- Email: [email protected]
Re: D2 Lymphadenectomy Alone or with Para-aortic Nodal Dissection for Gastric Cancer
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EUROPEAN UROLOGY 56 (2009) 740–746
several reasons. It adds to our understanding of the molecular basis of prostate cancer progression and indicates that the so-called hormone-refractory state is not absolute. Treatment resulted in a significant decrease of PSA in two-thirds of patients and partial regression of distant metastases in more than one-third. In fact, abiraterone acetate might be more effective than taxane-based chemotherapy in CRPC on the one hand and might be less toxic on the other hand. Side effects were tolerable, and the frequently occurring mineralocorticoid excess was well managed by the antagonist eplerenone. Ongoing and planned randomized phase 3 trials with the primary end point of overall survival will eventually define the role of abiraterone acetate in endocrine therapy of prostate cancer.
[2] Klotz L, Boccon-Gibod L, Shore ND, et al. The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer. BJU Int 2008;102:1531–8. [3] Barrie SE, Potter GA, Goddard PM, et al. Pharmacology of novel steroidal inhibitors of cytochrome P450(17) alpha (17 alpha-hydroxylase/C17-20 lyase). J Steroid Biochem Mol Biol 1994;50:267–73. [4] Eichenberger T, Trachtenberg J. Effects of high-dose ketoconazole on patients who have androgen-independent prostatic cancer. Can J Surg 1989;32:349–52. [5] Attard G, Reid AH, Yap TA, et al. Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castrationresistant prostate cancer commonly remains hormone driven. J Clin Oncol 2008;26:4563–71. Hans-Peter Schmid*, Daniel S. Engeler Department of Urology, Kantonsspital, St. Gallen, Switzerland
Conflicts of interest: The authors have nothing to disclose. *Corresponding author. Kantonsspital, Urology, St-Gallen, 9007, Switzerland.
References
E-mail address: [email protected] (H.-P. Schmidt)
[1] Heidenreich A, Aus G, Bolla M, et al. EAU guidelines on prostate cancer. Eur Urol 2008;53:68–80.
Re: D2 Lymphadenectomy Alone or with Para-aortic Nodal Dissection for Gastric Cancer Sasako M, Sano T, Yamamoto S, et al; Japan Clinical Oncology Group N Engl J Med 2008;359:453–62 Experts’ summary: Gastrectomy with an extended regional (D2) lymphadenectomy is the standard treatment for curable gastric cancer in Asia; however, because of a 10–30% rate of para-aortic node involvement, additional para-aortic nodal dissection (PAND) has been performed in Japan since the 1980 s for patients with advanced stage disease. This landmark study asked if the addition of PAND to the D2 lymphadenectomy improved survival for patients with stage T2-4 tumors. The overall incidence of surgery-related complications was 20.9% in the D2 lymphadenectomy group and 28.1% in the group assigned to D2 lymphadenectomy plus PAND ( p = 0.07). The authors observed no significant differences in recurrence-free or overall survival rates between the two groups. Experts’ comments: The experience with defining the appropriate extent of gastric nodal dissection may provide insight into the challenges urologists face when determining the appropriate extent of nodal dissection for patients undergoing radical cystectomy. PAND was routinely practiced and accepted largely based on the notion of positive nodes in the extended field and observational data that supported a benefit of this approach. The aforementioned randomized trial, however, revealed no survival benefit and an increased frequency of surgical-related complications with significance of p = 0.07.
DOI: 10.1016/j.eururo.2009.07.012
In patients undergoing radical cystectomy for bladder cancer, limited and extended pelvic lymph node dissections (PLNDs) lack universally accepted definitions. The cranial extent of an extended PLND may include dissections up to the mid common iliac, the aortic bifurcation, or the inferior mesenteric artery. Support for an extended PLND stems from the incidence of nodal metastasis outside the standard template and from observational studies, which seem to provide a clinically meaningful therapeutic benefit compared with a limited approach [1]. But the validity of the influence of extended PLNDs on survival awaits data from prospective trials such as that being conducted by the Association of Urogenital Oncology of the German Cancer Association, which aims to compare conventional versus extended PLND in patients undergoing radical cystectomy. Differences in outcomes between patients undergoing limited or standard PLND versus extended PLND are particularly difficult to interpret from observational data. The association between the extent of the dissection and the outcome of interests is modified by the presence or absence of node involvement. In other words, we anticipate that the majority of patients that would benefit from an extended dissection are those with node-positive disease, whereas patients with node-negative disease are less likely to obtain benefit from an extended dissection. Because node staging is directly influenced by the extent of the dissection, patients found to have node-positive disease with a standard dissection must have a higher nodal disease burden compared with those patients found to have nodepositive disease with an extended dissection. The magnitude of this bias is not known, but its direction would render results that systematically favor an approach that yields higher lymph nodes.
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EUROPEAN UROLOGY 56 (2009) 740–746
As with gastric cancer, the results of studies addressing the extent of lymphadenectomy in patients with bladder cancer may be subject to biases based on surgeon and center differences. To avoid these potential pitfalls, quality measures ensuring standardization of the extent of dissection, such as regional node quantification and/or intraoperative photography, should be considered in future studies addressing extent of lymphadenectomy during radical cystectomy for bladder cancer. One limitation of the study by Sasako et al was that the incidence of nodal metastasis (8.5%) was lower than expected based on observational data (10–30%). The incidence of nodal metastasis in the extended PLND template will be an important determinant of the potential benefit of an extended dissection. Finally, defining the appropriate extent of PLND in bladder cancer is especially important due to the increased use of robotic-assisted radical cystectomy (RARC). Although the da Vinci S system appears to offer improved access, extended PLNDs are demanding with RARC because of the difficulty with cranial and internal iliac node dissections [2,3].
Conflicts of interest: The authors have nothing to disclose.
References [1] Karl A, Carroll PR, Gschwend JE, et al. The impact of lymphadenectomy and lymph node metastasis on the outcomes of radical cystectomy for bladder cancer. Eur Urol 2009;55:826–35. [2] Herr HW. Editorial comment on: robotic-assisted laparoscopic radical cystectomy with extracorporeal urinary diversion: initial experience. Eur Urol 2008;54:579. [3] Murphy DG, Challacombe BJ, Elhage O, et al. Robotic-assisted laparoscopic radical cystectomy with extracorporeal urinary diversion: initial experience. Eur Urol 2008;54:570–80. Robert S. Svatek, Colin P.N. Dinney* MD Anderson Cancer Center, Urologic Oncology, Houston, TX, USA *Corresponding author. University of Texas, M.D. Anderson Cancer Center - Urology, Houston, TX 77030 USA. E-mail address: [email protected] (C.P.N. Dinney) DOI: 10.1016/j.eururo.2009.07.013
EUROPEAN UROLOGY 56 (2009) 740–746
several reasons. It adds to our understanding of the molecular basis of prostate cancer progression and indicates that the so-called hormone-refractory state is not absolute. Treatment resulted in a significant decrease of PSA in two-thirds of patients and partial regression of distant metastases in more than one-third. In fact, abiraterone acetate might be more effective than taxane-based chemotherapy in CRPC on the one hand and might be less toxic on the other hand. Side effects were tolerable, and the frequently occurring mineralocorticoid excess was well managed by the antagonist eplerenone. Ongoing and planned randomized phase 3 trials with the primary end point of overall survival will eventually define the role of abiraterone acetate in endocrine therapy of prostate cancer.
[2] Klotz L, Boccon-Gibod L, Shore ND, et al. The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer. BJU Int 2008;102:1531–8. [3] Barrie SE, Potter GA, Goddard PM, et al. Pharmacology of novel steroidal inhibitors of cytochrome P450(17) alpha (17 alpha-hydroxylase/C17-20 lyase). J Steroid Biochem Mol Biol 1994;50:267–73. [4] Eichenberger T, Trachtenberg J. Effects of high-dose ketoconazole on patients who have androgen-independent prostatic cancer. Can J Surg 1989;32:349–52. [5] Attard G, Reid AH, Yap TA, et al. Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castrationresistant prostate cancer commonly remains hormone driven. J Clin Oncol 2008;26:4563–71. Hans-Peter Schmid*, Daniel S. Engeler Department of Urology, Kantonsspital, St. Gallen, Switzerland
Conflicts of interest: The authors have nothing to disclose. *Corresponding author. Kantonsspital, Urology, St-Gallen, 9007, Switzerland.
References
E-mail address: [email protected] (H.-P. Schmidt)
[1] Heidenreich A, Aus G, Bolla M, et al. EAU guidelines on prostate cancer. Eur Urol 2008;53:68–80.
Re: D2 Lymphadenectomy Alone or with Para-aortic Nodal Dissection for Gastric Cancer Sasako M, Sano T, Yamamoto S, et al; Japan Clinical Oncology Group N Engl J Med 2008;359:453–62 Experts’ summary: Gastrectomy with an extended regional (D2) lymphadenectomy is the standard treatment for curable gastric cancer in Asia; however, because of a 10–30% rate of para-aortic node involvement, additional para-aortic nodal dissection (PAND) has been performed in Japan since the 1980 s for patients with advanced stage disease. This landmark study asked if the addition of PAND to the D2 lymphadenectomy improved survival for patients with stage T2-4 tumors. The overall incidence of surgery-related complications was 20.9% in the D2 lymphadenectomy group and 28.1% in the group assigned to D2 lymphadenectomy plus PAND ( p = 0.07). The authors observed no significant differences in recurrence-free or overall survival rates between the two groups. Experts’ comments: The experience with defining the appropriate extent of gastric nodal dissection may provide insight into the challenges urologists face when determining the appropriate extent of nodal dissection for patients undergoing radical cystectomy. PAND was routinely practiced and accepted largely based on the notion of positive nodes in the extended field and observational data that supported a benefit of this approach. The aforementioned randomized trial, however, revealed no survival benefit and an increased frequency of surgical-related complications with significance of p = 0.07.
DOI: 10.1016/j.eururo.2009.07.012
In patients undergoing radical cystectomy for bladder cancer, limited and extended pelvic lymph node dissections (PLNDs) lack universally accepted definitions. The cranial extent of an extended PLND may include dissections up to the mid common iliac, the aortic bifurcation, or the inferior mesenteric artery. Support for an extended PLND stems from the incidence of nodal metastasis outside the standard template and from observational studies, which seem to provide a clinically meaningful therapeutic benefit compared with a limited approach [1]. But the validity of the influence of extended PLNDs on survival awaits data from prospective trials such as that being conducted by the Association of Urogenital Oncology of the German Cancer Association, which aims to compare conventional versus extended PLND in patients undergoing radical cystectomy. Differences in outcomes between patients undergoing limited or standard PLND versus extended PLND are particularly difficult to interpret from observational data. The association between the extent of the dissection and the outcome of interests is modified by the presence or absence of node involvement. In other words, we anticipate that the majority of patients that would benefit from an extended dissection are those with node-positive disease, whereas patients with node-negative disease are less likely to obtain benefit from an extended dissection. Because node staging is directly influenced by the extent of the dissection, patients found to have node-positive disease with a standard dissection must have a higher nodal disease burden compared with those patients found to have nodepositive disease with an extended dissection. The magnitude of this bias is not known, but its direction would render results that systematically favor an approach that yields higher lymph nodes.
746
EUROPEAN UROLOGY 56 (2009) 740–746
As with gastric cancer, the results of studies addressing the extent of lymphadenectomy in patients with bladder cancer may be subject to biases based on surgeon and center differences. To avoid these potential pitfalls, quality measures ensuring standardization of the extent of dissection, such as regional node quantification and/or intraoperative photography, should be considered in future studies addressing extent of lymphadenectomy during radical cystectomy for bladder cancer. One limitation of the study by Sasako et al was that the incidence of nodal metastasis (8.5%) was lower than expected based on observational data (10–30%). The incidence of nodal metastasis in the extended PLND template will be an important determinant of the potential benefit of an extended dissection. Finally, defining the appropriate extent of PLND in bladder cancer is especially important due to the increased use of robotic-assisted radical cystectomy (RARC). Although the da Vinci S system appears to offer improved access, extended PLNDs are demanding with RARC because of the difficulty with cranial and internal iliac node dissections [2,3].
Conflicts of interest: The authors have nothing to disclose.
References [1] Karl A, Carroll PR, Gschwend JE, et al. The impact of lymphadenectomy and lymph node metastasis on the outcomes of radical cystectomy for bladder cancer. Eur Urol 2009;55:826–35. [2] Herr HW. Editorial comment on: robotic-assisted laparoscopic radical cystectomy with extracorporeal urinary diversion: initial experience. Eur Urol 2008;54:579. [3] Murphy DG, Challacombe BJ, Elhage O, et al. Robotic-assisted laparoscopic radical cystectomy with extracorporeal urinary diversion: initial experience. Eur Urol 2008;54:570–80. Robert S. Svatek, Colin P.N. Dinney* MD Anderson Cancer Center, Urologic Oncology, Houston, TX, USA *Corresponding author. University of Texas, M.D. Anderson Cancer Center - Urology, Houston, TX 77030 USA. E-mail address: [email protected] (C.P.N. Dinney) DOI: 10.1016/j.eururo.2009.07.013