Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton (Surrey), UK.
Department of Medical Oncology, Kantonsspital St Gallen, St Gallen, Switzerland.
Ann Oncol. 2015 Apr;26(4):750-755. doi: 10.1093/annonc/mdu587. Epub 2014 Dec 23.
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.
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.
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.
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.
NCT00417079.
中性粒细胞与淋巴细胞比值（NLR）作为癌症相关炎症的指标，已被证实对前列腺癌具有预后价值。本研究旨在探讨 NLR 与二线化疗患者的生存（OS）和反应之间的关系。
我们分析了 TROPIC 试验中转移性去势抵抗性前列腺癌（mCRPC）患者的数据，评估了卡巴他赛与米托蒽醌的疗效。采用 Cox 回归模型探讨基线 NLR（BLNLR）与 OS 的关系，以及 NLR 计数变化与治疗的关系。采用 logistic 回归模型确定 BLNLR 计数与前列腺特异性抗原（PSA）和 RECIST 反应的关系。根据不同值的一致性指数确定最佳 NLR 截断值。
本研究分别纳入了 755、654 和 405 例患者，用于 OS、PSA 和 RECIST 反应分析。中位 OS 为 14.0 个月（95%CI 13.2-14.8）。中位 NLR 为 2.9（IQR：1.9-5.1）。多变量分析（MVA）显示，BLNLR 与生存相关（HR 1.5，95%CI 1.1-2.1，P=0.011），独立于 Halabi 列线图中的变量、治疗臂和皮质类固醇的使用。基于其与生存相关的更高 c 指数，选择 NLR 为 3.0 作为二分类 NLR 的最佳截断值。MVA 显示，BLNLR≥3.0 与 PSA 反应率（40.1% vs 59.9%；P<0.001）和 RECIST 反应率（7.7% vs 15.6%；P=0.022）较低相关。从高（≥3）到低（<3） NLR 的转换与生存改善相关（HR 0.66；95%CI 0.51-0.85；P=0.001），PSA 反应率更高（66.4% vs 33.6%；P=0.000）。基线使用皮质类固醇不会改变 NLR 与生存之间的关系。
NLR 是 CRPC 的有效预后生物标志物，与二线化疗患者的生存、PSA 和 RECIST 反应相关。治疗过程中 NLR 计数的变化可能提示获益。NLR 的预后价值独立于皮质类固醇的既往使用。
临床试验.gov：NCT00417079。
