Department of Urology.
Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada; Department of Medical Oncology and Hematology, Kantonsspital St Gallen, St Gallen, Switzerland.
Ann Oncol. 2015 Apr;26(4):743-749. doi: 10.1093/annonc/mdu569. Epub 2014 Dec 15.
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.
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.
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.
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.
NCT00519285.
中性粒细胞与淋巴细胞比值（NLR）是宿主炎症的标志物，与几种实体瘤的不良预后相关。在这里，我们研究了衍生 NLR（dNLR）和初始雄激素剥夺治疗（ADT）持续时间与接受一线化疗的转移性去势抵抗性前列腺癌（mCRPC）男性生存的关系。
来自多国随机 III 期研究 VENICE 和 TAX327 的数据共纳入 2230 名 mCRPC 男性，随机接受一线化疗，分别作为训练集和验证集。通过多变量 Cox 回归分析，在训练集中根据体能状态和治疗臂分层，评估 dNLR 和初始 ADT 持续时间与总生存期（OS）的相关性。然后在验证集中测试该模型。随后，我们根据 dNLR 和初始 ADT 持续时间，研究了 docetaxel 在亚组中对 OS 的治疗效果。
在训练集中，dNLR≥中位数（2）和初始 ADT 持续时间<中位数（15 个月）与死亡风险增加相关[风险比（HR）1.29；95%置信区间（CI）1.11-1.50，P<0.001 和 HR 1.41；95%CI 1.21-1.64，P<0.001]，调整年龄、碱性磷酸酶、血红蛋白和基线疼痛后。在验证集中，dNLR 仍然是 OS 的独立预后因素（HR 1.43；95%CI 1.20-1.70，P<0.001），而初始 ADT 持续时间不是（HR 1.16；95%CI 0.97-1.37，P=0.10）。在 TAX327 研究的亚组分析中，docetaxel 改善了 OS，与 dNLR 和初始 ADT 持续时间无关。
在两项随机 III 期试验中，dNLR 对接受一线化疗的 mCRPC 男性的 OS 具有预后意义。高 dNLR（≥2）与较短的生存期相关，无论接受何种治疗。这种易于获得的生物标志物可能有助于未来临床试验中的风险分层，并可纳入预后列线图。
NCT00519285。
