Urological Oncology 94 Urology Journal Vol 5 No 2 Spring 2008 Separate Submission of Standard Lymphadenectomy in 6 Packets Versus En Bloc Lymphadenectomy in Bladder Cancer M Hammad Ather, Zaheer Alam, Anila Jamshaid, Khurram M Siddiqui, M Nasir Sulaiman Introduction: Our aim was to evaluate detection of nodal metastasis during radical cystectomy with standard pelvic lymph node dissection versus en bloc lymphadenectomy for the treatment of bladder cancer. Materials and Methods: Hospital records of a total of 77 patients with radical cystectomy and either standard pelvic lymph node dissection or en bloc lymphadenectomy were reviewed. Nodal dissection specimens during standard lymphadenectomy were sent for pathology examination in 6 separate containers marked as external iliac, internal iliac, and obturator groups from both sides. En bloc dissection specimens were sent in 2 containers marked as the right and the left pelvic nodes. Clinical and pathological findings of these two groups were compared in terms of the number of dissected lymph nodes, number of nodes with metastasis, lymph node density, and clinical outcomes. Results: There were 34 patients with standard lymph node dissection and 43 with en bloc lymphadenectomy (anterior pelvic exenteration). Age, sex, duration of the disease, number of transurethral resections prior to cystectomy, pathological grade at cystectomy, and stage of the primary tumor were comparable in the two groups of patients. The median numbers of nodes removed per patient were 15.5 (range, 4 to 48) and 7.0 (range, 1 to 24) in those with standard and en bloc lymphadenectomy, respectively (P < .001). Nodal involvement was detected in 10 (29.4%) and 9 (20.9%) patients, respectively (P = .43). Conclusion: Although nodal involvement was not significantly different between the two groups, standard lymphadenectomy submitted in 6 different containers significantly improved the nodal yield over en bloc resection. Obturator nodes were the most commonly involved nodes in our study. Urol J. 2008;5:94-8. www.uj.unrc.ir Keywords: urinary bladder neoplasms, cystectomy, lymph node excision Department of Surgery, Aga Khan University, Karachi, Pakistan Corresponding Author: M Hammad Ather, MD PO Box 3500, Stadium Road, Karachi 74800, Pakistan Tel: +92 21 486 4778 Fax: +92 21 493 4294 E-mail: hammad.ather@aku.edu Received December 2007 Accepted April 2008 INTRODUCTION Transitional cell carcinoma (TCC) of the bladder originates from the mucosa, invades the lamina propria, and involves the muscularis propria, perivesical fat, and pelvic structures with increasing incidence of lymph node involvement during progression.(1) On cystectomy, 14% to 28 % of the patients show evidence of lymph node metastasis.(2) Radical cystectomy (RC) is the standard management of high-grade and muscle-invasive bladder tumors. Bilateral pelvic lymphadenectomy is now an Standard versus En Bloc Lymphadenectomy in Bladder Cancer—Ather et al Urology Journal Vol 5 No 2 Spring 2008 95 essential part of RC. A combination of these two provides excellent local control and long-term survival rate for most of the patients with tumors in stage pT2 or higher.(3,4) Thus, accurate staging is decisive in terms of choosing the treatment option and reducing local recurrence. Preoperative imaging modalities may miss microscopic nodal metastasis in up to 70% of the patients.(5) Lymph node involvement is associated with increased risk of local recurrence and disease progression with survival rates varying from 20% to 40% in patients with and without lymph node metastasis, respectively.(6,7) The practice of lymphadenectomy is not standardized. It has been shown that the number of nodes retrieved could vary from 0 to 53 per patient.(8) Recent studies suggest that both the number of nodes removed and the method of submission of lymph node specimens affect the treatment outcome.(3, 9-11) Some recent papers have also indicated that the lymph node specimens separately retrieved and submitted for pathology have a greater number of nodes compared to en bloc resection.(9-11) Studies have shown that the incidence of positive lymph nodes increased with higher stage, higher pathological grade, and greater number of transurethral resections prior to RC.(10-12) In the present study, we sought to identify if there was a difference in the number of nodes retrieved between separately retrieved and submitted pathologic specimens and specimens from en bloc resection. MATERIALS AND METHODS Hospital records of all patients with TCC of the bladder treated by RC or anterior pelvic exenteration (APE) at our institution between 1995 and 2007 were retrospectively studied. During this period, 95 patients had undergone RC or APE for primary bladder cancer. We excluded 18 patients because their lymph nodes could not been evaluated. The hospital was not a referral center for oncological surgery. There are 3 trained oncological urologists and all types of urinary diversions including orthotopic bladder replacements are performed. Of 77 patients, 34 (44.2%) had undergone standard lymphadenectomy (group 1; lymph nodes submitted in 6 separate nodal packets) and 43 (55.8%) had undergone en bloc dissection (group 2). The extent and operative field in the two groups were similar. The field of standard lymph node dissection extends caudally, up to the lacunar ligament; cranially, to the angle of Marcille; laterally, to the genitofemoral nerve; and medially, up to the obturator nerve. Nodal dissection specimens during standard lymphadenectomy had been sent for pathology examination in 6 separate containers marked as external iliac, internal iliac, and obturator groups from both sides. En bloc dissection specimens had been sent in 2 containers marked as the right and the left pelvic nodes. The patients in the two surgical groups were compared in terms of the number of dissected lymph nodes, number of nodes with metastasis, lymph node density, and other clinical outcomes. Lymph node density was defined as the ratio of positive nodes for metastasis to the total number of nodes examined. Operative mortality was defined as death within 30 days after the procedure. Data were analyzed using the SPSS software (Statistical Package for the Social Sciences, version 15.0, SPSS Inc, Chicago, Ill, USA). Continuous variables were compared between the groups using the independent sample t test or the Mann Whitney U test. The chi- square test and the Fischer exact test were used to compare categorical and dichotomous variables. A P value less than .05 was considered significant. RESULTS Of 77 patients with TCC of the bladder, 67 (87.0%) were men and 10 (13.0%) were women. The two groups were comparable in terms of age, sex, primary tumor stage, grade of the tumor, duration of the disease, and number of transurethral resections (Table 1). The median number of nodes removed per patient were 15.5 (range, 4 to 48) in group 1 and 7 (range, 1 to 24) in group 2 (P < .001). There were 10 patients (29.2%) and 9 patients (20.9%) with involved nodes in groups 1 and 2, respectively (P = .43). The obturator lymph nodes were the most commonly involved nodes followed by internal and external iliac node groups in patients Standard versus En Bloc Lymphadenectomy in Bladder Cancer—Ather et al 96 Urology Journal Vol 5 No 2 Spring 2008 of group 1 (Figure). Lymph node density was significantly higher in the patients of group 1 than those of group 2 (P < .001; Table 2). Early complications, including lymphocele, were noted in 7 patients (20.6%) in group 1 and 4 (9.3%) in group 2; however, none of the patient required surgical intervention. No other complication or peri-operative death was attributed directly to the lymph node dissection in neither of the groups (Table 2). DISCUSSION Lymph node metastasis is detected in 14% to 28% of the patients undergoing pelvic lymphadenectomy during RC for bladder cancer.(2) It is associated with an increased risk of local recurrence, regional disease progression, and overall poorer outcome. Extended standard lymphadenectomy is important for accurate Surgical Treatment Characteristics Standard Lymphadenectomy(Group 1) En Bloc Cystectomy (Group 2) P Number of patients 34 (44.2) 43 (55.8) Mean age, y 56.5 ± 13.3 64.0 ± 12.4 .51 Sex Male 28 (82.4) 39 (90.7) Female 6 (17.6) 4 (9.3) .32 Duration of disease, d† 76.0 ± 946.8 147.0 ± 927.0 .97 Tumor stage T0 3 (8.8) 4 (9.3) T1 1 (2.9) 2 (4.7) T2 16 (47.1) 23 (53.5) T3 9 (26.5) 6 (14) T4 5 (14.7) 8 (18.6) .74 Tumor grade 1 0 1 (2.3) 2 5 (14.7) 12 (27.9) 3 29 (85.3) 30 (69.8) .19 Number of resections 1.0 ± 1.0 1.0 ± 1.1 .90 Table 1. Demographic and Clinical Profile of Patients With Bladder Cancer Who Underwent Either Radical Cystectomy and Standard Lamyphadenectomy or En Bloc Cystectomy* *Values in parentheses are percents. †Duration of disease was defined as the time from diagnosis to cystectomy. Location of 46 metastatic nodes in 34 patients with anatomical dissection (standard lymphadenectomy). IIL indicates internal iliac lymph node; EIL, external iliac lymph node; and OL, obturator lymph node. Surgical Treatment Characteristics Standard Lymphadenectomy(Group 1) En Bloc Cystectomy (Group 2) P Median number of removed nodes 15.5 7 < .001 Patients with involved lymph nodes 10 (29.4) 9 (20.9) .43 Median lymph node density, % 23.5 11.0 < .001 Operative mortality 1 (2.9) 1 (2.3) .70 Patients with early complications 7 (20.6) 4 (9.3) .16 Table 2. Outcomes of Standard Lamyphadenectomy and En Bloc Cystectomy Standard versus En Bloc Lymphadenectomy in Bladder Cancer—Ather et al Urology Journal Vol 5 No 2 Spring 2008 97 staging and provides direct survival benefit.(2) Recent evidence has shown that node involvement is a significant and independent prognostic factor.(3-5) A growing body of evidence suggests that an extended lymph node dissection may provide prognostic information and therapeutic benefits for patients with or without lymph node involvement undergoing RC for TCC. Boundaries of the lymphadenectomy are still a subject of controversy. Abol-Enein and colleagues reported that extended lymphadenectomy up to the origin of the inferior mesenteric vessels showed 37% and 60% bilateral and unilateral node involvement, respectively.(13) Dissection of only internal iliac nodes will miss 85% of positive nodes, whereas dissection of the internal and external iliac and obturator nodes will pick two-thirds of the nodes. Dissection up the aortic bifurcation picks four-fifth of the nodes.(13) Guidelines for the treatment of muscle-invasive bladder cancer by the European Association of Urology recommend limited pelvic node dissection, consisting of removal of the tissue in the obturator fossa in patients undergoing surgery with a curative intent.(14) Several authors have noted an improved 5-year survival rate with extensive pelvic lymph node dissection in the patients with node-involved bladder cancer.(5,15) Herr and colleagues studied the number of nodes removed and its effect on the outcome of the patient after RC.(3) They found that a minimum of 9 nodes was needed to be examined to accurately assess nodal involvement. They also found that survival improved in both patients with and without node involvement as the number of the removed nodes increased. They also evaluated the impact of submitting nodes en bloc or as separate packages and suggested that submitting nodes as separate packages not only is easier, but also optimizes the evaluation and number of the lymph nodes retrieved.(3) Some studies indicate that lymphadenectomy in combination with RC can cure a small fraction of node-positive patients.(9) CONCLUSION We found that the number of the nodes retrieved per specimen increases significantly if dissection and submission of the nodes is done in the anatomically defined areas rather than en bloc submission. CONFLICT OF INTEREST None declared. ACKNOWLEDGEMENT We would like to thank Dr Syed Iqbal Azam, Assistant Professor, Coordinator, Statistical Consulting Services, Community Health Sciences, Aga Khan University. REFERENCES 1. Ather MH, Fatima S, Sinanoglu O. Extent of lymphadenectomy in radical cystectomy for bladder cancer. World J Surg Oncol. 2005;3:43. 2. Vieweg J, Gschwend JE, Herr HW, Fair WR. 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