title: Tumour necrosis is an indicator of aggressive biology in patients with urothelial carcinoma of the upper urinary tract.
abstract: BACKGROUND
  Prognostic factors after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) are inconclusive, because most data in the literature have been obtained from small series.
  
  
  OBJECTIVE
  To assess the association of tumour necrosis with cancer recurrence and survival in a large international series of patients treated with RNU.
  
  
  METHODS
  Data were collected from 1425 patients treated with RNU at 13 centres and combined into a relational database. Pathologic slides were re-reviewed by genitourinary pathologists according to strict criteria. Extensive tumour necrosis was scored as >10% of the tumour area.
  
  
  METHODS
  Patients underwent either open or laparoscopic RNU. Lymph node dissection was performed in the presence of enlarged nodes.
  
  
  METHODS
  Recurrence was defined as tumour relapse in the operative field, lymph node (LN) metastasis, and/or distant metastases. Bladder recurrences were not considered. Associations of extensive tumour necrosis with recurrence-free survival and cancer-specific survival were evaluated by univariate and multivariate analyses.
  
  
  CONCLUSIONS
  Extensive tumour necrosis was observed in 364 patients (25.5%) and was associated with advanced tumour stage, high tumour grade, sessile architecture, lymphovascular invasion (LVI), concomitant carcinoma in situ, and LN metastasis (p<0.0001 each). Extensive tumour necrosis was independently associated with disease recurrence and survival (p=0.037 and p=0.046, respectively) after adjusting for the effects of pathologic stage, grade, LVI, and LN status. The addition of extensive tumour necrosis to a base model comprising standard pathologic predictors marginally improved its predictive accuracy for both cancer-specific recurrence (1.5%) and survival (1.4%).
  
  
  CONCLUSIONS
  Extensive tumour necrosis is an independent predictor of clinical outcomes in patients who undergo RNU for UTUC. Assessment of tumour necrosis may help to identify patients who could benefit from multimodal therapy after RNU in the future. Evaluation of extensive tumour necrosis should be part of standard pathologic reporting.
authors: Medical University of Graz, Graz, Austria.
authors: Richard
authors: R
authors: Zigeuner
authors: Shahrokh F
authors: SF
authors: Shariat
authors: Vitaly
authors: V
authors: Margulis
authors: Pierre I
authors: PI
authors: Karakiewicz
authors: Marco
authors: M
authors: Roscigno
authors: Alon
authors: A
authors: Weizer
authors: Eiji
authors: E
authors: Kikuchi
authors: Mesut
authors: M
authors: Remzi
authors: Jay D
authors: JD
authors: Raman
authors: Christian
authors: C
authors: Bolenz
authors: Karim
authors: K
authors: Bensalah
authors: Umberto
authors: U
authors: Capitanio
authors: Theresa M
authors: TM
authors: Koppie
authors: Wassim
authors: W
authors: Kassouf
authors: Kanishka
authors: K
authors: Sircar
authors: Jean-Jacques
authors: JJ
authors: Patard
authors: Mario I
authors: MI
authors: Fernández
authors: Christopher G
authors: CG
authors: Wood
authors: Francesco
authors: F
authors: Montorsi
authors: Philipp
authors: P
authors: Ströbel
authors: Jeffery C
authors: JC
authors: Wheat
authors: Andrea
authors: A
authors: Haitel
authors: Mototsugu
authors: M
authors: Oya
authors: Charles C
authors: CC
authors: Guo
authors: Casey
authors: C
authors: Ng
authors: Daher C
authors: DC
authors: Chade
authors: Arthur
authors: A
authors: Sagalowsky
authors: Cord
authors: C
authors: Langner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002677:Chile; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D007682:Kidney Pelvis / Q000473:pathology* / Q000601:surgery; D010535:Laparoscopy; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009392:Nephrectomy / Q000379:methods; D009656:North America; D018579:Patient Selection; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014513:Ureter / Q000473:pathology* / Q000601:surgery; D014516:Ureteral Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D019459:Urothelium / Q000473:pathology