title: Promising role of preoperative neutrophil-to-lymphocyte ratio in patients treated with radical nephroureterectomy.
abstract: OBJECTIVE
  Several retrospective studies with small cohorts reported neutrophil-to-lymphocyte ratio (NLR) as a prognostic marker in upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU). We aimed at validating the predictive and prognostic role of NLR in a large multi-institutional cohort.
  
  
  METHODS
  Preoperative NLR was assessed in a multi-institutional cohort of 2477 patients with UTUC treated with RNU. Altered NLR was defined by a ratio >2.7. Logistic regression analyses were performed to assess the association between NLR and lymph node metastasis, muscle-invasive and non-organ-confined disease. The association of altered NLR with recurrence-free survival (RFS) and cancer-specific survival (CSS) was evaluated using Cox proportional hazards regression models.
  
  
  RESULTS
  Altered NLR was observed in 1428 (62.8 %) patients and associated with more advanced pathological tumor stage, lymph node metastasis, lymphovascular invasion, tumor necrosis and sessile tumor architecture. In a preoperative model that included age, gender, tumor location and architecture, NLR was an independent predictive factor for the presence of lymph node metastasis, muscle-invasive and non-organ-confined disease (p < 0.001). Within a median follow-up of 40 months (IQR 20-76 months), 548 (24.1 %) patients experienced disease recurrence and 453 patients (19.9 %) died from their cancer. Compared to patients with normal NLR, those with altered NLR had worse RFS (0.003) and CSS (p = 0.002). In multivariable analyses that adjusted for the effects of standard clinicopathologic features, altered NLR did not retain an independent value. In the subgroup of patients treated with lymphadenectomy in addition to RNU, NLR was independently associated with CSS (p = 0.03).
  
  
  CONCLUSIONS
  In UTUC, preoperative NLR is associated with adverse clinicopathologic features and independently predicts features of biologically and clinically aggressive UTUC such as lymph node metastasis, muscle-invasive or non-organ-confined status. NLR may help better risk stratify patients with regard to lymphadenectomy and conservative therapy.
authors.affiliation: Department of Urology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.|Department of Cell and Molecular Biology, University of Medicine and Pharmacy, Targu Mures, Romania.
authors.forename: Mihai Dorin
authors.initials: MD
authors.lastname: Vartolomei
authors.affiliation: Department of Urology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.|Department of Urology, Rennes University Hospital, Rennes, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Mathieu
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Margulis
authors.affiliation: Department of Urology, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Karam
authors.affiliation: Academic Department of Urology, La Pitié-Salpetrière Hospital, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Pierre et Marie Curie, University Paris 6, Paris, France.
authors.forename: Morgan
authors.initials: M
authors.lastname: Rouprêt
authors.affiliation: Department of Urology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.|Department of Urology, Centre hospitalier universitaire vaudois, Lausanne, Switzerland.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lucca
authors.affiliation: Department of Urology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Mbeutcha
authors.affiliation: Department of Urology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Seitz
authors.affiliation: Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Canada.
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
authors.affiliation: Department of Urology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.
authors.forename: Harun
authors.initials: H
authors.lastname: Fajkovic
authors.affiliation: Department of Urology, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Wood
authors.affiliation: Department of Urology, University of Michigan Cancer Center, Ann Arbor, MI, USA.
authors.forename: Alon Z
authors.initials: AZ
authors.lastname: Weizer
authors.affiliation: Division of Urology, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA.
authors.forename: Jay D
authors.initials: JD
authors.lastname: Raman
authors.affiliation: Department of Pathology, Rennes University Hospital, Rennes, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rioux-Leclercq
authors.affiliation: Department of Pathology, Medical University of Vienna, Vienna, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Haitel
authors.affiliation: Department of Urology, Rennes University Hospital, Rennes, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Bensalah
authors.affiliation: Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Rink
authors.affiliation: Department of Urology, Vita Salute San Raffaele University, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Briganti
authors.affiliation: Department of Urology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris Descartes University, Paris, France.
authors.forename: Evanguelos
authors.initials: E
authors.lastname: Xylinas
authors.affiliation: Department of Urology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria. shahrokh.shariat@meduniwien.ac.at.|Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA. shahrokh.shariat@meduniwien.ac.at.|Department of Urology, Weill Cornell Medical College, New York, NY, USA. shahrokh.shariat@meduniwien.ac.at.|Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. shahrokh.shariat@meduniwien.ac.at.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
mesh_terms: D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D007958:Leukocyte Count; D018655:Lymphocyte Count; D008214:Lymphocytes; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009392:Nephrectomy; D009504:Neutrophils; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D047368:Tumor Burden; D014513:Ureter / Q000601:surgery*; D014516:Ureteral Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000601:surgery
keywords: Carcinoma; Death; Neutrophil-to-lymphocyte ratio; Prognostic factor; Recurrence; Urothelium