title: Extranodal extension is a powerful prognostic factor in bladder cancer patients with lymph node metastasis.
abstract: BACKGROUND
  Lymph node metastasis (LNM) is the most powerful pathologic predictor of disease recurrence after radical cystectomy (RC). However, the outcomes of patients with LNM are highly variable.
  
  
  OBJECTIVE
  To assess the prognostic value of extranodal extension (ENE) and other lymph node (LN) parameters.
  
  
  METHODS
  A retrospective analysis of 748 patients with urothelial carcinoma of the bladder and LNM treated with RC and lymphadenectomy without neoadjuvant therapy at 10 European and North American centers (median follow-up: 27 mo).
  
  
  METHODS
  All subjects underwent RC and bilateral pelvic lymphadenectomy.
  
  
  METHODS
  Each LNM was microscopically evaluated for the presence of ENE. The number of LNs removed, number of positive LNs, and LN density were recorded and calculated. Univariable and multivariable analyses addressed time to disease recurrence and cancer-specific mortality after RC.
  
  
  CONCLUSIONS
  A total of 375 patients (50.1%) had ENE. The median number of LNs removed, number of positive LNs, and LN density were 15, 2, and 15, respectively. The rate of ENE increased with advancing pT stage (p<0.001). In multivariable Cox regression analyses that adjusted for the effects of established clinicopathologic features and LN parameters, ENE was associated with disease recurrence (hazard ratio [HR]: 1.89; 95% confidence interval [CI], 1.55-2.31; p<0.001) and cancer-specific mortality (HR: 1.90; 95% CI, 1.52-2.37; p<0.001). The addition of ENE to a multivariable model that included pT stage, tumor grade, age, gender, lymphovascular invasion, surgical margin status, LN density, number of LNs removed, number of positive LNs, and adjuvant chemotherapy improved predictive accuracy for disease recurrence and cancer-specific mortality from 70.3% to 77.8% (p<0.001) and from 71.8% to 77.8% (p=0.007), respectively. The main limitation of the study is its retrospective nature.
  
  
  CONCLUSIONS
  ENE is an independent predictor of both cancer recurrence and cancer-specific mortality in RC patients with LNM. Knowledge of ENE status could help with patient counseling, clinical decision making regarding inclusion in clinical trials of adjuvant therapy, and tailored follow-up scheduling after RC.
authors.affiliation: Department of Urology, Weill Cornell Medical College/New York-Presbyterian Hospital, New York, NY, USA; Department of Urology, General Hospital Sankt Poelten, Sankt Poelten, Austria.
authors.forename: Harun
authors.initials: H
authors.lastname: Fajkovic
authors.forename: Eugene K
authors.initials: EK
authors.lastname: Cha
authors.forename: Claudio
authors.initials: C
authors.lastname: Jeldres
authors.forename: Brian D
authors.initials: BD
authors.lastname: Robinson
authors.forename: Michael
authors.initials: M
authors.lastname: Rink
authors.forename: Evanguelos
authors.initials: E
authors.lastname: Xylinas
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Chromecki
authors.forename: Eckart
authors.initials: E
authors.lastname: Breinl
authors.forename: Robert S
authors.initials: RS
authors.lastname: Svatek
authors.forename: Gerhard
authors.initials: G
authors.lastname: Donner
authors.forename: Scott T
authors.initials: ST
authors.lastname: Tagawa
authors.forename: Derya
authors.initials: D
authors.lastname: Tilki
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Bastian
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
authors.forename: Bjoern G
authors.initials: BG
authors.lastname: Volkmer
authors.forename: Giacomo
authors.initials: G
authors.lastname: Novara
authors.forename: Abdennabi
authors.initials: A
authors.lastname: Joual
authors.forename: Talia
authors.initials: T
authors.lastname: Faison
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
authors.forename: Siamak
authors.initials: S
authors.lastname: Daneshmand
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Scherr
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D015653:Cystectomy / Q000009:adverse effects / Q000401:mortality; D005060:Europe; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008197:Lymph Node Excision / Q000009:adverse effects / Q000401:mortality; D008198:Lymph Nodes / Q000473:pathology* / Q000601:surgery*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009656:North America; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery*