title: Prognostic impact of the neutrophil-to-lymphocyte ratio in men with metastatic castration-resistant prostate cancer.
abstract: BACKGROUND
  We retrospectively evaluated the prognostic impact of neutrophil-lymphocyte ratio (NLR) as a marker for inflammatory and immune state in men with progressive metastatic castration resistant prostate cancer (mCRPC) following docetaxel.
  
  
  METHODS
  The SUN-1120 phase III trial comparing prednisone combined with sunitinib (n = 584) or placebo (n = 289) for mCRPC following docetaxel-based chemotherapy was evaluated. The arms were combined for analysis, since no difference was observed in the primary endpoint of overall survival (OS). A logarithmic transformation was applied to non-normal factors. The Kaplan-Meier method was used for OS estimation. To identify an optimal prognostic model for survival, we used a Cox proportional hazards regression method with forward stepwise selection, stratifying for ECOG PS, progression type (prostate specific antigen [PSA] or radiographic) and treatment group. Patients were categorized into risk groups.
  
  
  RESULTS
  Complete data was evaluable for 784 men. The factors used in the model that remained individually significant for OS in multivariable analysis were: log-lactate dehydrogenase level (LDH) level (HR 2.86 [95% CI = 2.29, 3.56], P < .001), hemoglobin (0.80 [0.74, 0.85], P < .001), > 1 organ involved by metastatic disease (1.49 [1.21, 1.84], P < .001), log-alkaline phosphatase (1.13 [0.99, 1.28], P = .074), log-number of prior cycles of docetaxel (0.84 [0.71, 0.98], P = .031), progression on docetaxel (1.35 [1.00, 1.81], P = .049), log-PSA (1.06 [1.00, 1.12], P = .075) and log-NLR (1.55 [1.32, 1.83], P < .001). NLR increased the c-statistic of the prognostic model from 0.703 to 0.715.
  
  
  CONCLUSIONS
  High NLR may be associated with an independent poor prognostic impact in post-docetaxel patients with mCRPC. These data warrant external validation.
authors.affiliation: University of Alabama, Birmingham (UAB) Comprehensive Cancer Center, Birmingham, AL. Electronic address: gsonpavde@uabmc.edu.
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
authors.affiliation: Ontario Clinical Oncology Group, McMaster University, Hamilton, Canada.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Pond
authors.affiliation: Duke University, Durham, NC.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Armstrong
authors.affiliation: University of Sydney, Sydney, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Clarke
authors.affiliation: University of Sydney, Sydney, Australia.
authors.forename: Janette L
authors.initials: JL
authors.lastname: Vardy
authors.affiliation: Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Arnoud J
authors.initials: AJ
authors.lastname: Templeton
authors.affiliation: Pfizer Inc, New Jersey, NJ; ICON Clinical Research Inc, San Diego, CA.
authors.forename: Shaw-Ling
authors.initials: SL
authors.lastname: Wang
authors.affiliation: Pfizer Inc, New Jersey, NJ.
authors.forename: Jolanda
authors.initials: J
authors.lastname: Paolini
authors.affiliation: Pfizer Inc, New Jersey, NJ; Aragon Pharmaceuticals, San Diego, CA.
authors.forename: Isan
authors.initials: I
authors.lastname: Chen
authors.affiliation: Pfizer Inc, New Jersey, NJ; Aragon Pharmaceuticals, San Diego, CA.
authors.forename: Edna
authors.initials: E
authors.lastname: Chow-Maneval
authors.affiliation: Pfizer Inc, New Jersey, NJ.
authors.forename: Mariajose
authors.initials: M
authors.lastname: Lechuga
authors.affiliation: Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Smith
authors.affiliation: Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA.
authors.forename: M Dror
authors.initials: MD
authors.lastname: Michaelson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018450:Disease Progression; D000077143:Docetaxel; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use; D007249:Inflammation / Q000276:immunology; D053208:Kaplan-Meier Estimate; D007770:L-Lactate Dehydrogenase / Q000097:blood; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D010919:Placebos / Q000008:administration & dosage; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality*; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D000077210:Sunitinib; D043823:Taxoids / Q000627:therapeutic use
chemical_list: D006454:Hemoglobins; D007211:Indoles; D010919:Placebos; D011758:Pyrroles; D043823:Taxoids; D000077143:Docetaxel; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase; D017430:Prostate-Specific Antigen; D000077210:Sunitinib; D011241:Prednisone
keywords: Advanced prostate cancer; Lymphocytes; Neutrophils; Prognosis; Survival