title: Critical analysis and validation of lymph node density as prognostic variable in urothelial carcinoma of bladder.
abstract: OBJECTIVE
  To validate the prognostic relevance of lymph node density (LND) and identify its optimal cut-points in a large international multicenter series of patients treated with radical cystectomy (RC) for invasive bladder cancer.
  
  
  METHODS
  From 1993 to 2005, 4,430 bladder cancer patients who underwent RC without neoadjuvant chemotherapy were reviewed; of these, 1,038 were pN+M0 disease and form the basis of this report.
  
  
  RESULTS
  Median age of patients was 67 years with median follow-up in survivors of 33 months. Overall, 5-year DSS estimate was 36%. Median number of lymph nodes removed was 18 (IQR, 11-32), median number of positive lymph nodes was 2 (IQR, 1-5), and median LND was 14.3% (IQR, 6.67-33.3%). LND as continuous variable was a stronger prognostic factor for DSS in patients that underwent a more extensive PLND (P < 0.001). HR for inverse association of LND with DSS increased incrementally with increasing LND cut-points. Categorizing LND into quintiles revealed strong tertiary distribution of risk based on LND <6%, 6%-41%, or >41% with cumulative 5-year DSS of 47%, 36%, and 21%, respectively (P < 0.001). When patients were stratified by adjuvant chemotherapy, LND remains independently prognostic in patients who received adjuvant chemotherapy as well as those who did not.
  
  
  CONCLUSIONS
  Lymph node density is prognostic in bladder cancer patients who undergo a more extensive PLND and remains prognostic even when adjuvant chemotherapy is used. Prognostic value of LND is best represented as a continuum of risk and LND <6% represents the best possible outcome in patients with nodal disease.
authors.affiliation: McGill University Health Centre, Montréal, Quebec, Canada. wassim.kassouf@muhc.mcgill.ca
authors.forename: Wassim
authors.initials: W
authors.lastname: Kassouf
authors.forename: Robert S
authors.initials: RS
authors.lastname: Svatek
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.forename: Giacomo
authors.initials: G
authors.lastname: Novara
authors.forename: Seth P
authors.initials: SP
authors.lastname: Lerner
authors.forename: Yves
authors.initials: Y
authors.lastname: Fradet
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Bastian
authors.forename: Armen
authors.initials: A
authors.lastname: Aprikian
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
authors.forename: Hans Martin
authors.initials: HM
authors.lastname: Fritsche
authors.forename: Colin P N
authors.initials: CP
authors.lastname: Dinney
authors.forename: Derya
authors.initials: D
authors.lastname: Tilki
authors.forename: Ashish M
authors.initials: AM
authors.lastname: Kamat
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Izawa
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Ficarra
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.forename: Arthur I
authors.initials: AI
authors.lastname: Sagalowsky
authors.forename: Mark P
authors.initials: MP
authors.lastname: Schoenberg
authors.forename: Eila C
authors.initials: EC
authors.lastname: Skinner
mesh_terms: D000368:Aged; D002278:Carcinoma in Situ / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D003558:Cystoscopy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007390:International Agencies; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery