Laparoscopic Extended Pelvic Lymph Node Dissection for Prostate Cancer: Description of the Surgical Technique and Initial Results

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1 european urology 52 (2007) available at journal homepage: Surgery in Motion Laparoscopic Extended Pelvic Lymph Node Dissection for Prostate Cancer: Description of the Surgical Technique and Initial Results Jean-Baptiste Lattouf a, *, Avi Beri a, Stephan Jeschke a, Wolfgang Sega b, Karl Leeb a, Günter Janetschek a a Department of Urology, Krankenhaus der Elisabethinen, Linz, Austria b Department of Pathology, Krankenhaus der Barmherzigen Schwestern, Linz, Austria Article info Article history: Accepted April 24, 2007 Published online ahead of print on May 2, 2007 Keywords: Laparoscopy Lymph node excision Neoplasm staging Prostatectomy Prostatic neoplasms Abstract Objective: In patients with prostate cancer, extended pelvic lymph node dissection (eplnd) yields a higher number of lymph node metastases (LNM) than standard pelvic lymph node dissection (PLND) of the obturator fossa only. We describe our laparoscopic technique of extended lymph node dissection and provide the number and locations of positive lymph nodes from our experience. Methods: In a total of 35 selected patients with clinically localized prostate cancer, laparoscopic eplnd was performed prior to laparoscopic radical prostatectomy. The template included the genitofemoral nerve up to the bifurcation of the common iliac artery and down to the epigastric artery. In the split and roll technique the internal and external iliac arteries including the bifurcation and the external iliac vein were completely mobilized. After freeing the obturator nerve, the entire lymph node package was released from the pelvic side wall. Results: Mean operative time was 90 min/patient. The complications were two temporary and reversible neurapraxias (ischiatic nerve and obturator nerve), one deep vein thrombosis, and two lymphoceles. One lymphocele healed conservatively; the second was marsupialized laparoscopically. Eleven (31.4%) patients had lymph node metastases; their mean prostate-specific antigen (PSA) level was ng/ml (range: ng/ml) and their median Gleason sum in biopsy was 7 (range: 6 8). Mean size of the LNM was mm (range: 0.2 8). In 5 of the 11 patients with LNM these were detected exclusively outside the obturator fossa. LNM were in the obturator fossa only in two (one bilateral), around the external iliac artery only in two, around the internal iliac artery only in two, and around the external iliac artery and internal iliac only in one patient. Conclusions: Laparoscopic eplnd can be combined with laparoscopic radical prostatectomy. Standardization of the technique facilitates surgery to a great extent. e-plnd detects LNM in a significant number of patients. The majority of LNM are outside the obturator fossa. The transperitoneal approach allows a wide exposure and is the most important factor to enable successful eplnd. # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. KH Elisabethinen Linz, Fadingerstrasse 1, A-4010 Linz, Austria. Tel ; Fax: address: jean-baptiste.lattouf@umontreal.ca (J.-B. Lattouf) /$ see back matter # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi: /j.eururo

2 1348 european urology 52 (2007) Introduction Table 1 Patient demographics Since the advent of the prostate-specific antigen (PSA) era, the finding of lymph node metastasis in operative candidates with prostate cancer has decreased significantly [1 6]. However, most of the reported data pertains to a dissection template limited to the obturator fossa. This template is somewhat in disregard of earlier studies on the lymph drainage of the prostate, which specifically show that drainage is mainly to the internal iliac nodes [7]. Using extended pelvic lymph node dissection (eplnd), the incidence of lymph node metastases (LNM) has been recently reported to be higher than that in the limited dissection. In fact, more than half of metastases to lymph nodes are found outside the standard template of dissection [8 10]. Compounding this finding are reports of a possible survival benefit in patients with minimal LNM dating as far back as 1982, although this remains the subject of intense controversy [11 15]. Laparoscopic PLND has already been described for the limited template PLND [16 18], but to our knowledge, technical description of extended laparoscopic PLND has been rarely reported and no standardized approach is commonly adopted. We herein report our preliminary experience with laparoscopic eplnd with up to 2 yr of follow-up in a selected cohort of patients, and propose a detailed, step-by-step surgical approach to this procedure. No. of patients 35 Mean age, yr (median, range) 63 (63, 48 76) Mean preoperative PSA, ng/ml 16.5 (11.7, ) (median, range) Gleason score, no. (%) 4 2 (5.7%) 5 3 (8.6 %) 6 13 (37.1%) 7 11 (31.4%) 8 5 (14.3%) 9 1 (2.9) Stage ct1 23 (65.7%) ct2 11 (31.4%) ct3 1 (2.9%) PSA = prostate-specific antigen Description of the technique All interventions were performed by a single surgeon (G.J.) using a transperitoneal approach in all but one case (2.8%), which was done at the beginning of our experience and for which a preperitoneal approach was used (the Discussion provides further details). We used five ports for both approaches: a 10-mm port for the camera through a periumbilical incision, a 11/12-mm port midway between the umbilicus and pubic symphysis, two 5-mm ports at the right and left iliac fossa midway between umbilicus and anterior superior iliac spine, and the last 5-mm port on the right side superolateral to the previous port. 2. Patients and methods 2.1. Patient population All patients in our center undergoing radical prostatectomy are enrolled in an ongoing prospective, sentinel lymph node study of which initial results have already been published [19]. Extended unilateral or bilateral PLND is performed on these patients for two indications, respectively: (1) no sentinel lymph node is detected on the ipsilateral pelvic sidewall intraoperatively or (2) the frozen section of the sentinel lymph node is positive for metastatic prostate cancer. Thus, every patient receives systematically bilateral PLND (either sentinel or extended). Between April 2004 and November 2005, a total of 174 patients underwent radical prostatectomy in our center, of whom 69 satisfied the criteria for inclusion in the sentinel lymph node study (PSA 5 ng/ml or Gleason score 6). Of this last subset, 35 men had an indication for an eplnd and were included in this study. Mean age was 63 yr (median: 63 yr; range: yr) and mean preoperative PSA was 16.5 ng/ml (median: 11.7 ng/ml; range: ng/ml). Table 1 presents the patient demographics. None of the patients had received preoperative hormonal therapy. Fig. 1 Dissection template of extended pelvic lymph node dissection in prostate cancer. (A) External iliac packet; (B) obturator packet; (C) internal iliac packet. 1, aorta; 2, common iliac artery; 3, external iliac artery; 4, internal iliac artery; 5, external iliac vein; 6, obturator vessels; 7, obturator nerve; 8, obliterated umbilical artery; 9, epigastric vessels; 10, psoas muscle; 11, genitofemoral nerve.

3 european urology 52 (2007) Fig. 2 (A) Anatomic landmarks of the dissection from an endoscopic view. (B) 1, vas deferens; 2, ureter; 3, common iliac artery; 4, obliterated medial umbilical ligament; 5, Douglas pouch. The template of the lymph node dissection included the genitofemoral nerve anterolaterally, the internal iliac artery posteromedially, the bifurcation of the common iliac artery cranially, and the origin of the epigastric vessels caudally. The dissection was limited laterally by the pelvic wall musculature. Fig. 1 illustrates the template and Fig. 2 shows the main anatomic landmarks form and endoscopic view. The specific steps of the dissection were as follows: (1) Incision of the peritoneum laterally to the medial umbilical ligament and parallel to the external iliac artery (Fig. 3). (2) Identification and transection of the vas as it is encountered (Fig. 4). (3) Development of the preperitoneal fat plane down to the superior pubic ramus (Fig. 5). (4) Tracing the medial umbilical ligament down to its junction with the internal iliac artery (Fig. 6) and identifying the ureter at its crossing with the superior vesical artery. (5) Identification of the bifurcation of the common iliac artery and the external iliac artery, as well as the external and internal iliac veins. (6) Identifying the genitofemoral nerve and isolating it along its course from the bifurcation of the common iliac artery to the origin of the epigastric vessels. (7) Splitting the fibrofatty tissue overlying the internal iliac artery and vein followed by the same maneuver for the external iliac artery and vein (Figs. 7 and 8). (8) After freeing the obturator nerve (Fig. 9), separating the aforementioned fibrofatty tissue from the lateral pelvic wall. (9) Ligating the remaining attached portions of the lymph node packets thus obtained using laparoscopic Endo-clips and removing the packets en bloc. Specimens were sent separately for the external iliac, obturator fossa, and internal iliac regions. In some cases where intracorporeal separation of the packet was not possible for the obturator fossa and internal iliac regions, packets from these regions were sent as one specimen to pathology. All patients underwent laparoscopic radical prostatectomy after their lymph node dissection. Biochemical recurrence on follow-up was defined as PSA 0.4 ng/ml [20 22] Pathologic examination Only one experienced pathologist (W.S.) performed the tissue examination. As mentioned, we make a point of sending Fig. 3 Incision of the peritoneum overlying the common iliac artery*.

4 1350 european urology 52 (2007) Fig. 4 (A) Transection of the vas deferens. (B) 1, obliterated medial umbilical ligament; 2, vas deferens. Fig. 5 (A) Dissection of the avascular plane lateral to the umbilical ligament down to the pubic bone. (B) 1, pubic bone; 2, obturator nerve; 3, pelvic wall musculature; 4, peritoneal incision (deflected). separate lymph node packages to maximize lymph node inspection. Specimens were dissected by the pathologist and examined macroscopically to identify all lymph nodes. Every specimen looking like a lymph node was then sectioned and examined. Microscopic postoperative histopathologic examination of the sentinel and nonsentinel lymph nodes included a standard protocol of step sections in 250-mm sequences (conventional hematoxylin and eosin staining) and Fig. 6 (A) Dissection of the umbilical ligament down to its origin on the internal iliac artery. (B) 1, internal iliac artery; 2, medial umbilical ligament; 3, peritoneal fold.

5 european urology 52 (2007) Fig. 7 (A) Splitting over the internal iliac vessels. (B) 1, internal iliac artery; 2, internal iliac vein. immunohistochemistry (pan-cytokeratin) of each third step, respectively. The histopathologic results for each lymph node were catalogued Statistical methods Only descriptive statistics are provided given the limited sample being studied. 3. Results A total of 47 pelvic sidewalls in 35 patients with eplnds were analyzed (unilateral, 23; bilateral, 12). Mean operative time for the lymph node dissection was 90 min/patient. Mean number of lymph nodes retrieved was 14/patient (median: 13; 95% confidence interval [CI] ). Eleven patients (31.4%) had metastasis to their pelvic lymph nodes. Mean metastasis size was 3.1 mm (median: 2.7 mm; 95%CI mm). Tables 2 and 3 show the distribution of metastatic lymph nodes according to pathologic staging and final Gleason score. The location and number of metastases per anatomic region are shown in Table 4. Of 11 patients with metastasis, 5 (45.5%) had their involved lymph node exclusively outside the obturator fossa and would have been under-staged by a limited dissection template. LNM were in the obturator fossa only in two patients (one bilateral), around the external iliac artery only in two patients, around the internal iliac artery only in two patients, and around the external iliac artery and internal iliac only in one patient. All interventions were accomplished laparoscopically and no conversion was necessary. Complications were limited to two (5.7%) temporary and reversible neurapraxias (ischiatic nerve and obturator nerve), as well as one (2.9%) deep vein thrombosis and two (5.7%) lymphoceles. One lym- Fig. 8 (A) Dissection of the external iliac vessels. (B) 1, common iliac artery; 2, external iliac artery; 3, internal iliac artery; 4, medial umbilical ligament; 5, obturator nerve; 6, external iliac vein; 7, external iliac node packet; 8, peritoneal incision.

6 1352 european urology 52 (2007) Fig. 9 (A) Splitting over the obturator nerve. (B) 1, obturator nerve; 2, external iliac vein; 3, pelvic wall musculature; 4, medial umbilical ligament (retracted medially); 5, obturator node packet. Table 2 Number of metastases according to pathologic stages Pathologic tumor stage No. of patients No. with metastases pt2 18 0/18 (0%) pt /17 (58.8%; CI 35 81%) pt4 0 CI = 95% confidence interval. phocele healed conservatively, and the second was marsupialized laparoscopically. Postoperative PSA follow-up was available up to 2 yr after dissection in 24 patients (68.5%). Of the patients with LNM, three (27.3%) experienced biochemical recurrence and were placed on hormonal treatment. The rest have experienced no recurrence after a mean follow-up of 12.8 mo (median: 9 mo; range: 3 24 mo). None of the patients with negative lymph node dissection have experienced recurrence after a mean follow-up of 6.9 mo (median: 6 mo; range: 3 18 mo). 4. Discussion PLND remains today a controversial issue when it comes to the indication, the extent, and the possible therapeutic value of the dissection. Many studies that have documented the incidence of lymph node metastasis in prostate cancer, before as well as after the PSA era, used a template limited to the obturator fossa [1 6]. Given the lower frequency of LNM that was noted in the PSA era using this limited dissection template (6 9%) [5,23,24], preclinical parameters were assessed to provide an indication of whether to proceed to lymph node dissection or not [4,23,25,26]. This was based on the common belief that PLND in prostate cancer patients undergoing prostatectomy is mainly done for staging and not curative reasons. Studies dating back as far as 25 yr ago have shown, however, that the main drainage of the prostate is to the internal iliac lymph nodes [7]. Furthermore, an increasing body of evidence suggests that more than half of the LNM occur outside Table 3 Number of metastases according to Gleason score Gleason score on prostatectomy specimen No. of patients No. with metastasis 5 2 0/ /14 (7.1%; CI %) /12 (33.3%; CI %) 8 5 4/5 (80%; CI %) 9 2 2/2 (100%) CI = 95% confidence interval. Table 4 Distribution of metastases per anatomic region Mean nodal count per patient (median, 95%CI) 14 (13, ) Metastases per anatomic region External iliac 5/144 (3.5%, CI %) Obturator fossa 6/133 (4.5%, CI 1 8%) Internal iliac 4/49 (8.2%, CI %) Obturator + internal iliac 1/67 (1.5%, CI 0 4.4%) Nonspecified 3/85 (3.5%, CI 0 7.4%) CI = 95% confidence interval.

7 european urology 52 (2007) the obturator fossa [8,19,27], bringing into question the conclusions drawn from previous data. As stated, what defines an extended lymph node dissection is a subject of controversy. Lymph node count has been suggested by some authors as a criterion for separating an extended from a limited dissection [28]. However, given that the node count is not available to the surgeon during the surgical procedure, we do not define an extended or a limited node dissection based on the number of nodes but solely on the template. This is why we include patients who, for instance, have fewer than 10 nodes in our analysis. This being said, our median node count is considered comparable to what is achieved with extended dissections, and patients with 10 lymph nodes or less account for only 13.8% of our population [8,9]. The rate of positive lymph nodes reported in open eplnd varies from 3.2% to 26.2%, depending on the population studied [8,9,27]. Our metastatic lymph nodes rate using laparoscopic eplnd was 31.4%, which is in accordance with studies treating highrisk patients with clinical T2 and T3 disease. We underline, however, the fact that this is a biased incidence related to our indications, because a number of these patients were known to have metastasis in their sentinel lymph node frozen section, which prompted the extended dissection. This may therefore be an overestimate of the incidence of metastasis in a highly selected population. On the other hand, the fact that we analyze patients having positive frozen section along with patients having no sentinel lymph node detected may artifactually decrease the estimated incidence of metastasis. Ideally, these two cohorts, with different risk profiles, should be separately analyzed. Given our limited initial numbers, however, we have decided to analyze them as a single cohort. The concordance of our finding with previously published results may imply that the pooled data of these extreme cohorts may actually represent a fair approximation of the average expected incidence of metastasis. We were able to reproduce the previously reported finding that a significant number of metastasis (namely, 45.5% in this study) were exclusively outside the obturator fossa and would therefore have been missed with a limited dissection. Furthermore, quality assurance reflected by the number of dissected lymph nodes per patient in our population compares favorably to what is published in open series, where median lymph nodes removed per patient varied from 11.6 to 20 [8,9]. Our series also compares well to laparoscopic eplnd series reporting this figure in the literature [29,30]. Our median number of lymph nodes resected was 13 and represents an underestimation of the total number of nodes that could be resected per patient using our technique. This is because we performed extended dissection on only one side in as many as 23 of 35 patients given that these patients were also involved in a sentinel lymph node study. It may be argued that patients in whom unilateral eplnd was performed should not be included in the analysis because the true nodal status in these patients is unknown. Our findings pertaining to sentinel lymph node dissection in prostate cancer have demonstrated, however, that when metastases are present, they exclusively occur in the sentinel node [19]. We therefore believe that no information is lost when eplnd is performed unilaterally in a patient who already had sentinel node dissection on the contralateral side. Although with limited numbers, this series shows that reliance on a PSA cut-off value of 10 as has been suggested in previous studies may still miss a significant number (13.3%) of patients with positive lymph nodes. Although we perform PLND at our institution solely for diagnostic reasons, some studies suggest, albeit with retrospective evidence, that the removal of micrometastasis may be curative in prostate cancer [11 14]. Therefore, 13.3% of false negatives may not be inconsequential. At the beginning of our experience, we attempted to approach laparoscopic eplnd using both transperitoneal and preperitoneal approaches. We soon realized, however, that the feasibility of the procedure relied on the type of surgical exposure that could only be achieved with the transperitoneal approach, especially with regard to the internal iliac vessels dissection. We also feel that placing a drain intraperitoneally at the end of procedure is an additional prophylactic measure against lymphocele formation because it keeps the communication between the intraperitoneal and extraperitoneal spaces patent. These considerations prompted us to adopt an exclusively transperitoneal approach in our subsequent patients. Overall complication rates vary from 4.1% to 22.4% for limited template PLND [2,25] and from 2% to 35% for eplnd [8,27]. Our complication rate in this series was 14.3%, which compares favorably to what is published for extended and even limited template PLND. The major drawbacks of this study are the limited number of patients, the limited follow-up as well as the highly selected patient population. However, our main intention was to show technical feasibility and proof of adequacy using quality control param-

8 1354 european urology 52 (2007) eters such as total lymph node count and complication rates, and to propose a standardized approach that will hopefully allow comparison in future studies. 5. Conclusion We have described a standardized approach to performing extended laparoscopic lymph node dissection in prostate cancer. This approach is feasible, and reproducible and yields comparable results to the open technique. Further studies with follow-up are needed to compare these two techniques. Conflicts of interest There are no commercial interests involved with this article. However, the production of the DVD has been sponsored by Olympus. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at doi: / j.eururo and via com. Subscribers to the printed journal will find the supplementary data attached (DVD). References [1] Fowler JE, Whitmore Jr WF. The incidence and extent of pelvic lymph node metastasis in apparently localized prostate cancer. Cancer 1981;47: [2] McDowel II CG, Johnson JW, Tenney DM, Johnson DE. Pelvic lymphadenectomy for staging clinically localized prostate cancer: indications, complications, and results in 217 cases. Urology 1990;35: [3] Partin AW, Yoo J, Carter HB, et al. The use of prostate specific antigen, clinical stage and Gleason score to predict pathological stage in men with localized prostate cancer. J Urol 1993;150: [4] Bluestein DL, Bostwick DG, Bergstralh EJ, Oesterling JE. Eliminating the need for bilateral pelvic lymphadenectomy in select patients with prostate cancer. J Urol 1994;151: [5] Petros JA, Catalona WJ. Lower incidence of unsuspected lymph node metastases in 521 consecutive patients with clinically localized prostate cancer. J Urol 1992;147: [6] Danella JF, Dekernion JB, Smith RB, Steckel J. The contemporary incidence of lymph node metastases in prostate cancer: implications for laparoscopic lymph node dissection. J Urol 1993;149: [7] Raghavaiah NV, Jordan Jr WP. Prostatic lymphography. J Urol 1979;121: [8] Bader P, Buckhard FC, Markwalder R, Studer UE. Is a limited lymph node dissection an adequate staging procedure for prostate cancer? J Urol 2002;168: [9] Allaf ME, Palapattu GS, Trock BJ, Carter HB, Walsh PC. Anatomical extent of lymph node dissection: impact on men with clinically localized prostate cancer. J Urol 2004;172: [10] Weckermann D, Goppelt M, Dorn R, Wawroschek F, Harzmann R. Incidence of positive pelvic lymph nodes in patients with prostate cancer, a prostate-specific antigen (PSA) level of < or =10 ng/ml and biopsy Gleason score of < or =6, and their influence on PSA progression-free survival after radical prostatectomy. BJU Int 2006;97: [11] Zincke H, Utz DC, Myers RP, Farrow GM, Patterson DE, Furlow WL. Bilateral pelvic lymphadenectomy and radical retropubic prostatectomy for adenocarcinoma of prostate with regional lymph node involvement. Urology 1982;19: [12] Bader P, Burkhard FC, Markwalder R, Studer UE. Disease progression and survival of patients with positive lymph nodes after radical prostatectomy. Is there a chance of cure? J Urol 2003;169: [13] Schmid HP, Mihatsch MJ, Hering F, Rutishauser G. Impact of minimal lymph node metastasis on long-term prognosis after radical prostatectomy. Eur Urol 1997;31:11 6. [14] Cheng L, Zincke H, Blute ML, Bergstralh EJ, Scherer B, Bostwick DG. Risk of prostate carcinoma death in patients with lymph node metastasis. Cancer 2001;91: [15] Joslyn SA, Konety BR. Impact of extent of lymphadenectomy on survival after radical prostatectomy for prostate cancer. Urology 2006;68: [16] Gershman A, Daykhovsky L, Chandra M, Danoff D, Grundfest WS. Laparoscopic pelvic lymphadenectomy. J Laparoendosc Surg 1990;1:63 8. [17] Griffith DP, Schuessler WW, Nickell KG, Meaney JT. Laparoscopic pelvic lymphadenectomy for prostatic adenocarcinoma. Urol Clin North Am 1992;19: [18] Beer M, Staehler G, Dorsam J. Laparoscopic pelvic lymphadenectomy. Indications, technique, initial results. Chirurg 1991;62: [19] Jeschke S, Nambirajan T, Leeb K, Ziegerhofer J, Sega W, Janetschek G. Detection of early lymph node metastases in prostate cancer by laparoscopic radioisotope guided sentinel lymph node dissection. J Urol 2005;173: [20] Amling CL, Bergstralh LH, Blute ML, Slezak JM, Zincke H. Defining prostate specific antigen progression after radical prostatectomy: what is the most appropriate cut point? J Urol 2003;165: [21] Simmons MN, Stephenson AJ, Klein EA. Natural history of biochemical recurrence after radical prostatectomy: risk assessment for secondary therapy. Eur Urol 2007; 51: [22] Stephenson AJ, Kattan MW, Eastham JA, et al. Defining biochemical recurrence of prostate cancer after radical

9 european urology 52 (2007) prostatectomy: a proposal for a standardized definition. J Clin Oncol 2006;24: [23] Bishoff JT, Reyes A, Thompson IM, et al. Pelvic lymphadenectomy can be omitted in selected patients with carcinoma of the prostate: development of a system of patient selection. Urology 1995;45: [24] Partin AW, Kattan KW, Subong EN, et al. Combination of prostate-specific antigen, clinical stage, and Gleason score to predict pathological stage of localized prostate cancer. A multi-institutional update. JAMA 1998;277: [25] Campbell SC, Klein EA, Levin HS, Piedmonte MR. Open pelvic lymph node dissection for prostate cancer: a reassessment. Urology 1995;46: [26] Bhatta-Dhar N, Reuther AM, Zippe C, Klein EA. No difference in six-year biochemical failure rates with or without pelvic lymph node dissection during radical prostatectomy in low-risk patients with localized prostate cancer. Urology 2004;63: [27] Heidenreich A, Varga Z, VonKnobloch R. Extended pelvic lymphadenectomy in patients undergoing radical prostatectomy: high incidence of lymph node metastasis. J Urol 2002;167: [28] Briganti A, Chun FK-H, Salonia A, et al. Complications and other surgical outcomes associated with extended pelvic lymphadenectomy in men with localized prostate cancer. Eur Urol 2006;50: [29] Touijer K, Guillonneau B. Laparoscopic radical prostatectomy: a critical analysis of surgical quality. Eur Urol 2006;49: [30] Wyler SF, Sulser T, Seifert HH, et al. Laparoscopic extended pelvic lymph node dissection for high risk prostate cancer. Urology 2006;68: Editorial Comment on: Laparoscopic Extended Pelvic Lymph Node Dissection for Prostate Cancer: Description of the Surgical Technique and Initial Results Pierre I. Karakiewicz Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Quebec, Canada H2X 3J4 pierre.karakiewicz@umontreal.ca Lattouf et al address the issue of lymph node metastases in men with clinically localized prostate cancer (PCa) and confirm the validity of extended pelvic lymphadenectomy in patients undergoing laparoscopic radical prostatectomy [1]. In clinically localized PCa, lymphadenectomy continues to represent a topic of interest and of renewed controversy. Studer and colleagues sensitized the urologic community about the unreliability of limited pelvic lymph node dissection in localized PCa nodal staging [2]. They and others have convincingly demonstrated that the obturator fossa does not represent a safe sentinel site for nodal metastases in all men, regardless of clinical stage, biopsy Gleason sum, and pretreatment serum prostate-specific antigen level. Instead, in at least a proportion of patients, the metastatic spread to lymph nodes occurs through anatomic skip lesions, without affecting the obturator fossa. Studer and colleagues also hinted at a possible survival benefit related to extended lymphadenectomy. However, current data can only confirm a stage migration, when an extended lymphadenectomy is performed instead of a more limited one. The effect of this stage shift spuriously appears to improve the prognosis of men with multiple negative nodes. Indeed, the prognosis is invariably better when more nodes are removed, even in the presence of positive nodes. However, this is exclusively due to stage migration and applies to PCa as well as other malignancies. Briganti and colleagues built on the novel and important findings describing the prevalence and distribution of nodal metastases at radical prostatectomy [3]. They refined the approach to pelvic lymphadenectomy. Specifically, they demonstrated that lymphadenectomies need not be performed in all men. Moreover, they have shown that the decision to perform a lymphadenectomy and the decision about its extent can be tailored according to the individual risk of nodal metastases and their predicted distribution. Nomograms predicting the likelihood of nodal metastases according to the anatomic extent of lymph node dissection or the number of removed and examined lymph nodes represent highly useful tools that can guide the physician in the process of patient selection in the most evidence-based, individualized, and risk-tailored fashion (www. nomogram.org). However, despite the novelty and the controversy, many advances in the field of nodal staging are frequently greeted with initial distrust. A central argument of many clinicians with regard to the importance of pathologic diagnosis of nodal metastases relates to its questionable impact on clinical natural history of treated cancer. What clinicians question the most is the practical impact of positive nodes at radical prostatectomy on patient management. This attitude stems from clinical observations indicating that 25% of men with established nodal metastases will be free of biochemical recurrence 5 yr after

10 1356 european urology 52 (2007) radical prostatectomy, without the use of any secondary therapy [4]. However, among all highrisk patients those with nodal metastases at radical prostatectomy represent the highest risk stratum. Therefore, is radical prostatectomy with delayed intervention the best that we can offer to the 75% who will have treatment failure within 5 yr after radical prostatectomy? Messing et al provided initial highly encouraging findings regarding this particularly high-risk cohort and recently reconfirmed their findings with an updated follow-up. Their results demonstrate an important overall and disease-specific survival benefit, when androgen-deprivation therapy is initiated immediately after radical prostatectomy instead of at the time of clinical disease relapse. Are these survival gains important? The answer is again yes. At 7 yr after prostatectomy, the absolute decrease in causespecific mortality exceeded 30% and the absolute decrease in overall mortality was close to 25%. These findings so far have not been replicated by any other therapeutic modality for patients with high-risk PCa. For example, two contemporary trials of adjuvant radiotherapy for men with pathologically unfavorable PCa at radical prostatectomy failed to demonstrate any statistically significant survival benefit [5]. Therefore, the results of the Messing et al study are fundamental because they indicate in a randomized and controlled fashion that cause-specific and overall survival can be improved in a highly clinically meaningful fashion. However, the most accurate pathologic nodal staging at radical prostatectomy is required to obtain the necessary staging information. Therefore, identification of candidates for nodal staging using nomograms and nomogramguided risk-adjusted approaches to pathologic staging of nodal metastases should continue to represent a central theme in the management of all patients with clinically localized PCa. References [1] Lattouf J-B, Beri A, Jeschke S, Sega W, Leeb K, Janetschek G. Laparoscopic extended pelvic lymph node dissection for prostate cancer: description of the surgical technique and initial results. Eur Urol 2007;52: [2] Bader P, Burkhard FC, Markwalder R, Studer UE. Is a limited lymph node dissection an adequate staging procedure for prostate cancer? J Urol 2002;168: [3] Briganti A, Chun FK, Salonia A, et al. Validation of a nomogram predicting the probability of lymph node invasion among patients undergoing radical prostatectomy and an extended pelvic lymphadenectomy. Eur Urol 2006;49: [4] Messing EM, Manola J, Yao J, et al., Eastern Cooperative Oncology Group study. EST 3886: Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy. Lancet Oncol 2006;7: [5] Thompson Jr IM, Tangen CM, Paradelo J, et al. Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial. JAMA 2006;296: DOI: /j.eururo DOI of original article: /j.eururo Editorial Comment on: Laparoscopic Extended Pelvic Lymph Node Dissection for Prostate Cancer: Description of the Surgical Technique and Initial Results Fernando J. Bianco Jr. Department of Urology, George Washington University, Washington, DC, USA biancof@gwu.edu This interesting study proposes a surgical technique for an extended laparoscopic pelvic lymph node dissection (PLND) for men with prostate cancer [1]. However, under a cancer control paradigm we do take issue with the concept of extended versus limited dissection. It seems clear in the literature (references 2 6 in the report) that the limited boundaries are well understood and commonly performed, yet fall short because they may identify as much as they miss [2]. Anatomic principles based on historical lymphographic studies suggest that the lymphatic drainage of the prostate flows to nodal tissue contained in the adjacent areas of the inner pelvis. Thus, what is labeled today as extended dissection may represent an appropriate PLND. We should excise no less. This is so unless we test a hypothesis in prospective protocols that seek better patient characterization for this procedure as those pursued in recent evaluations by these investigators and others assessing the value of

11 european urology 52 (2007) sentinel nodes in prostate cancer [1,3]. Nonetheless, we may ask what represents an appropriate anatomic PLND. Clearly, the boundaries suggested in Fig. 1 by this study from Lattouf et al [1] are different from the more established description by Bader et al [2]. These markedly different landmarks handicap scientific reproducibility. Naming or comparing surgical techniques with distinctive anatomic goals makes no sense to us. We have recently shown that in men with prostate cancer, cancer control outcomes depend not only on the cancer characteristics but also on how we perform the surgical procedure, a surrogate of the surgeon s perspective or personal bias, which is acquired from experience to a certain degree. What are the key elements embodied in optimal surgery? Maturing data from larger cohorts have taught us that pelvic node dissections carry much more than prognostic information [2,4,5]. They are curative for a significant number of patients [2,4,5]. Hope shall not be lost if we find a positive node. In fact, survival depends on the number of positive nodes encountered [2], the node-positive density [5], and, in the absence of positive nodes, the number of negative nodes [4]. Historical studies recognized how the lymphatic drainage transits first through the hypogastric tributaries. This region, described as level 3 by Bader et al, harbored exclusive metastases in 19% of their positive nodes [2], an area with compromised anatomic access, greater potential for bleeding, and imperative of surgical exposure. The proposed laparoscopic technique would have spared this nodal tissue and perhaps discounted it as a possible source of cancer recurrence. Although we celebrate the methodology and clear definitions of this well-performed study, we advocate for a standard of care, one that is fair to a patient s interests and cancer control objectives, yet not tailored to a particular technique but otherwise suitable. References [1] Lattouf J-B, Beri A, Jeschke S, Sega W, Leeb K, Janetschek G. Laparoscopic extended pelvic lymph node dissection for prostate cancer: description of the surgical technique and first results. Eur Urol 2007;52: [2] Bader P, Burkhard FC, Markwalder R, Studer UE. Is a limited lymph node dissection an adequate staging procedure for prostate cancer? J Urol 2002;168:514 8, discussion 518. [3] Warncke SH, Mattei A, Fuechsel FG, Z Brun S, Krause T, Studer UE. Detection rate and operating time required for g probe-guided sentinel lymph node resection after injection of technetium-99m nanocolloid into the prostate with and without preoperative imaging. Eur Urol 2007;52: [4] Masterson TA, Bianco Jr FJ, Vickers AJ, et al. The association between total and positive lymph node counts, and disease progression in clinically localized prostate cancer. J Urol 2006;175:1320 4, discussion [5] Palapattu GS, Allaf ME, Trock BJ, Epstein JI, Walsh PC. Prostate specific antigen progression in men with lymph node metastases following radical prostatectomy: results of long-term followup. J Urol 2004;172: DOI: /j.eururo DOI of original article: /j.eururo