title: Prognostic significance of markers of systemic inflammatory response in patients with non-muscle-invasive bladder cancer.
abstract: The neutrophil-to-lymphocyte ratio (NLR) and the C-reactive protein (CRP) are markers of systemic inflammatory response, which have been associated with the prognosis of multiple malignancies, but their relationships with oncologic outcomes of non-muscle-invasive bladder cancer (NMIBC) have not been well studied yet.
  
  
  
  We retrospectively reviewed the medical records of 1,117 patients with NMIBC who underwent a transurethral resection of the bladder. Univariable and multivariable competing risk regression models were used to assess the association of preoperative NLR and CRP with disease recurrence and progression to muscle-invasive disease. The median follow-up was 64 months.
  
  
  
  In total, 360 patients (32.2%) had a high NLR (≥2.5) and 145 (13.0%) had a high CRP (≥5mg/l). On multivariable analyses, a high NLR was associated with both disease recurrence (subhazard ratio [SHR] = 1.27, P = 0.013) and progression (SHR = 1.72, P = 0.007), and high CRP was associated with disease progression (SHR = 1.72, P = 0.031). Adding NLR and CRP to the multivariable model predicting disease progression lead to a relevant change in discrimination (+2.0%). In a subgroup analysis of 300 patients treated with bacillus Calmette-Guerin, both high NLR and high CRP were associated with disease progression (SHR = 2.80, P = 0.026 and SHR = 3.51, P = 0.021, respectively), and NLR was associated with disease recurrence (SHR = 1.46, P = 0.046). There was also an increase in the discrimination of the model predicting progression after bacillus Calmette-Guerin following the inclusion of both markers (+2.4%).
  
  
  
  In patients with NMIBC, markers of systemic inflammation response are associated with disease recurrence and progression. The inclusion of such markers in prognostic models does enhance their accuracy.
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria; Department of Urology, University of Nice Sophia-Antipolis, Hôpital Archet 2, Centre Hospitalier Universitaire de Nice, Nice, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Mbeutcha
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria; Department of Urology, Weill Cornell Medical College, New York, NY; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX. Electronic address: sfshariat@gmail.com.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria; Department of Urology, University Hospital Basel, Basel, Switzerland.
authors.forename: Malte
authors.initials: M
authors.lastname: Rieken
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 Cochin Hospital, APHP, Paris Descartes University, Paris, France.
authors.forename: Evanguelos
authors.initials: E
authors.lastname: Xylinas
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Seitz
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna General Hospital, 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, Medical University of Vienna, Vienna General Hospital, Vienna, Austria; Department of Urology, Rennes University Hospital, Rennes, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Mathieu
authors.affiliation: Department of Urology, Pitié- Salpétrière, APHP, University Paris VI, Paris, France.
authors.forename: Morgan
authors.initials: M
authors.lastname: Rouprêt
authors.affiliation: Department of Urology, Università Vita-Salute, Ospedale S. Raffaele, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Briganti
authors.affiliation: Department of Urology, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors.forename: Tobias
authors.initials: T
authors.lastname: Klatte
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001500:BCG Vaccine / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D002295:Carcinoma, Transitional Cell / Q000097:blood* / Q000150:complications / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D015653:Cystectomy; D018450:Disease Progression; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000627:therapeutic use; D008954:Models, Biological; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009504:Neutrophils; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood* / Q000150:complications; D001749:Urinary Bladder Neoplasms / Q000097:blood* / Q000150:complications / Q000473:pathology / Q000628:therapy
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D001500:BCG Vaccine; D015415:Biomarkers; D016685:Mitomycin; D002097:C-Reactive Protein
keywords: BCG; Biomarker; Guideline; Prediction; Prognosis; Progression; Response