The Role of Pelvic Lymphadenectomy at the Time of Radical Cystectomy for Bladder Cancer

  • Samuel D. Kaffenberger
  • Todd M. MorganEmail author
  • Anne K. Schuckman


Pelvic lymphadenectomy at the time of radical cystectomy is a standard therapeutic adjunct which has been shown to improve both staging and survival for patients with muscle-invasive bladder cancer. However, there exists great controversy in determining the optimal extent of lymphadenectomy as well as in defining appropriate quality metrics for assessing the completeness of lymph node dissection. In this chapter, the anatomy of pelvic lymphadenectomy templates is defined, the available evidence in support of extended lymphadenectomy is summarized and appraised, and the role of lymphadenectomy in patients with clinical node-positive disease is visited. We also critically evaluate the utilization of lymph node counts as a surrogate for lymphadenectomy completeness and address possible alternatives. Due to the intrinsic limitations of observational studies, it is not yet certain what the optimal extent of lymphadenectomy is and ongoing clinical trials to address these questions are therefore reviewed.


Bladder cancer Muscle-invasive Pelvic lymphadenectomy Radical cystectomy Staging Lymphadenectomy extent Lymph node count Extended pelvic lymphadenectomy Lymph node mapping Robotic surgery 


  1. 1.
    Stein J, Lieskovsky G, Cote R, Groshen S, Feng A, Boyd S, et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol. 2001;19:666–75.PubMedGoogle Scholar
  2. 2.
    Herr HW. Extent of surgery and pathology evaluation has an impact on bladder cancer outcomes after radical cystectomy. Urology. 2003;61:105–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Leissner J, Hohenfellner R, Thüroff JW, Wolf HK. Lymphadenectomy in patients with transitional cell carcinoma of the urinary bladder; significance for staging and prognosis. BJU Int. 2000;85:817–23.PubMedCrossRefGoogle Scholar
  4. 4.
    Herr HW, Bochner BH, Dalbagni G, Donat SM, Reuter VE, Bajorin DF. Impact of the number of lymph nodes retrieved on outcome in patients with muscle invasive bladder cancer. J Urol. 2002;167:1295–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Karl A, Carroll PR, Gschwend JE, Knüchel R, Montorsi F, Stief CG, 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.PubMedCrossRefGoogle Scholar
  6. 6.
    Stein JP. Lymphadenectomy in bladder cancer: how high is “high enough”? Urol Oncol. 2006;24:349–55.PubMedCrossRefGoogle Scholar
  7. 7.
    Dorin RP, Daneshmand S, Eisenberg MS, Chandrasoma S, Cai J, Miranda G, et al. Lymph node dissection technique is more important than lymph node count in identifying nodal metastases in radical cystectomy patients: a comparative mapping study. Eur Urol. 2011;60:946–52.PubMedCrossRefGoogle Scholar
  8. 8.
    Zehnder P, Studer UE, Skinner EC, Dorin RP, Cai J, Roth B, et al. Super extended versus extended pelvic lymph node dissection in patients undergoing radical cystectomy for bladder cancer: a comparative study. J Urol. 2011;186:1261–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Bochner BH, Cho D, Herr HW, Donat M, Kattan MW, Dalbagni G. Prospectively packaged lymph node dissections with radical cystectomy: evaluation of node count variability and node mapping. J Urol. 2004;172:1286–90.PubMedCrossRefGoogle Scholar
  10. 10.
    Shabsigh A, Korets R, Vora KC, Brooks CM, Cronin AM, Savage C, et al. Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol. 2009;55:164–74.PubMedCrossRefGoogle Scholar
  11. 11.
    Lowrance WT, Rumohr JA, Chang SS, Clark PE, Smith JA, Cookson MS. Contemporary open radical cystectomy: analysis of perioperative outcomes. J Urol. 2008;179:1313–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Leissner J, Ghoneim MA, Abol-Enein H, Thüroff JW, Franzaring L, Fisch M, et al. Extended radical lymphadenectomy in patients with urothelial bladder cancer: results of a prospective multicenter study. J Urol. 2004;171:139–44.PubMedCrossRefGoogle Scholar
  13. 13.
    Miocinovic R, Gong MC, Ghoneim IA, Fergany AF, Hansel DE, Stephenson AJ. Presacral and retroperitoneal lymph node involvement in urothelial bladder cancer: results of a prospective mapping study. J Urol. 2011;186(4):1269–73.PubMedCrossRefGoogle Scholar
  14. 14.
    Vazina A, Dugi D, Shariat SF, Evans J, Link R, Lerner SP. Stage specific lymph node metastasis mapping in radical cystectomy specimens. J Urol. 2004;171:1830–4.PubMedCrossRefGoogle Scholar
  15. 15.
    Jensen JB, Ulhøi BP, Jensen KM-E. Lymph node mapping in patients with bladder cancer undergoing radical cystectomy and lymph node dissection to the level of the inferior mesenteric artery. BJU Int. 2010;106:199–205.PubMedCrossRefGoogle Scholar
  16. 16.
    Liedberg F, Chebil G, Davidsson T, Gudjonsson S, Månsson W. Intraoperative sentinel node detection improves nodal staging in invasive bladder cancer. J Urol. 2006;175:84–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Sherif A, Garske U, de La Torre M, Thörn M. Hybrid SPECT-CT: an additional technique for sentinel node detection of patients with invasive bladder cancer. Eur Urol. 2006;50:83–91.PubMedCrossRefGoogle Scholar
  18. 18.
    Roth B, Wissmeyer MP, Zehnder P, Birkhäuser FD, Thalmann GN, Krause TM, et al. A new multimodality technique accurately maps the primary lymphatic landing sites of the bladder. Eur Urol. 2010;57:205–11.PubMedCrossRefGoogle Scholar
  19. 19.
    Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC cancer staging handbook. 7th ed. New York, NY: Springer; 2010.Google Scholar
  20. 20.
    Konety BR, Joslyn SA, O’Donnell MA. Extent of pelvic lymphadenectomy and its impact on outcome in patients diagnosed with bladder cancer: analysis of data from the Surveillance, Epidemiology and End Results Program data base. J Urol. 2003;169:946–50.PubMedCrossRefGoogle Scholar
  21. 21.
    May M, Herrmann E, Bolenz C, Brookman-May S, Tiemann A, Moritz R, et al. Association between the number of dissected lymph nodes during pelvic lymphadenectomy and cancer-specific survival in patients with lymph node-negative urothelial carcinoma of the bladder undergoing radical cystectomy. Ann Surg Oncol. 2011;18:2018–25.PubMedCrossRefGoogle Scholar
  22. 22.
    Wright JL, Lin DW, Porter MP. The association between extent of lymphadenectomy and survival among patients with lymph node metastases undergoing radical cystectomy. Cancer. 2008;112:2401–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Herr HW, Faulkner JR, Grossman HB, Natale RB, DeVere White R, Sarosdy MF, et al. Surgical factors influence bladder cancer outcomes: a cooperative group report. J Clin Oncol. 2004;22:2781–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Brunocilla E, Pernetti R, Schiavina R, Borghesi M, Vagnoni V, Rocca GC, et al. The number of nodes removed as well as the template of the dissection is independently correlated to cancer-specific survival after radical cystectomy for muscle-invasive bladder cancer. Int Urol Nephrol. 2013;45:711–9.Google Scholar
  25. 25.
    Morgan TM, Barocas DA, Penson DF, Chang SS, Ni S, Clark PE, et al. Lymph node yield at radical cystectomy predicts mortality in node-negative and not node-positive patients. Urology. 2012;80:632–40.PubMedCrossRefGoogle Scholar
  26. 26.
    Koppie TM, Vickers AJ, Vora K, Dalbagni G, Bochner BH. Standardization of pelvic lymphadenectomy performed at radical cystectomy: can we establish a minimum number of lymph nodes that should be removed? Cancer. 2006;107:2368–74.PubMedCrossRefGoogle Scholar
  27. 27.
    Gilbert SM. Separating surgical quality from causality–gaining perspective in the debate on lymph node count and extent of lymphadenectomy. Cancer. 2008;112:2331–3.PubMedCrossRefGoogle Scholar
  28. 28.
    Bochner BH, Herr HW, Reuter VE. Impact of separate versus en bloc pelvic lymph node dissection on the number of lymph nodes retrieved in cystectomy specimens. J Urol. 2001;166:2295–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Parkash V, Bifulco C, Feinn R, Concato J, Jain D. To count and how to count, that is the question: interobserver and intraobserver variability among pathologists in lymph node counting. Am J Clin Pathol. 2010;134:42–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Davies JD, Simons CM, Ruhotina N, Barocas DA, Clark PE, Morgan TM. Anatomic basis for lymph node counts as measure of lymph node dissection extent: a cadaveric study. Urology. 2013;81:358–63.PubMedCrossRefGoogle Scholar
  31. 31.
    Kassouf W, Agarwal PK, Herr HW, Munsell MF, Spiess PE, Brown GA, et al. Lymph node density is superior to TNM nodal status in predicting disease-specific survival after radical cystectomy for bladder cancer: analysis of pooled data from MDACC and MSKCC. J Clin Oncol. 2008;26:121–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Bruins HM, Huang GJ, Cai J, Skinner DG, Stein JP, Penson DF. Clinical outcomes and recurrence predictors of lymph node positive urothelial cancer after cystectomy. J Urol. 2009;182:2182–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Stein JP, Cai J, Groshen S, Skinner DG. Risk factors for patients with pelvic lymph node metastases following radical cystectomy with en bloc pelvic lymphadenectomy: concept of lymph node density. J Urol. 2003;170:35–41.PubMedCrossRefGoogle Scholar
  34. 34.
    Herr HW. Superiority of ratio based lymph node staging for bladder cancer. J Urol. 2003;169:943–5.PubMedCrossRefGoogle Scholar
  35. 35.
    Herr H. The concept of lymph node density—is it ready for clinical practice? J Urol. 2007;177:1273–6.PubMedCrossRefGoogle Scholar
  36. 36.
    Wiesner C, Salzer A, Thomas C, Gellermann-Schultes C, Gillitzer R, Hampel C, et al. Cancer-specific survival after radical cystectomy and standardized extended lymphadenectomy for node-positive bladder cancer: prediction by lymph node positivity and density. BJU Int. 2009;104:331–5.PubMedCrossRefGoogle Scholar
  37. 37.
    Tarin TV, Power NE, Ehdaie B, Sfakianos JP, Silberstein JL, Savage CJ, et al. Lymph node-positive bladder cancer treated with radical cystectomy and lymphadenectomy: effect of the level of node positivity. Eur Urol. 2012;61:1025–30.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Jensen JB, Ulhøi BP, Jensen KM-E. Evaluation of different lymph node (LN) variables as prognostic markers in patients undergoing radical cystectomy and extended LN dissection to the level of the inferior mesenteric artery. BJU Int. 2012;109:388–93.PubMedCrossRefGoogle Scholar
  39. 39.
    Dhar NB, Klein EA, Reuther AM, Thalmann GN, Madersbacher S, Studer UE. Outcome after radical cystectomy with limited or extended pelvic lymph node dissection. J Urol. 2008;179:873–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Abol-Enein H, Tilki D, Mosbah A, El-Baz M, Shokeir A, Nabeeh A, et al. Does the extent of lymphadenectomy in radical cystectomy for bladder cancer influence disease-free survival? A prospective single-center study. Eur Urol. 2011;60:572–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Morgan TM, Kaffenberger SD, Cookson MS. Surgical and chemotherapeutic management of regional lymph nodes in bladder cancer. J Urol. 2012;188:1081–8.PubMedCrossRefGoogle Scholar
  42. 42.
    Marín-Aguilera M, Mengual L, Burset M, Oliver A, Ars E, Ribal MJ, et al. Molecular lymph node staging in bladder urothelial carcinoma: impact on survival. Eur Urol. 2008;54:1363–72.PubMedCrossRefGoogle Scholar
  43. 43.
    Kurahashi T. Detection of micrometastases in pelvic lymph nodes in patients undergoing radical cystectomy for focally invasive bladder cancer by real-time reverse transcriptase-pcr for cytokeratin 19 and uroplakin II. Clin Cancer Res. 2005;11:3773–7.PubMedCrossRefGoogle Scholar
  44. 44.
    Baltaci S, Adsan O, Ugurlu O, Aslan G, Can C, Gunaydin G, et al. Reliability of frozen section examination of obturator lymph nodes and impact on lymph node dissection borders during radical cystectomy: results of a prospective multicentre study by the Turkish Society of Urooncology. BJU Int. 2011;107:547–53.PubMedCrossRefGoogle Scholar
  45. 45.
    Ugurlu O, Adsan O, Tul M, Kosan M, Inal G, Cetinkaya M. Value of frozen sections of lymph nodes in pelvic lymphadenectomy in patients with invasive bladder tumor. Int J Urol. 2006;13:699–702.PubMedCrossRefGoogle Scholar
  46. 46.
    Herr HW, Donat SM, Bajorin DF. Post-chemotherapy surgery in patients with unresectable or regionally metastatic bladder cancer. J Urol. 2001;165:811–4.PubMedCrossRefGoogle Scholar
  47. 47.
    Nieuwenhuijzen JA, Bex A, Meinhardt W, Kerst JM, Schornagel JH, van Tinteren H, et al. Neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin for histologically proven lymph node positive bladder cancer. J Urol. 2005;174:80–5.PubMedCrossRefGoogle Scholar
  48. 48.
    Dimopoulos MA, Finn L, Logothetis CJ. Pattern of failure and survival of patients with metastatic urothelial tumors relapsing after cis-platinum-based chemotherapy. J Urol. 1994;151:598–600.PubMedGoogle Scholar
  49. 49.
    Sweeney P, Millikan R, Donat M, Wood CG, Radtke AS, Pettaway CA, et al. Is there a therapeutic role for post-chemotherapy retroperitoneal lymph node dissection in metastatic transitional cell carcinoma of the bladder? J Urol. 2003;169:2113–7.PubMedCrossRefGoogle Scholar
  50. 50.
    Li K, Lin T, Fan X, Xu K, Bi L, Duan Y, et al. Systematic review and meta-analysis of comparative studies reporting early outcomes after robot-assisted radical cystectomy versus open radical cystectomy. Cancer Treat Rev. 2013;39:551–60.PubMedCrossRefGoogle Scholar
  51. 51.
    Hellenthal NJ, Hussain A, Andrews PE, Carpentier P, Castle E, Dasgupta P, et al. Lymphadenectomy at the time of robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium. BJU Int. 2011;107:642–6.PubMedCrossRefGoogle Scholar
  52. 52.
    Nix J, Smith A, Kurpad R, Nielsen ME, Wallen EM, Pruthi RS. Prospective randomized controlled trial of robotic versus open radical cystectomy for bladder cancer: perioperative and pathologic results. Eur Urol. 2010;57:196–201.PubMedCrossRefGoogle Scholar
  53. 53.
    Davis JW, Gaston K, Anderson R, Dinney CPN, Grossman HB, Munsell MF, et al. Robot assisted extended pelvic lymphadenectomy at radical cystectomy: lymph node yield compared with second look open dissection. J Urol. 2011;185:79–83.PubMedCrossRefGoogle Scholar
  54. 54.
    Parekh DJ, Messer J, Fitzgerald J, Ercole B, Svatek R. Perioperative outcomes and oncologic efficacy from a pilot prospective randomized clinical trial of open versus robotic assisted radical cystectomy. J Urol. 2013;189:474–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Davis JW, Kamat AM. Lymphadenectomy with robotic cystectomy. Curr Urol Rep. 2013;14:59–63.PubMedCrossRefGoogle Scholar
  56. 56.
    Lavery HJ, Martinez-Suarez HJ, Abaza R. Robotic extended pelvic lymphadenectomy for bladder cancer with increased nodal yield. BJU Int. 2011;107:1802–5.PubMedCrossRefGoogle Scholar
  57. 57.
    Tilki D, Brausi M, Colombo R, Evans CP, Fradet Y, Fritsche H-M, et al. Lymphadenectomy for bladder cancer at the time of radical cystectomy. Eur Urol. 2013;64:266–76.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Samuel D. Kaffenberger
    • 1
  • Todd M. Morgan
    • 2
    Email author
  • Anne K. Schuckman
    • 3
  1. 1.Department of Urologic SurgeryVanderbilt UniversityNashvilleUSA
  2. 2.Department of UrologyUniversity of MichiganAnn ArborUSA
  3. 3.USC Institute of UrologyKeck Medical Center of the University of Southern CaliforniaLos AngelesUSA

Personalised recommendations