title: Impact of tumour location versus multifocality in patients with upper tract urothelial carcinoma treated with nephroureterectomy and bladder cuff excision: a homogeneous series without perioperative chemotherapy.
abstract: It is well established that upper tract urothelial carcinoma is a rare cancer with an aggressive course. Currently, radical nephroureterectomy with bladder cuff excision remains the standard of care in the treatment of these tumours. Previous studies demonstrate that stage, grade and lymphovascular invasion have prognostic significance on recurrence and outcome whereas the prognostic impact of tumour location remains unclear. This study provides an accurate analysis of the impact of tumour location and multifocality on prognosis in patients with upper tract urothelial carcinoma following nephroureterectomy with bladder cuff excision. Ureteral tumour location, particularly when associated with multifocal disease in the renal pelvis, is significantly associated with an increased risk of disease recurrence and cancer-specific death after surgery.
  
  
  OBJECTIVE
  To examine the significance of ureteral and renal pelvic location of upper tract urothelial carcinoma in a large multi-institutional study.
  
  
  METHODS
  We collected and pooled a database of 637 patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy and bladder cuff excision in nine international academic centres. Univariate and multivariate models examined the effect of tumour location on recurrence-free survival (RFS) and cancer-specific survival (CSS) rates. Collected variables included age, gender, race, presence of lymphovascular invasion, concomitant carcinoma in situ, pathological stage, lymph node dissection and type of surgery (open vs laparoscopic).
  
  
  RESULTS
  Anatomically, 34% of tumours were ureteral, 59% were renal pelvic and 7% were multifocal. Median follow-up for patients alive was 42 months (interquartile range: 19-76). Race, type of surgery, pathological stage and presence of lymphovascular invasion were significantly different across the three subgroups of patients (all P values <0.05). Age, gender, grade, presence of concomitant carcinoma in situ and follow-up duration were similar among the three subgroups. On multivariable Cox regression analyses, ureteral tumour location was an independent predictor of worse RFS (hazard ratio 2.1, P = 0.006) and CSS (hazard ratio 2.0, P = 0.027). When associated with renal pelvic disease, ureteral location was an even stronger independent predictor of worse RFS (hazard ratio 4.6, P < 0.001) and CSS (hazard ratio 4.0, P < 0.001).
  
  
  CONCLUSIONS
  Ureteral tumour location, particularly in association with multifocal disease in the renal pelvis, is an independent prognostic factor for higher disease recurrence and cancer-specific mortality.
authors.affiliation: McGill University Health Center, Montreal, Quebec, Canada.
authors.forename: Faysal A
authors.initials: FA
authors.lastname: Yafi
authors.forename: Giacomo
authors.initials: G
authors.lastname: Novara
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.forename: Amit
authors.initials: A
authors.lastname: Gupta
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Walton
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Fritsche
authors.forename: Assaad
authors.initials: A
authors.lastname: El-Hakim
authors.forename: Stefan
authors.initials: S
authors.lastname: Trischler
authors.forename: Juan I
authors.initials: JI
authors.lastname: Martínez-Salamanca
authors.forename: Christian
authors.initials: C
authors.lastname: Seitz
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Ficarra
authors.forename: Filiberto
authors.initials: F
authors.lastname: Zattoni
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
authors.forename: Wassim
authors.initials: W
authors.lastname: Kassouf
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000401:mortality / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000209:etiology / Q000401:mortality; D009392:Nephrectomy / Q000379:methods* / Q000401:mortality; D011379:Prognosis; D012189:Retrospective Studies; D014513:Ureter / Q000601:surgery*; D014516:Ureteral Neoplasms / Q000401:mortality / Q000601:surgery*; D001743:Urinary Bladder / Q000601:surgery*; D019459:Urothelium