title: Pre-treatment neutrophil-to-lymphocyte ratio as predictor of adverse outcomes in patients undergoing radical cystectomy for urothelial carcinoma of the bladder.
abstract: BACKGROUND
  An elevated neutrophil-to-lymphocyte ratio (NLR) is associated with poor outcome in various tumours. Its prognostic utility in patients with urothelial carcinoma of the bladder (UCB) undergoing radical cystectomy (RC) is yet to be fully elucidated.
  
  
  METHODS
  A cohort of patients undergoing RC for UCB in a tertiary referral centre between 1992 and 2012 was analysed. Neutrophil-to-lymphocyte ratio was computed using complete blood counts performed pre-RC, or before neo-adjuvant chemotherapy where applicable. Time-dependent receiver operating characteristic curves were used to determine the optimal cutoff point for predicting recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). The predictive ability of NLR was assessed using Kaplan-Meier analyses and multivariable Cox proportional hazards models. The likelihood-ratio test was used to determine whether multivariable models were improved by including NLR.
  
  
  RESULTS
  The cohort included 424 patients followed for a median of 58.4 months. An NLR of 3 was determined as the optimal cutoff value. Patients with an NLR⩾3.0 had significantly worse survival outcomes (5y-RFS: 53% vs 64%, log-rank P=0.013; 5y-CSS: 57% vs 75%, log-rank P<0.001; 5y-OS: 43% vs 64%, log-rank P<0.001). After adjusting for disease-specific predictors, an NLR ⩾3.0 was significantly associated with worse RFS (HR=1.49; 95% CI=1.12-2.0, P=0.007), CSS (HR=1.88; 95% CI=1.39-2.54, P<0.001) and OS (average HR=1.67; 95% CI=1.17-2.39, P=0.005). The likelihood-ratio test confirmed that prognostic models were improved by including NLR.
  
  
  CONCLUSIONS
  Neutrophil-to-lymphocyte ratio is an inexpensive prognostic biomarker for patients undergoing RC for UCB. It offers pre-treatment prognostic value in addition to established prognosticators and may be helpful in guiding treatment decisions.
authors.affiliation: 1] Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9 [2] Division of Urology, Department of Surgery, University Health Network, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
authors.forename: T
authors.initials: T
authors.lastname: Hermanns
authors.affiliation: 1] Division of Urology, Department of Surgery, University Health Network, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9 [2] Institute for Clinical Evaluative Sciences, 2075 Bayview Avenue, Toronto, Ontario, Canada M4N 3M5.
authors.forename: B
authors.initials: B
authors.lastname: Bhindi
authors.affiliation: Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
authors.forename: Y
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.affiliation: 1] Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9 [2] Division of Urology, Department of Surgery, University Health Network, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
authors.forename: A P
authors.initials: AP
authors.lastname: Noon
authors.affiliation: 1] Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9 [2] Division of Urology, Department of Surgery, University Health Network, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
authors.forename: P O
authors.initials: PO
authors.lastname: Richard
authors.affiliation: 1] Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9 [2] Division of Urology, Department of Surgery, University Health Network, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
authors.forename: J R
authors.initials: JR
authors.lastname: Bhatt
authors.affiliation: 1] Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9 [2] Division of Urology, Department of Surgery, University Health Network, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
authors.forename: A
authors.initials: A
authors.lastname: Almatar
authors.affiliation: 1] Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9 [2] Division of Urology, Department of Surgery, University Health Network, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
authors.forename: M A S
authors.initials: MA
authors.lastname: Jewett
authors.affiliation: 1] Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9 [2] Division of Urology, Department of Surgery, University Health Network, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
authors.forename: N E
authors.initials: NE
authors.lastname: Fleshner
authors.affiliation: 1] Division of Urology, Department of Surgery, University Health Network, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9 [2] Department of Urology, Mount Sinai Hospital, 60 Murray Street, Toronto, Ontario, Canada M5T 3L9.
authors.forename: A R
authors.initials: AR
authors.lastname: Zlotta
authors.affiliation: Division of Medical Oncology, Department of Medicine, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
authors.forename: A J
authors.initials: AJ
authors.lastname: Templeton
authors.affiliation: 1] Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9 [2] Division of Urology, Department of Surgery, University Health Network, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9 [3] Institute for Clinical Evaluative Sciences, 2075 Bayview Avenue, Toronto, Ontario, Canada M4N 3M5.
authors.forename: G S
authors.initials: GS
authors.lastname: Kulkarni
mesh_terms: D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000276:immunology* / Q000401:mortality / Q000601:surgery; D015653:Cystectomy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology*; D057234:Preoperative Period; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D012189:Retrospective Studies; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000401:mortality / Q000601:surgery