistently in most studies published to date. With regard to radical prostatectomy, however, a negative impact of
696
european urology 54 (2008) 692–700
previous transurethral resection of the prostate (TURP) has been shown for the laparoscopic approach only, whereas the open surgical approach might be surgically more challenging but there are no negative consequences on functional and oncologic outcomes. Active surveillance still is an option for very wellselected patients with clinically localized, smallvolume PCA and a limited life expectancy. The treatment decision is based primarily on the biopsy findings which—as we all know—are less predictable if not performed according to a well-defined standard. Reflecting the data of different retrospective analyses of guidelines compliance with regard to the performance and histopathologic analysis of prostate biopsies, we felt that a more stringent recommendation on the use of active surveillance would be best considering the high variability of the quality of prostate biopsies in Europe. We have extensively discussed the data of the prospective randomized trial ‘‘Radical prostatectomy versus watchful waiting’’ in the long version of the EAU guidelines, considering all the concerns raised by Dr. Kirollos. Extensive discussion of the pros and cons of nerve-sparing radical prostatectomy was not possible in the short version, owing simply to space limitations. However, there are no drawbacks of the nerve-sparing procedures: the functional outcome with regard to potency and continence is improved; the oncologic outcome is not harmed. The overall survival rates are given in the long version of the guidelines and the issue of radical prostatectomy in locally advanced disease is discussed extensively. The rationale for pelvic lymphadenectomy is not only cure but also adequate staging of the pelvic lymph nodes. Therefore, anatomic pelvic lymphadenectomy should always be performed in men with a higher likelihood of harbouring lymph node metastases in order to trigger individualized adjuvant therapeutic options. It was the aim of the short version of the guidelines to report the indications and the outcomes of the various treatment options for prostate cancer. Therefore, the different techniques of radiation oncology available nowadays have been described in the text. We have not included the newer variants such as intensity-modulated radiation therapy IMRT or high-dose radiation (HDR) brachytherapy, since the long-term data for the former are not available and there are no prospective randomized trials available demonstrating that HDR brachytherapy is superior to HDR therapy. This issue, however, is discussed in more detail in the long version of the manuscript.
With regard to cryosurgery, its potential role as salvage treatment is mentioned in Table 7. With regard to high-intensity focused ultrasound (HIFU), too few data with a too short follow-up are available to clearly define its role as an effective secondary treatment option with curative intent. The misprintings in section 11.3.3.3 in the long version have been corrected. The use of bisphosphonates has not been discussed in extensive detail with regard to the prevention of osteoporosis following androgendeprivation therapy for various reasons. There are small prospective clinical phase 2 trials available demonstrating a benefit of bisphosphonates to prevent osteoporosis. However, there are no clinical phase 3 trials, there is no Food and Drug Administration (FDA) approval with regard to the amino bisphosphonates, and there are no data available indicating that simple prophylactic measures such as sports, calcium, and vitamin D supplementation would be equivalent, as has been shown in patients with osteopenia. Again we would like to thank Dr. Kirollos for the valuable and constructive comments, which will help to further improve the next version of the guidelines.
Conflicts of interest Prof. Dr. Med. Axel Heidenreich has financial relationships as lecturer, consultant, and Advisory Board Member at Amgen, Ferring, Sanofi-Aventis, Novartis, Hoffmann-La Roche, Centocor, Astra Zeneca, and Ipsen Pharma. During the EAU meeting in Berlin, 2007, Prof. Gunnar Aus took part in a symposium related to high-intensity focused ultrasound (HIFU) for the treatment of prostate cancer. For chairing this symposium, he received financial compensation from EDAP, Lyon, France. There are no financial disclosures to be made for Prof. Bolla, Dr. Steven Joniau, Prof. V.B. Matveev, Prof. Hans Peter Schmid, or Prof. Filliberto Zattoni. References [1] Kirollos M. Re: Axel Heidenreich, Gunnar Aus, Michel Bolla et al. EAU guidelines on prostate cancer. Eur Urol 2008;53:68–80. [2] Heidenreich A, Aus G, Bolla M, Jonieau S, Matveev VB, Schmid HP, Zattoni F. EAU guidelines on prostate cancer. Eur Urol 2008;53:68–80. [3] http://www.uroweb.org/nc/professional-resources/guidelines/online/.
european urology 54 (2008) 692–700
Axel Heidenreich* University of Cologne, Cologne, Germany *Tel. +49 0221 478 87636; Fax: +49 0221 478 87901 E-mail address: [email protected]
697
April 9, 2008 Published online ahead of print on April 21, 2008 doi:10.1016/j.eururo.2008.04.034
DOIs of original articles: 10.1016/j.eururo.2007.09.002, 10.1016/j.eururo.2008.03.002
Re: Gunnar Wendt-Nordahl, Stephanie Huckele, Patrick Honeck, et al. 980-nm Diode Laser: A Novel Laser Technology for Vaporization of the Prostate. Eur Urol 2007;52:1723–8 We read with great interest the article by WendtNordahl et al [1] describing the ablation and coagulation properties of the diode laser device with an emission wavelength of 980 nm. However, the title of this article, ‘‘980-nm Diode Laser: A Novel Laser Technology for Vaporization of the Prostate,’’ is misleading. Although it suggests a novel treatment option for benign prostatic hyperplasia (BPH), the article merely describes studies with an ex vivo blood-perfused porcine kidney model. In this ex vivo model, a coagulation zone between 208.8 30.8 mm and 255 28.2 mm at a generator output power level of 100 W in the pulsed- and continuous-wave mode was observed. These results are similar to coagulation zones described for transurethral resection of the prostate (TURP) in the same manuscript. In a comparable experimental setting, our study group observed a mean coagulation zone of 10.2 1.07 mm for the 980 nm diode laser, indicating an approximately 50 deeper tissue penetration [2]. Only a limited number of original articles in current literature deal with in vivo diode laser treatment at 980 nm. In an in vivo porcine model, Ogan et al observed at 23 W (pulsed mode on-time 0.05 s; off-time 0.03 s) coagulation zones of 3 to 5 mm when performing laparoscopic partial nephrectomy [3]. Another in vivo study on mongrel dogs and diode laser treatment (l = 980 nm) of the gastric wall with 10 W (cw-mode) for 50 to 400 s showed thermal tissue damage between 8 mm (range: 5–11) and 11 mm (range: 8–15), respectively [4]. In conclusion, when one considers (1) laser physical principles, (2) our results in a comparable experimental setting, and (3) the current literature on this issue, the degree of coagulation zones of 208.8 30.8 mm to 255 28.2 mm at 100 W in the pulsed- and continuous-wave described by WendtNordahl et al, at a wavelength of 980 nm, seems rather questionable. The hypothesis that increased DOI of original article: 10.1016/j.eururo.2007.06.029
ablation properties and decreased coagulation depth of diode laser devices in comparison to potassium-titanyl-phosphate (KTP) laser systems may be explained by higher energy absorption of the epithelial surface has to be questioned, because both the optical penetration depth and the ex vivo and in vivo studies contradict this hypothesis. Conclusive verification of tissue ablation and coagulation zone is warranted for in vivo studies on prostate tissue before clinical evaluation of this laser system may be considered. Conflicts of interest: The authors have nothing to disclose.
References [1] Wendt-Nordahl G, Huckele S, Honeck P, et al. 980-nm diode laser: a novel laser technology for vaporization of the prostate. Eur Urol 2007;52:1723–8. [2] Seitz M, Ackermann A, Gratzke C, et al. Diode laser: ex vivo studies on vaporization and coagulation characteristics. Urologe A 2007;46:1242–7. [3] Ogan K, Wilhelm D, Lindberg G, et al. Laparoscopic partial nephrectomy with a diode laser: porcine results. J Endourol 2002;16:749–53. [4] Maema A, Hashimoto D, Yokoya S, Shoji M, Makuuchi M. Spatially selective laser coagulation of the gastric wall: a new methodology. J Surg Res 2002;103:114–20. Michael Seitz* Department of Urology, University Hospital Grosshadern, Ludwig Maximilians University, Munich, Germany Ronald Sroka Laser Laboratory, University Hospital Grosshadern, Ludwig Maximilians University, Munich, Germany *Corresponding author. Urologische Klinik und Poliklinik, Klinikum der Universita¨t, Campus Grosshadern, Ludwig Maximilians Universita¨t, Mu¨nchen, Deutschland. Tel. +49 (0) 89 7095 7741; Fax: +49 (0) 89 7095 4746 E-mail address: [email protected] (M. Seitz) March 6, 2008 Published online ahead of print on March 14, 2008 doi:10.1016/j.eururo.2008.03.005