Pre-treatment lymphocytopaenia is an adverse prognostic biomarker in muscle-invasive and advanced bladder cancer
Pre-treatment lymphocytopaenia is an adverse prognostic biomarker in muscle-invasive and advanced bladder cancer
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DOI：
10.1093/annonc/mdv546
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发表时间：
2016-02-01
影响因子：
50.5
通讯作者：
Choudhury, A.
中科院分区：
文献类型：
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作者：
Joseph, N.;Dovedi, S. J.;Choudhury, A.
背景资料：治疗前淋巴细胞减少症可能由肿瘤微环境分泌的细胞因子引起，与侵袭性肿瘤生物学相关。我们试图建立在肌肉浸润性和晚期膀胱cancer.Patients和方法的淋巴细胞减少症的预后意义：74例肌肉浸润性膀胱癌根治性放化疗和131例晚期膀胱癌姑息性化疗治疗的患者被纳入本研究。记录治疗第1天的绝对淋巴细胞计数。肌层浸润性膀胱癌队列中的浸润性局部或全身复发和晚期膀胱癌队列中的全因死亡率被定义为生存终点。受试者工作特征（ROC）曲线分析用于确定肌肉浸润性膀胱癌队列中定义淋巴细胞减少的截止值，然后在评估以下变量的模型中进行多变量分析：贫血、嗜中性粒细胞增多、肿瘤分期、肾积水和新辅助化疗。随后，在分析以下预后变量的晚期膀胱癌队列的多变量模型中评估淋巴细胞减少症：嗜中性粒细胞增多症、贫血、体能状态和骨或内脏转移的存在。结果：在肌层浸润性膀胱癌队列中，绝对淋巴细胞计数1.5 × 10（9）/l被确定为ROC曲线分析的截止值，多变量分析显示，在该队列中，只有淋巴细胞减少预测预后较差。在晚期膀胱癌队列中，淋巴细胞减少[风险比（HR）1.6，95%置信区间（CI）1.1-2.4; P = 0.02]和体力状态（HR 1.7，95% CI 1.0-2.7; P = 0.047）是二元变量多变量模型中的不良预后因素。淋巴细胞绝对计数是唯一有意义的因素分析时，作为一个连续变量（HR 0.66，95%CI 0.5-0.87; P = 0.003）。结论：治疗前淋巴细胞减少是一个独立的不良预后因素在肌层浸润性和晚期膀胱癌。它可能是癌症诱导的免疫抑制的表现，驱动肿瘤进展。
Background: Pre-treatment lymphocytopaenia may result from cytokines secreted by the tumour microenvironment in association with aggressive tumour biology. We sought to establish the prognostic significance of lymphocytopaenia in muscle-invasive and advanced bladder cancer.Patients and methods: Seventy-four patients with muscle-invasive bladder cancer treated with radical chemoradiotherapy and 131 patients with advanced bladder cancer treated with palliative chemotherapy were included in the study. The absolute lymphocyte count on the first day of treatment was recorded. Invasive local or systemic recurrence in the muscle-invasive bladder cancer cohort and all-cause mortality in the advanced bladder cancer cohort were defined as survival end points. Receiver operating characteristic (ROC) curve analysis was utilized to determine the cut-off for defining lymphocytopaenia in the muscle-invasive bladder cancer cohort followed by multivariable analysis in a model evaluating the following variables: anaemia, neutrophilia, tumour stage, hydronephrosis and neoadjuvant chemotherapy. Subsequently, lymphocytopaenia was assessed in a multivariable model of the advanced bladder cancer cohort analysing the following prognostic variables: neutrophilia, anaemia, performance status and presence of bone or visceral metastases. A further analysis was carried out evaluating absolute lymphocyte count as a continuous variable.Results: An absolute lymphocyte count of 1.5 x 10(9)/l was determined as the cut-off on ROC curve analysis in the muscle-invasive bladder cancer cohort, and multivariate analysis revealed that only lymphocytopaenia was predictive for inferior outcome in this cohort. In the advanced bladder cancer cohort, lymphocytopaenia [hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.1-2.4; P = 0.02] and performance status (HR 1.7, 95% CI 1.0-2.7; P = 0.047) were adverse prognostic factors in the binary variable multivariate model. Absolute lymphocyte count was the sole significant factor when analysed as a continuous variable (HR 0.66, 95% CI 0.5-0.87; P = 0.003).Conclusion: Pre-treatment lymphocytopaenia is an independent adverse prognostic factor in both muscle-invasive and advanced bladder cancer. It may be a manifestation of cancer-induced immune suppression driving tumour progression.