title: Risk stratification of patients with nodal involvement in upper tract urothelial carcinoma: value of lymph-node density.
abstract: OBJECTIVE
  To determine the risk factors associated with clinical outcome in patients with lymph node (LN)-positive urothelial carcinoma of the upper urinary tract (UTUC) treated with radical nephroureterectomy (RNU) and lymphadenectomy, focusing on the concept of LN density (LND).
  
  
  METHODS
  Patients undergoing RNU with regional lymphadenectomy were identified through multi-institutional databases. All pathology slides were re-evaluated by genitourinary pathologists unaware of the clinical data. The exposure variable used was LND (continuously coded and that of all possible thresholds) with recurrence-free and disease-specific survival (DSS) serving as the outcome measures.
  
  
  RESULTS
  Of 432 patients undergoing RNU with lymphadenectomy, 135 (31%) had LN metastases. Within a median follow-up of 4.1 years, 90 of the 135 patients with LN metastases (68%) had disease recurrence and 76 (58%) died from UTUC. The mean (sem) 5-year recurrence-free and DSS probabilities were 27 (4)% and 33 (5)%, respectively. The median (range) LND was 50 (3-100)%. The most informative threshold for LND in relation to outcome was 30%. In multivariable analyses that adjusted for the effects of tumour stage and grade, patients with a LND of > or =30% were at greater risk of both cancer recurrence, with 5-year rates of 25 (5)% vs 38 (8)% (hazard ratio 1.8, P = 0.021) and mortality, with 5-year rates of 30 (6)% vs 48 (9)% (1.7, P = 0.032) compared to those with a LND of <30%. Our results are primarily limited by a lack of standardization in the lymphadenectomy template.
  
  
  CONCLUSIONS
  We evaluated the concept of LND for the first time in UTUC. LND provides additional prognostic information in patients with node-positive disease after RNU. The use of LND in clinical trials might provide an additional insight into the value of LN dissection in patients undergoing RNU.
authors.affiliation: Mannheim Medical Center, University of Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Bolenz
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.forename: Mario I
authors.initials: MI
authors.lastname: Fernández
authors.forename: Vitaly
authors.initials: V
authors.lastname: Margulis
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.forename: Pierre
authors.initials: P
authors.lastname: Karakiewicz
authors.forename: Mesut
authors.initials: M
authors.lastname: Remzi
authors.forename: Eiji
authors.initials: E
authors.lastname: Kikuchi
authors.forename: Richard
authors.initials: R
authors.lastname: Zigeuner
authors.forename: Alon
authors.initials: A
authors.lastname: Weizer
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.forename: Karim
authors.initials: K
authors.lastname: Bensalah
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Wood
authors.forename: Marco
authors.initials: M
authors.lastname: Roscigno
authors.forename: Cord
authors.initials: C
authors.lastname: Langner
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Koppie
authors.forename: Jay D
authors.initials: JD
authors.lastname: Raman
authors.forename: Shuji
authors.initials: S
authors.lastname: Mikami
authors.forename: Maurice Stephan
authors.initials: MS
authors.lastname: Michel
authors.forename: Philipp
authors.initials: P
authors.lastname: Ströbel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D008197:Lymph Node Excision / Q000379:methods*; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009392:Nephrectomy / Q000379:methods*; D011379:Prognosis; D012307:Risk Factors; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000473:pathology* / Q000601:surgery