title: Neutrophil-to-lymphocyte ratio as a prognostic biomarker for men with metastatic castration-resistant prostate cancer receiving first-line chemotherapy: data from two randomized phase III trials.
abstract: BACKGROUND
  The neutrophil-to-lymphocyte ratio (NLR), a marker of host inflammation, has been associated with poor outcome in several solid tumors. Here, we investigated associations of the derived NLR (dNLR) and duration of initial androgen deprivation therapy (ADT) with survival of men with metastatic castration-resistant prostate cancer (mCRPC) receiving first-line chemotherapy.
  
  
  METHODS
  Data from the multinational randomized phase III studies VENICE and TAX327 included a total of 2230 men with mCRPC randomized to receive first-line chemotherapy, and were used as training and validation sets, respectively. Associations of dNLR and duration of initial ADT with overall survival (OS) were evaluated by multivariable Cox regression analysis in the training set stratified for performance status and treatment arm. The model was then tested in the validation set. Subsequently, we investigated the treatment effect of docetaxel on OS in subgroups according to dNLR and duration of initial ADT.
  
  
  RESULTS
  In the training set, both dNLR ≥median (2) and duration of initial ADT <median (15 months) were associated with increased risk of death [hazard ratio (HR) 1.29; 95% confidence interval (CI) 1.11-1.50, P < 0.001 and HR 1.41; 95% CI 1.21-1.64, P < 0.001, respectively] after adjustment for age, alkaline phosphatase, hemoglobin, and pain at baseline. In the validation set, dNLR remained an independent prognostic factor for OS (HR 1.43; 95% CI 1.20-1.70, P < 0.001), whereas duration of initial ADT was not (HR 1.16; 95% CI 0.97-1.37, P = 0.10). In subgroup analyses of the TAX327 study, docetaxel improved OS irrespective of dNLR and duration of initial ADT.
  
  
  CONCLUSIONS
  The dNLR was prognostic for OS in men with mCRPC receiving first-line chemotherapy in two randomized phase III trials. A high dNLR (≥2) was associated with shorter survival irrespective of the received treatment. This readily available biomarker may serve for risk stratification in future clinical trials and could be incorporated into prognostic nomograms.
  
  
  BACKGROUND
  NCT00519285.
authors.affiliation: Department of Urology. Electronic address: r.vansoest@erasmusmc.nl.
authors.forename: R J
authors.initials: RJ
authors.lastname: van Soest
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada; Department of Medical Oncology and Hematology, Kantonsspital St Gallen, St Gallen, Switzerland.
authors.forename: A J
authors.initials: AJ
authors.lastname: Templeton
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: F E
authors.initials: FE
authors.lastname: Vera-Badillo
authors.affiliation: Statprocess, Port-Mort, France.
authors.forename: F
authors.initials: F
authors.lastname: Mercier
authors.affiliation: UAB Comprehensive Cancer Center, University of Alabama, Birmingham, USA.
authors.forename: G
authors.initials: G
authors.lastname: Sonpavde
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Amir
authors.affiliation: Department of Urology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Tombal
authors.affiliation: Depertment of Oncology, Royal Melbourne Hospital, Melbourne, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Rosenthal
authors.affiliation: Sydney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Eisenberger
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: I F
authors.initials: IF
authors.lastname: Tannock
authors.affiliation: Department of Medical Oncology, Erasmus University Medical Center and Cancer Institute, Rotterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: de Wit
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000556:secondary*; D000077143:Docetaxel; D005500:Follow-Up Studies; D006801:Humans; D007390:International Agencies; D008214:Lymphocytes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009504:Neutrophils / Q000473:pathology*; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D011241:Prednisone
keywords: androgen deprivation therapy; docetaxel; metastatic castration-resistant prostate cancer; neutrophil-to-lymphocyte ratio