title: Neutrophil-to-lymphocyte ratio is a prognostic marker in bladder cancer patients after radical cystectomy.
abstract: BACKGROUND
  There is no reliable biomarker for predicting the prognosis of patients who undergo radical cystectomy for bladder cancer. Recent studies have shown that the neutrophil-to-lymphocyte ratio (NLR) could function as a useful prognostic factor in several types of malignancies. This study aimed to assess the usefulness of NLR in bladder cancer.
  
  
  METHODS
  A total of 74 patients who underwent radical cystectomy in our institutions from 1999 to 2014 were analyzed. The NLR was calculated using the patients' neutrophil and lymphocyte counts before radical cystectomy. An immunohistochemical analysis was also performed to detect tumor infiltrating neutrophils (CD66b) and lymphocytes (CD8) in bladder cancer specimens.
  
  
  RESULTS
  A univariate analysis showed that the patients with a high NLR (≥2.38; HR = 4.84; p = 0.007), high C-reactive protein level (>0.08; HR = 10.06; p = 0.030), or pathological lymph node metastasis (HR = 4.73; p = 0.030) had a significantly higher risk of cancer-specific mortality. Kaplan-Meier and log-rank tests further revealed that NLR was strongly correlated with overall survival (p = 0.018), but not progression-free survival (p = 0.137). In a multivariate analysis, all of these were found to be independent risk factors (HR = 4.62, 10.8, and 12.35, respectively). The number of CD8-positive lymphocytes was significantly increased in high-grade (p = 0.001) and muscle-invasive (p = 0.012) tumors, in comparison to low-grade and non-muscle-invasive tumors, respectively.
  
  
  CONCLUSIONS
  The NLR predicted the prognosis of patients who underwent radical cystectomy and might therefore function as a reliable biomarker in cases of invasive bladder cancer.
authors.affiliation: Department of Urology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. takashi_tk2001@yahoo.co.jp.|Departments of Urology and Renal Transportation, Yokohama City University Medical Center, Yokohama, Japan. takashi_tk2001@yahoo.co.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawahara
authors.affiliation: Department of Urology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. kazuhiro.furuya1981@gmail.com.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Furuya
authors.affiliation: Departments of Urology and Renal Transportation, Yokohama City University Medical Center, Yokohama, Japan. hirojiuemura@icloud.com.
authors.forename: Manami
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Biostatistics, Yokohama City University Graduate School of Medicine, Yokohama, Japan. sakamaki@yokohama-cu.ac.jp.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Sakamaki
authors.affiliation: Department of Urology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. ousaka@yokohama-cu.ac.jp.
authors.forename: Kimito
authors.initials: K
authors.lastname: Osaka
authors.affiliation: Department of Urology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. pug_daikichi@yahoo.co.jp.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ito
authors.affiliation: Department of Urology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. yusukeitou1@gmail.com.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Urology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. koji.izumi522@gmail.com.
authors.forename: Koji
authors.initials: K
authors.lastname: Izumi
authors.affiliation: Department of Urology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. sohtake1112@live.jp.
authors.forename: Shinji
authors.initials: S
authors.lastname: Ohtake
authors.affiliation: Departments of Urology and Renal Transportation, Yokohama City University Medical Center, Yokohama, Japan. miyoyasu@yokohama-cu.ac.jp.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Miyoshi
authors.affiliation: Department of Urology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. makiya@yokohama-cu.ac.jp.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Makiyama
authors.affiliation: Department of Urology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. nakaigan@yokohama-cu.ac.jp.
authors.forename: Noboru
authors.initials: N
authors.lastname: Nakaigawa
authors.affiliation: Department of Biostatistics, Yokohama City University Graduate School of Medicine, Yokohama, Japan. yamanaka@yokohama-cu.ac.jp.
authors.forename: Takeharu
authors.initials: T
authors.lastname: Yamanaka
authors.affiliation: Departments of Pathology and Urology, Johns Hopkins University School of Medicine, Baltimore, USA. hmiyamo1@jhmi.edu.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyamoto
authors.affiliation: Department of Urology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. masayao@yokohama-cu.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yao
authors.affiliation: Department of Urology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. hu0428@yokohama-cu.ac.jp.|Departments of Urology and Renal Transportation, Yokohama City University Medical Center, Yokohama, Japan. hu0428@yokohama-cu.ac.jp.
authors.forename: Hiroji
authors.initials: H
authors.lastname: Uemura
mesh_terms: D000368:Aged; D015415:Biomarkers; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D015653:Cystectomy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007958:Leukocyte Count; D018655:Lymphocyte Count; D008214:Lymphocytes; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009504:Neutrophils; D063868:Patient Outcome Assessment; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy
chemical_list: D015415:Biomarkers