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
Menée à partir des données de deux essais de phase III incluant au total 2 230 patients recevant une chimiothérapie de première ligne pour traiter un cancer métastatique de la prostate résistant à la castration, cette étude évalue l'association entre un indicateur, dérivé du rapport entre le nombre de neutrophiles et le nombre de lymphocytes, la durée du traitement anti-androgénique initial et la survie des patients
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.
Patients and 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 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 (HR=1.29;95%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.
Conclusion : 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.
Annals of Oncology , résumé, 2014