title: The impact of tumor multifocality on outcomes in patients treated with radical nephroureterectomy.
abstract: BACKGROUND
  The prognostic impact of multifocal upper-tract urothelial carcinoma (UTUC) is poorly understood.
  
  
  OBJECTIVE
  To investigate the association between tumor multifocality and clinicopathologic features and outcomes of UTUC in patients managed by radical nephroureterectomy (RNU).
  
  
  METHODS
  The study included 2492 patients treated with either open or laparoscopic RNU. Tumor and patient characteristics included tumor stage, tumor grade, lymph node status, lymphovascular invasion (LVI), tumor architecture, tumor location, unifocal or multifocal disease, gender, age, history of bladder cancer (BCa), Eastern Cooperative Oncology Group (ECOG) performance status (PS), and adjuvant chemotherapy. tumor multifocality of UTUC was defined as the synchronous presence of multiple tumors in the renal pelvis or ureter.
  
  
  METHODS
  All patients were treated with either open or laparoscopic RNU.
  
  
  METHODS
  Univariable and multivariable models tested the effect of tumor multifocality on disease progression and cancer-specific mortality.
  
  
  CONCLUSIONS
  Five hundred ninety patients (23.7%) had tumor multifocality at the time of RNU. The median follow-up was 45 mo (interquartile range [IQR]: 0-101). Tumor multifocality was significantly associated with a history of previous BCa (p=0.032), lymph node involvement (p=0.036), tumor location in the ureter (p=0.003), higher tumor stage (p<0.001), higher tumor grade (p<0.001), sessile tumor architecture (p=0.003), and LVI (p=0.001). In organ-confined patients, tumor multifocality was an independent predictor of both disease progression (hazard ratio [HR]: 1.43; p=0.019) and cancer-specific mortality (HR: 1.46; p=0.027). When assessed in all patients, tumor multifocality was associated with both disease progression and cancer-specific mortality in univariable (p=0.005 and p=0.006, respectively) but not in multivariable analyses (p=0.468 and p=0.798, respectively). The main limitation is the retrospective design of the study.
  
  
  CONCLUSIONS
  Tumor multifocality is an independent prognosticator of disease progression and cancer-specific mortality in patients with organ-confined UTUC treated with RNU. Multifocal organ-confined patients with UTUC may need closer follow-up. Integration of tumor multifocality with other factors may help identify those patients who would benefit from multimodal therapy.
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY 10065, USA.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Chromecki
authors.forename: Eugene K
authors.initials: EK
authors.lastname: Cha
authors.forename: Harun
authors.initials: H
authors.lastname: Fajkovic
authors.forename: Vitaly
authors.initials: V
authors.lastname: Margulis
authors.forename: Giacomo
authors.initials: G
authors.lastname: Novara
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Scherr
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.forename: Jay D
authors.initials: JD
authors.lastname: Raman
authors.forename: Wassim
authors.initials: W
authors.lastname: Kassouf
authors.forename: Karim
authors.initials: K
authors.lastname: Bensalah
authors.forename: Alon
authors.initials: A
authors.lastname: Weizer
authors.forename: Eiji
authors.initials: E
authors.lastname: Kikuchi
authors.forename: Marco
authors.initials: M
authors.lastname: Roscigno
authors.forename: Mesut
authors.initials: M
authors.lastname: Remzi
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Walton
authors.forename: Armin
authors.initials: A
authors.lastname: Pycha
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Ficarra
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
authors.forename: Richard
authors.initials: R
authors.lastname: Zigeuner
authors.forename: Karl
authors.initials: K
authors.lastname: Pummer
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000401:mortality / Q000601:surgery*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000401:mortality / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000601:surgery; D009392:Nephrectomy / Q000379:methods*; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D014513:Ureter / Q000601:surgery*; D014516:Ureteral Neoplasms / Q000401:mortality / Q000601:surgery*