title: Association of tumor necrosis with pathological features and clinical outcome in 754 patients undergoing radical nephroureterectomy for upper tract urothelial carcinoma: an international validation study.
abstract: OBJECTIVE
  Tumor necrosis is associated with a poor oncological outcome in patients with upper tract urothelial carcinoma and other malignancies. We validated the association of tumor necrosis with pathological features and clinical outcomes in a large international cohort of patients with upper tract urothelial carcinoma treated with radical nephroureterectomy.
  
  
  METHODS
  This retrospective study included 754 patients treated with radical nephroureterectomy at a total of 9 centers. Tumor necrosis was scored as greater than 10% of tumor area based on microscopic evaluation.
  
  
  RESULTS
  Tumor necrosis was present in 165 specimens (21.9%). The prevalence of tumor necrosis increased with advancing pathological stage, including 7%, 10.6% and 50% for T1, T2 and T3-4, respectively (p <0.001). Tumor necrosis was associated with features of aggressive upper tract urothelial carcinoma, such as high grade, lymph node metastasis, lymphovascular invasion, sessile tumor architecture and concomitant carcinoma in situ (p <0.002). Median followup in censored patients was 40 months (IQR 18 to 75). On univariate Cox regression analysis tumor necrosis was significantly associated with disease recurrence and cancer specific mortality (HR 2.4 and 2.7, p <0.001). However, on multivariate Cox regression analysis including patient age, stage, grade, lymph node status, lymphovascular invasion and adjuvant chemotherapy tumor necrosis was not associated with disease recurrence (HR 1.1, p = 0.49) or cancer specific mortality (HR 1.1, p = 0.51). Excluding 63 patients who received adjuvant chemotherapy and/or 49 with positive lymph nodes did not substantially change these results.
  
  
  CONCLUSIONS
  In this large, multicenter international study tumor necrosis was associated with pathological features of biologically aggressive upper tract urothelial carcinoma. However, tumor necrosis was not an independent predictor of clinical outcomes.
authors.affiliation: General Hospital Bolzano, Bolzano, Italy.
authors.forename: Christian
authors.initials: C
authors.lastname: Seitz
authors.forename: Amit
authors.initials: A
authors.lastname: Gupta
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Wassim
authors.initials: W
authors.lastname: Kassouf
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Walton
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Fritsche
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Otto
authors.forename: Stefan
authors.initials: S
authors.lastname: Tritschler
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Bastian
authors.forename: Joaquin
authors.initials: J
authors.lastname: Carballido
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Ficarra
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
authors.forename: Walter
authors.initials: W
authors.lastname: Artibani
authors.forename: Guido
authors.initials: G
authors.lastname: Mazzoleni
authors.forename: Giacomo
authors.initials: G
authors.lastname: Novara
mesh_terms: D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000473:pathology* / Q000601:surgery*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D009392:Nephrectomy; D012189:Retrospective Studies; D016896:Treatment Outcome; D014516:Ureteral Neoplasms / Q000473:pathology* / Q000601:surgery*