title: Critical analysis of the 2010 TNM classification in patients with lymph node-positive bladder cancer: influence of lymph node disease burden.
abstract: OBJECTIVE
  In 2010, a new TNM staging system was published by American Joint Committee on Cancer, changing the nodal classification to include the presence of common iliac lymph node (LN) involvement as N3 category. The objective of this study was to define the capability of the current TNM nodal classification to separate patients with different prognostic stages and to evaluate the effect of LN disease burden.
  
  
  METHODS
  A total of 93 patients with metastatic LNs after radical cystectomy and extended LN dissection for urothelial carcinoma of the bladder between 1999 and 2012 were included. The median follow-up was 21.5 months. The correlation between N3 and indicators of LN disease burden was analyzed using the Spearman correlation coefficient. Recurrence-free survival (RFS) and overall survival (OS) analysis was performed using the Kaplan-Meier and Cox proportional hazards methods.
  
  
  RESULTS
  The presence of N3 disease was associated with higher number of metastatic LNs (7 vs. 2, P<0.01); however, this was highly variable and correlation coefficients between common iliac metastatic LNs and other lymphatic disease burden indicators demonstrated weak association (0.39-0.63). Patients with N1 lesions were found to have a distinct RFS and OS (P<0.01 and P = 0.01, respectively). A trend toward worse RFS (P = 0.07) and OS (P = 0.08) was observed in patients with N3 lesions. However, no difference in RFS or OS was found between patients with N2 and N3 lesions (P = 0.83 and 0.50, respectively).
  
  
  CONCLUSIONS
  The N3 category in the current TNM classification defines a group of patients with high but heterogeneous disease burden. This may be the explanation for its lack of prognostic stratification when compared with N2 category bladder cancer.
authors.affiliation: Department of Urology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Pedrosa
authors.affiliation: Department of Urology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Hristos Z
authors.initials: HZ
authors.lastname: Kaimakliotis
authors.affiliation: Department of Urology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: M Francesca
authors.initials: MF
authors.lastname: Monn
authors.affiliation: Department of Urology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: K Clint
authors.initials: KC
authors.lastname: Cary
authors.affiliation: Department of Urology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Masterson
authors.affiliation: Department of Urology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Rice
authors.affiliation: Department of Urology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Foster
authors.affiliation: Department of Urology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Richard
authors.initials: R
authors.lastname: Bihrle
authors.affiliation: Department of Urology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Koch
authors.affiliation: Department of Urology, Indiana University School of Medicine, Indianapolis, IN; Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN. Electronic address: liang_cheng@yahoo.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000145:classification / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods*; D011379:Prognosis; D016016:Proportional Hazards Models; D001749:Urinary Bladder Neoplasms / Q000145:classification / Q000401:mortality / Q000473:pathology*
keywords: Bladder; Cystectomy; Lymph node metastasis; Prognosis; TNM classifications; Urothelial carcinoma