title: Baseline neutrophil-lymphocyte ratio (NLR) is associated with survival and response to treatment with second-line chemotherapy for advanced prostate cancer independent of baseline steroid use.
abstract: BACKGROUND
  The neutrophil-lymphocyte ratio (NLR), proposed as an indicator of cancer-related inflammation, has known prognostic value in prostate cancer. We examine its association with survival (OS) and response in patients treated with second-line chemotherapy.
  
  
  METHODS
  We analysed patients with metastatic castration-resistant prostate cancer (mCRPC) treated in the TROPIC trial, evaluating cabazitaxel versus mitoxantrone. Cox regression models were used to investigate the association of baseline NLR (BLNLR) with OS and the significance of a change in NLR count with treatment. Logistic regression models were used to determine the association of BLNLR counts with prostate specific antigen (PSA) and RECIST responses. The optimal NLR cut-off was established based on the concordance index of different values.
  
  
  RESULTS
  Data from 755, 654 and 405 patients was available for OS, PSA and RECIST response analysis respectively. Median OS was 14.0 months [95% confidence interval (CI) 13.2-14.8]. Median NLR was 2.9 (IQR: 1.9-5.1). BLNLR was associated with survival (HR 1.5, 95% CI 1.1-2.1, P = 0.011) in multivariable analysis (MVA) independently of variables included in the Halabi nomogram, treatment arm and corticosteroid use. The optimal cut-off for a dichotomous NLR was selected at 3.0 based on its higher c-index related to survival. BLNLR ≥3.0 was associated with lower PSA response (40.1% versus 59.9%; P < 0.001) and RECIST response (7.7% versus 15.6%, P = 0.022) in MVA. Conversion from high (≥3) to low (<3) NLR was associated with improved survival (HR 0.66; 95% CI 0.51-0.85; P = 0.001) and higher PSA response rates (66.4% versus 33.6%; P = 0.000). Use of corticosteroids at baseline did not modify the association between NLR and survival.
  
  
  CONCLUSIONS
  NLR is a valid prognostic biomarker in CRPC and is associated with survival, PSA and RECIST responses in patients treated with second-line chemotherapy. Changes in NLR counts with treatment may indicate benefit. NLR prognostic value is independent of prior use of corticosteroids.
  
  
  BACKGROUND
  NCT00417079.
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton (Surrey), UK.
authors.forename: D
authors.initials: D
authors.lastname: Lorente
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton (Surrey), UK.
authors.forename: J
authors.initials: J
authors.lastname: Mateo
authors.affiliation: Department of Medical Oncology, Kantonsspital St Gallen, St Gallen, Switzerland.
authors.forename: A J
authors.initials: AJ
authors.lastname: Templeton
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton (Surrey), UK.
authors.forename: Z
authors.initials: Z
authors.lastname: Zafeiriou
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton (Surrey), UK.
authors.forename: D
authors.initials: D
authors.lastname: Bianchini
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton (Surrey), UK.
authors.forename: R
authors.initials: R
authors.lastname: Ferraldeschi
authors.affiliation: Department of Clinical Oncology, Bristol Haematology and Oncology Centre, Bristol, UK.
authors.forename: A
authors.initials: A
authors.lastname: Bahl
authors.affiliation: Oncology, Sanofi Oncology, Cambridge.
authors.forename: L
authors.initials: L
authors.lastname: Shen
authors.affiliation: Oncology, Sanofi Oncology, Cambridge.
authors.forename: Z
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Medicine: Section of Hematology & Medical Oncology and Department of Urology, Tulane University, New Orleans, USA.
authors.forename: O
authors.initials: O
authors.lastname: Sartor
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton (Surrey), UK. Electronic address: johann.debono@icr.ac.uk.
authors.forename: J S
authors.initials: JS
authors.lastname: de Bono
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006801:Humans; D008214:Lymphocytes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009367:Neoplasm Staging; D009504:Neutrophils / Q000473:pathology*; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D012189:Retrospective Studies; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D000305:Adrenal Cortex Hormones; D043823:Taxoids; C552428:cabazitaxel; D008942:Mitoxantrone; D017430:Prostate-Specific Antigen
keywords: cabazitaxel; castration-resistant prostate cancer; neutrophil–lymphocyte ratio; prognostic biomarker; steroids; treatment response