World Journal of Urology

, Volume 27, Issue 1, pp 27–32 | Cite as

The role of lymph node density in bladder cancer prognostication

Topic Paper


Pelvic lymph node metastases from bladder cancer occur in about 25% of patients undergoing radical cystectomy. While the majority of patients with lymph node metastases will develop progressive disease, some patients do exhibit long-term survival with and without adjuvant chemotherapy. The concept of lymph node density has been proposed as a means to stratify patient prognosis since it takes into account two important factors—the number of positive nodes (tumor burden) and the total number of nodes removed/examined (extent of dissection). Due to the lack of agreement on the extent of lymphadenectomy, lymph node density facilitates standardization of lymph node staging, thus allowing for adjuvant therapies and clinical trials to be more uniformly applied. Whether lymph node density provides improved prognostication over the standard nodal staging or absolute number of positive lymph nodes remains controversial. We review the literature regarding the role of lymph node density in the prognostic stratification of node-positive bladder cancer.


Lymph nodes Cystectomy Bladder neoplasms Lymphadenectomy 


  1. 1.
    Quek ML, Sanderson KM, Daneshmand S et al (2004) The importance of an extended lymphadenectomy in the management of high-grade invasive bladder cancer. Expert Rev Anticancer Ther 4:1007–1016. doi:10.1586/14737140.4.6.1007 PubMedCrossRefGoogle Scholar
  2. 2.
    Stein JP, Lieskovsky G, Cote R et al (2001) Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1, 054 patients. J Clin Oncol 19:666–675PubMedGoogle Scholar
  3. 3.
    Shariat SF, Karakiewicz PI, Palapattu GS et al (2006) Outcomes of radical cystectomy for transitional cell carcinoma of the bladder: a contemporary series from the Bladder Cancer Research Consortium. J Urol 176:2414–2422. doi:10.1016/j.juro.2006.08.004; discussion 2422PubMedCrossRefGoogle Scholar
  4. 4.
    Hautmann RE, Gschwend JE, de Petriconi RC et al (2006) Cystectomy for transitional cell carcinoma of the bladder: results of a surgery only series in the neobladder era. J Urol 176:486–492. doi:10.1016/j.juro.2006.03.038; discussion 491-2PubMedCrossRefGoogle Scholar
  5. 5.
    Skinner DG (1982) Management of invasive bladder cancer: a meticulous pelvic node dissection can make a difference. J Urol 128:34–36PubMedGoogle Scholar
  6. 6.
    Herr HW, Donat SM (2001) Outcome of patients with grossly node positive bladder cancer after pelvic lymph node dissection and radical cystectomy. J Urol 165:62–64. doi:10.1097/00005392-200101000-00015; discussion 64PubMedCrossRefGoogle Scholar
  7. 7.
    Vieweg J, Gschwend JE, Herr HW et al (1999) Pelvic lymph node dissection can be curative in patients with node positive bladder cancer. J Urol 161:449–454. doi:10.1016/S0022-5347(01)61921-9 PubMedCrossRefGoogle Scholar
  8. 8.
    Lerner SP, Skinner DG, Lieskovsky G et al (1993) The rationale for en bloc pelvic lymph node dissection for bladder cancer patients with nodal metastases: long-term results. J Urol 149:758–764 discussion 764-5PubMedGoogle Scholar
  9. 9.
    Mills RD, Turner WH, Fleischmann A et al (2001) Pelvic lymph node metastases from bladder cancer: outcome in 83 patients after radical cystectomy and pelvic lymphadenectomy. J Urol 166:19–23. doi:10.1016/S0022-5347(05)66067-3 PubMedCrossRefGoogle Scholar
  10. 10.
    Koppie TM, Vickers AJ, Vora K et al (2006) Standardization of pelvic lymphadenectomy performed at radical cystectomy: can we establish a minimum number of lymph nodes that should be removed? Cancer 107:2368–2374. doi:10.1002/cncr.22250 PubMedCrossRefGoogle Scholar
  11. 11.
    Konety BR, Joslyn SA, O’Donnell MA (2003) 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 169:946–950. doi:10.1097/01.ju.0000052721.61645.a3 PubMedCrossRefGoogle Scholar
  12. 12.
    Herr HW, Bochner BH, Dalbagni G et al (2002) Impact of the number of lymph nodes retrieved on outcome in patients with muscle invasive bladder cancer. J Urol 167:1295–1298. doi:10.1016/S0022-5347(05)65284-6 PubMedCrossRefGoogle Scholar
  13. 13.
    Vieweg J, Gschwend JE, Herr HW et al (1999) The impact of primary stage on survival in patients with lymph node positive bladder cancer. J Urol 161:72–76. doi:10.1016/S0022-5347(01)62067-6 PubMedCrossRefGoogle Scholar
  14. 14.
    Quek ML, Stein JP, Nichols PW et al (2005) Prognostic significance of lymphovascular invasion of bladder cancer treated with radical cystectomy. J Urol 174:103–106. doi:10.1097/01.ju.0000163267.93769.d8 PubMedCrossRefGoogle Scholar
  15. 15.
    Fleischmann A, Thalmann GN, Markwalder R et al (2005) Extracapsular extension of pelvic lymph node metastases from urothelial carcinoma of the bladder is an independent prognostic factor. J Clin Oncol 23:2358–2365. doi:10.1200/JCO.2005.03.084 PubMedCrossRefGoogle Scholar
  16. 16.
    Fleischmann A, Thalmann GN, Markwalder R et al (2005) Prognostic implications of extracapsular extension of pelvic lymph node metastases in urothelial carcinoma of the bladder. Am J Surg Pathol 29:89–95. doi:10.1097/01.pas.0000147396.08853.26 PubMedCrossRefGoogle Scholar
  17. 17.
    Stein JP, Cai J, Groshen S et al (2003) Risk factors for patients with pelvic lymph node metastases following radical cystectomy with en bloc pelvic lymphadenectomy: concept of lymph node density. J Urol 170:35–41. doi:10.1097/01.ju.0000072422.69286.0e PubMedCrossRefGoogle Scholar
  18. 18.
    Herr HW (2003) Superiority of ratio based lymph node staging for bladder cancer. J Urol 169:943–945. doi:10.1097/01.ju.0000032474.22093.06 PubMedCrossRefGoogle Scholar
  19. 19.
    Kassouf W, Agarwal PK, Herr HW et al (2008) 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 26:121–126. doi:10.1200/JCO.2007.12.9247 PubMedCrossRefGoogle Scholar
  20. 20.
    Stein JP (2006) Lymphadenectomy in bladder cancer: how high is “high enough”? Urol Oncol 24:349–355. doi:10.1016/j.urolonc.2005.07.013 PubMedGoogle Scholar
  21. 21.
    Dhar NB, Klein EA, Reuther AM et al (2008) Outcome after radical cystectomy with limited or extended pelvic lymph node dissection. J Urol 179:873–878. doi:10.1016/j.juro.2007.10.076; discussion 878PubMedCrossRefGoogle Scholar
  22. 22.
    Steven K, Poulsen AL (2007) Radical cystectomy and extended pelvic lymphadenectomy: survival of patients with lymph node metastasis above the bifurcation of the common iliac vessels treated with surgery only. J Urol 178:1218–1223. doi:10.1016/j.juro.2007.05.160; discussion 1223-4PubMedCrossRefGoogle Scholar
  23. 23.
    Kassouf W, Leibovici D, Munsell MF et al (2006) Evaluation of the relevance of lymph node density in a contemporary series of patients undergoing radical cystectomy. J Urol 176:53–57. doi:10.1016/S0022-5347(06)00510-6; discussion 57PubMedCrossRefGoogle Scholar
  24. 24.
    Abdel-Latif M, Abol-Enein H, El-Baz M et al (2004) Nodal involvement in bladder cancer cases treated with radical cystectomy: incidence and prognosis. J Urol 172:85–89. doi:10.1097/01.ju.0000132132.72351.4c PubMedCrossRefGoogle Scholar
  25. 25.
    Wright JL, Lin DW, Porter MP (2008) The association between extent of lymphadenectomy and survival among patients with lymph node metastases undergoing radical cystectomy. Cancer 112:2401–2408. doi:10.1002/cncr.23474 PubMedCrossRefGoogle Scholar
  26. 26.
    Gilbert SM (2008) Separating surgical quality from causality–gaining perspective in the debate on lymph node count and extent of lymphadenectomy. Cancer 112:2331–2333. doi:10.1002/cncr.23471 PubMedCrossRefGoogle Scholar
  27. 27.
    Farshid G, Pradhan M, Kollias J et al (2000) Computer simulations of lymph node metastasis for optimizing the pathologic examination of sentinel lymph nodes in patients with breast carcinoma. Cancer 89:2527–2537. doi:10.1002/1097-0142(20001215)89:12<2527::AID-CNCR3>3.0.CO;2-6PubMedCrossRefGoogle Scholar
  28. 28.
    Bochner BH, Herr HW, Reuter VE (2001) Impact of separate versus en bloc pelvic lymph node dissection on the number of lymph nodes retrieved in cystectomy specimens. J Urol 166:2295–2296. doi:10.1016/S0022-5347(05)65555-3 PubMedCrossRefGoogle Scholar
  29. 29.
    Herr HW (2007) The concept of lymph node density—is it ready for clinical practice? J Urol 177:1273–1275. doi:10.1016/j.juro.2006.11.094; discussion 1275-6PubMedCrossRefGoogle Scholar
  30. 30.
    Kamat AM, Fisher MB (2007) Lymph node density: surrogate marker for quality of resection in bladder cancer? Expert Rev Anticancer Ther 7:777–779. doi:10.1586/14737140.7.6.777 PubMedCrossRefGoogle Scholar
  31. 31.
    Skinner EC, Stein JP, Skinner DG (2007) Surgical benchmarks for the treatment of invasive bladder cancer. Urol Oncol 25:66–71. doi:10.1016/j.urolonc.2006.05.010 PubMedGoogle Scholar
  32. 32.
    Stein JP, Penson DF, Cai J et al (2007) Radical cystectomy with extended lymphadenectomy: evaluating separate package versus en bloc submission for node positive bladder cancer. J Urol 177:876–881. doi:10.1016/j.juro.2006.10.043; discussion 881-2PubMedCrossRefGoogle Scholar
  33. 33.
    Herr HW (2003) Surgical factors in bladder cancer: more (nodes) + more (pathology) = less (mortality). BJU Int 92:187–188. doi:10.1046/j.1464-410X.2003.04334.x PubMedCrossRefGoogle Scholar
  34. 34.
    Herr HW (2003) Extent of surgery and pathology evaluation has an impact on bladder cancer outcomes after radical cystectomy. Urology 61:105–108. doi:10.1016/S0090-4295(02)02116-7 PubMedCrossRefGoogle Scholar
  35. 35.
    Woods ME, Ouwenga M, Quek ML (2007) The role of pelvic lymphadenectomy in the management of prostate and bladder cancer. ScientificWorldJournal 7:789–799. doi:10.1100/tsw.2007.148 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Department of UrologyLoyola University Medical CenterMaywoodUSA

Personalised recommendations