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Extent of Pelvic Lymph Node Dissection During Radical Cystectomy: Where and Why!
EUROPEAN UROLOGY 57 (2010) 212–213
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Platinum Priority – Editorial Referring to the article published on pp. 205–211 of this issue
Extent of Pelvic Lymph Node Dissection During Radical Cystectomy: Where and Why! Harry W. Herr Department of Urology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021-6007, USA
In their classic article on radical cystectomy published in 1962 [1], Whitmore and Marshall described the standard template for a bilateral pelvic lymph node dissection (PLND). PLND is begun along the lateral margin of the common iliac artery, where the ureter crosses the vessel, and continues distally to Cooper’s ligament, removing all areolar tissue, fat, and nodes lateral, above, and below the common and external iliac artery and vein. The obturator nodes are removed from the pelvic sidewall and obturator fossa, completely resecting the obturator artery and vein at their origin from the hypogastric artery to flush with the obturator foramen. The posterior pelvic wall is neatly dissected of nodal tissue, exposing the internal iliac vessels and their ramifications, and extended up to remove the presacral nodes. It is important to remove all nodes medial and lateral to the hypogastric vessels, including underneath the common iliac vessels at their bifurcation. When nodes are left behind, this location is a common site of pelvic recurrence. The deep dissection exposes the fascia over the sciatic nerve and removes fat and adjacent lymphatics from the ischiorectal fossa, visual landmarks confirming a complete hypogastric dissection. A standard PLND has the following limits: proximal, midportion of the common iliac artery; lateral, genitofemoral nerve; medial, bladder wall; distal, inguinal ligament; and inferior, pelvic floor and hypogastric vessels, lying on the deep muscular and bony walls of the pelvis. This is considered the standard PLND performed during radical cystectomy. Anything less is a limited dissection; anything more (up to bifurcation of aorta and above) can be called an extended PLND. The rationale for PLND during cystectomy is improved staging and even cure in a select minority of patients with
positive nodes. Collective experience from a substantial number of single-surgeon, institutional, multicenter, cohort, comparative, and population-based studies show that PLND affects outcome after radical cystectomy [2]. The most persuasive data, however, comes from a secondary analysis of a randomized, cooperative group trial involving many centers and individual surgeons [3]. Twice as many patients survived longer (whether or not they received neoadjuvant chemotherapy) if they had a standard PLND than those who had no or limited PLND, and standard PLND conferred a survival advantage in both node-positive and node-negative patients. The anatomic boundaries of PLND are still hotly debated, largely because urologists have confused the definitions of node templates and have resorted to node counts as a proxy measure defining an adequate PLND. Neither is justified. The standard PLND, as originally described, includes the nodes at least along the distal half of the common iliac vessels together with its bifurcation (not just external iliac and obturator nodes, as the standard PLND is commonly understood today; including common iliac nodes does not define an extended PLND). The number of positive nodes located above the ureters crossing the common iliac vessels varies between 4% and 8%, and no one has shown convincingly that removing nodes from the proximal common iliac artery and higher cures patients [4]. Likewise, counting numbers of nodes to define a ‘‘complete’’ PLND has its own inherent limitations, not the least of which is that node counts do not reflect whether the critical nodes were removed, and some patients have fewer nodes than others. In our institution, for example, where we routinely perform cystectomy in all but the most morbidly ill, the same standard PLND yields from 6 to 52 nodes in different patients [5]. One study implied that there
DOI of original article: 10.1016/j.eururo.2009.10.026 E-mail address: [email protected]. 0302-2838/$ – see back matter # 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.eururo.2009.10.028
EUROPEAN UROLOGY 57 (2010) 212–213
was no maximal limit to number of nodes that should be removed [6], whereas the cooperative group study showed that removing >15 nodes conferred no better survival than dissecting just 10 nodes [3]. How can urologists make sense out of such disparate information? An ongoing German study comparing standard versus extended PLND might resolve the issue but not if currently defined and confusing PLND templates are compared. Furthermore, a recent metaanalysis in rectal cancer showed no benefit in terms of survival or local control to extended lymphadenectomy [7]. In a provocative paper in this issue of European Urology, the outstanding team at Bern headed by Urs Studer has added science to the debate [8]. Using a radioactive tracer in 60 patients, they intraoperatively mapped the distribution of nodes regional to the bladder while performing a PLND from ureteroiliac junction into the small pelvis, representing the first study documenting primary lymphatic landing sites of the bladder. The results have significant implications for clinical practice. First, the number of lymph nodes varies among patients, making it difficult to judge the quality of PLND by node counts. Most important is the PLND template. Second, nodes are widely distributed in the pelvis (mandating bilateral PLND); however, only 8% were cephalad to the ureteroiliac junction (and all patients had simultaneous radioactive nodes inferiorly). The authors ask whether it is worth dissecting above this level and persuasively argue no, since node distribution patterns indicate that a more extended dissection would entail unnecessary risks that may benefit only a rare patient. Third, a meticulous dissection of nodes medial to the internal iliac vessels is necessary because almost half (42%) of the 26% of nodes in this region were located medial to the hypogastric artery. A major drawback of the study is that patients who had prior pelvic radiotherapy, neoadjuvant chemotherapy, history of pelvic surgery, or coincident prostate cancer were excluded.
213
Unfortunately, such patients represent the majority of patients I operate on and, likely, are challenging most urologic oncologists today. Such limitations notwithstanding, the Bern group has brought us back to reality before we became inexplicitly and arbitrarily diverted to redefine the limits of PLND and emphasize node counts as the holy grail for quality of a proper PLND. Why can’t we simply perform PLND in each patient well, following the original template faithfully? That is exactly what this paper tells us to do! Conflicts of interest: The author has nothing to disclose.
References [1] Whitmore Jr WF, Marshall VF. Radical cystectomy for cancer of the bladder. J Urol 1962;87:853–68. [2] 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. [3] Herr HW, Faulkner JR, Grossman HB, et al. Surgical factors influence bladder cancer outcomes: a cooperative group report. J Clin Oncol 2004;22:2781–9. [4] Vazina A, Dugi D, Shariat SF, et al. Stage specific lymph node metastasis mapping in radical cystectomy specimens. J Urol 2004;171:1830–4. [5] Herr HW, Lee C, Chang S, et al. Standardization of radical cystectomy and pelvic node dissection for bladder cancer: a collaborative group report. J Urol 2004;171:1823–8. [6] Koppie TM, Vickers AJ, Bochner BH. Standardization of pelvic lymphadenectomy performed at radical cystectomy. Cancer 2006; 107:2368–74. [7] Georgiou P, Tan E, Gouvas N, et al. Extended lymphadenectomy versus conventional surgery for rectal cancer: a meta-analysis. Lancet Oncol 2009;10:1053–62. [8] Roth B, Wissmeyer MP, Zehnder P, et al. A new multimodality technique accurately maps the primary lymphatic landing sites of the bladder. Eur Urol 2010;57:205–11.
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Platinum Priority – Editorial Referring to the article published on pp. 205–211 of this issue
Extent of Pelvic Lymph Node Dissection During Radical Cystectomy: Where and Why! Harry W. Herr Department of Urology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021-6007, USA
In their classic article on radical cystectomy published in 1962 [1], Whitmore and Marshall described the standard template for a bilateral pelvic lymph node dissection (PLND). PLND is begun along the lateral margin of the common iliac artery, where the ureter crosses the vessel, and continues distally to Cooper’s ligament, removing all areolar tissue, fat, and nodes lateral, above, and below the common and external iliac artery and vein. The obturator nodes are removed from the pelvic sidewall and obturator fossa, completely resecting the obturator artery and vein at their origin from the hypogastric artery to flush with the obturator foramen. The posterior pelvic wall is neatly dissected of nodal tissue, exposing the internal iliac vessels and their ramifications, and extended up to remove the presacral nodes. It is important to remove all nodes medial and lateral to the hypogastric vessels, including underneath the common iliac vessels at their bifurcation. When nodes are left behind, this location is a common site of pelvic recurrence. The deep dissection exposes the fascia over the sciatic nerve and removes fat and adjacent lymphatics from the ischiorectal fossa, visual landmarks confirming a complete hypogastric dissection. A standard PLND has the following limits: proximal, midportion of the common iliac artery; lateral, genitofemoral nerve; medial, bladder wall; distal, inguinal ligament; and inferior, pelvic floor and hypogastric vessels, lying on the deep muscular and bony walls of the pelvis. This is considered the standard PLND performed during radical cystectomy. Anything less is a limited dissection; anything more (up to bifurcation of aorta and above) can be called an extended PLND. The rationale for PLND during cystectomy is improved staging and even cure in a select minority of patients with
positive nodes. Collective experience from a substantial number of single-surgeon, institutional, multicenter, cohort, comparative, and population-based studies show that PLND affects outcome after radical cystectomy [2]. The most persuasive data, however, comes from a secondary analysis of a randomized, cooperative group trial involving many centers and individual surgeons [3]. Twice as many patients survived longer (whether or not they received neoadjuvant chemotherapy) if they had a standard PLND than those who had no or limited PLND, and standard PLND conferred a survival advantage in both node-positive and node-negative patients. The anatomic boundaries of PLND are still hotly debated, largely because urologists have confused the definitions of node templates and have resorted to node counts as a proxy measure defining an adequate PLND. Neither is justified. The standard PLND, as originally described, includes the nodes at least along the distal half of the common iliac vessels together with its bifurcation (not just external iliac and obturator nodes, as the standard PLND is commonly understood today; including common iliac nodes does not define an extended PLND). The number of positive nodes located above the ureters crossing the common iliac vessels varies between 4% and 8%, and no one has shown convincingly that removing nodes from the proximal common iliac artery and higher cures patients [4]. Likewise, counting numbers of nodes to define a ‘‘complete’’ PLND has its own inherent limitations, not the least of which is that node counts do not reflect whether the critical nodes were removed, and some patients have fewer nodes than others. In our institution, for example, where we routinely perform cystectomy in all but the most morbidly ill, the same standard PLND yields from 6 to 52 nodes in different patients [5]. One study implied that there
DOI of original article: 10.1016/j.eururo.2009.10.026 E-mail address: [email protected]. 0302-2838/$ – see back matter # 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.eururo.2009.10.028
EUROPEAN UROLOGY 57 (2010) 212–213
was no maximal limit to number of nodes that should be removed [6], whereas the cooperative group study showed that removing >15 nodes conferred no better survival than dissecting just 10 nodes [3]. How can urologists make sense out of such disparate information? An ongoing German study comparing standard versus extended PLND might resolve the issue but not if currently defined and confusing PLND templates are compared. Furthermore, a recent metaanalysis in rectal cancer showed no benefit in terms of survival or local control to extended lymphadenectomy [7]. In a provocative paper in this issue of European Urology, the outstanding team at Bern headed by Urs Studer has added science to the debate [8]. Using a radioactive tracer in 60 patients, they intraoperatively mapped the distribution of nodes regional to the bladder while performing a PLND from ureteroiliac junction into the small pelvis, representing the first study documenting primary lymphatic landing sites of the bladder. The results have significant implications for clinical practice. First, the number of lymph nodes varies among patients, making it difficult to judge the quality of PLND by node counts. Most important is the PLND template. Second, nodes are widely distributed in the pelvis (mandating bilateral PLND); however, only 8% were cephalad to the ureteroiliac junction (and all patients had simultaneous radioactive nodes inferiorly). The authors ask whether it is worth dissecting above this level and persuasively argue no, since node distribution patterns indicate that a more extended dissection would entail unnecessary risks that may benefit only a rare patient. Third, a meticulous dissection of nodes medial to the internal iliac vessels is necessary because almost half (42%) of the 26% of nodes in this region were located medial to the hypogastric artery. A major drawback of the study is that patients who had prior pelvic radiotherapy, neoadjuvant chemotherapy, history of pelvic surgery, or coincident prostate cancer were excluded.
213
Unfortunately, such patients represent the majority of patients I operate on and, likely, are challenging most urologic oncologists today. Such limitations notwithstanding, the Bern group has brought us back to reality before we became inexplicitly and arbitrarily diverted to redefine the limits of PLND and emphasize node counts as the holy grail for quality of a proper PLND. Why can’t we simply perform PLND in each patient well, following the original template faithfully? That is exactly what this paper tells us to do! Conflicts of interest: The author has nothing to disclose.
References [1] Whitmore Jr WF, Marshall VF. Radical cystectomy for cancer of the bladder. J Urol 1962;87:853–68. [2] 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. [3] Herr HW, Faulkner JR, Grossman HB, et al. Surgical factors influence bladder cancer outcomes: a cooperative group report. J Clin Oncol 2004;22:2781–9. [4] Vazina A, Dugi D, Shariat SF, et al. Stage specific lymph node metastasis mapping in radical cystectomy specimens. J Urol 2004;171:1830–4. [5] Herr HW, Lee C, Chang S, et al. Standardization of radical cystectomy and pelvic node dissection for bladder cancer: a collaborative group report. J Urol 2004;171:1823–8. [6] Koppie TM, Vickers AJ, Bochner BH. Standardization of pelvic lymphadenectomy performed at radical cystectomy. Cancer 2006; 107:2368–74. [7] Georgiou P, Tan E, Gouvas N, et al. Extended lymphadenectomy versus conventional surgery for rectal cancer: a meta-analysis. Lancet Oncol 2009;10:1053–62. [8] Roth B, Wissmeyer MP, Zehnder P, et al. A new multimodality technique accurately maps the primary lymphatic landing sites of the bladder. Eur Urol 2010;57:205–11.