title: Neutrophil-to-lymphocyte ratio as a bladder cancer biomarker: Assessing prognostic and predictive value in SWOG 8710.
abstract: BACKGROUND
  Risk stratification is a major challenge in bladder cancer (BC), and a biomarker is needed. Multiple studies have reported the neutrophil-to-lymphocyte ratio (NLR) as a promising candidate; however, these analyses have methodological limitations. Therefore, the authors performed a category B biomarker study to test whether NLR is prognostic for overall survival (OS) after curative treatment or is predictive for the survival benefit from neoadjuvant chemotherapy (NAC).
  
  
  METHODS
  This study is an unplanned secondary analysis of SWOG 8710, a randomized phase 3 trial that assessed cystectomy with or without NAC in 317 patients with muscle-invasive BC. NLR was calculated from prospectively collected complete blood counts. For the prognostic analysis, 230 patients were identified; for the predictive analysis, 263 were identified. NLR was evaluated with proportional hazards models including prespecified factors (age, sex, T-stage, lymphovascular invasion, and treatment arm).
  
  
  RESULTS
  With a median follow-up of 18.6 years, there were 172 and 205 deaths in the prognostic and predictive cohorts, respectively. In a multivariable analysis, NLR was not prognostic for OS (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.98-1.11; P = .24). Furthermore, NLR did not predict for the OS benefit from NAC (HR, 1.01; 95% CI, 0.90-1.14; P = .86). Factors associated with worse OS were older age (HR, 1.05; 95% CI, 1.04-1.07; P < .001) and surgery without NAC (HR, 1.39; 95% CI, 1.03-1.88; P = .03).
  
  
  CONCLUSIONS
  This is the first analysis of NLR in BC to use prospectively collected clinical trial data. In contrast to previous studies, it suggests that NLR is neither a prognostic nor predictive biomarker for OS in muscle-invasive BC. Cancer 2017;123:794-801. © 2016 American Cancer Society.
authors: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Eric
authors: http://orcid.org/0000-0002-1653-9559
authors: E
authors: Ojerholm
authors: Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Andrew
authors: A
authors: Smith
authors: Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Wei-Ting
authors: WT
authors: Hwang
authors: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Brian C
authors: BC
authors: Baumann
authors: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Kai N
authors: KN
authors: Tucker
authors: Urology, Baylor College of Medicine, Houston, Texas.
authors: Seth P
authors: SP
authors: Lerner
authors: Medical Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Ronac
authors: R
authors: Mamtani
authors: Medical Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Ben
authors: B
authors: Boursi
authors: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: John P
authors: JP
authors: Christodouleas
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001772:Blood Cell Count; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009504:Neutrophils / Q000473:pathology; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor
keywords: biomarker; bladder cancer; neutrophil-to-lymphocyte ratio (NLR)