Prognostic impact of the neutrophil-to-lymphocyte ratio in men with metastatic castration-resistant prostate cancer

Clin Genitourin Cancer. 2014 Oct;12(5):317-24. doi: 10.1016/j.clgc.2014.03.005. Epub 2014 Mar 15.

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.

Conclusion: High NLR may be associated with an independent poor prognostic impact in post-docetaxel patients with mCRPC. These data warrant external validation.

Keywords: Advanced prostate cancer; Lymphocytes; Neutrophils; Prognosis; Survival.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alkaline Phosphatase / blood
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Disease Progression
  • Docetaxel
  • Hemoglobins / metabolism
  • Humans
  • Indoles / adverse effects
  • Indoles / therapeutic use
  • Inflammation / immunology
  • Kaplan-Meier Estimate
  • L-Lactate Dehydrogenase / blood
  • Lymphocyte Count
  • Lymphocytes / cytology
  • Lymphocytes / immunology*
  • Male
  • Middle Aged
  • Neutrophils / cytology
  • Neutrophils / immunology*
  • Placebos / administration & dosage
  • Prednisone / adverse effects
  • Prednisone / therapeutic use
  • Prognosis
  • Proportional Hazards Models
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms, Castration-Resistant / drug therapy
  • Prostatic Neoplasms, Castration-Resistant / immunology*
  • Prostatic Neoplasms, Castration-Resistant / mortality*
  • Pyrroles / adverse effects
  • Pyrroles / therapeutic use
  • Retrospective Studies
  • Sunitinib
  • Taxoids / therapeutic use

Substances

  • Hemoglobins
  • Indoles
  • Placebos
  • Pyrroles
  • Taxoids
  • Docetaxel
  • L-Lactate Dehydrogenase
  • Alkaline Phosphatase
  • Prostate-Specific Antigen
  • Sunitinib
  • Prednisone