Department of Urology, David Geffen School of Medicine at University of California, Los Angeles, California.
Institute of Urologic Oncology, David Geffen School of Medicine at University of California, Los Angeles, California.
Cancer Epidemiol Biomarkers Prev. 2019 Jun;28(6):1036-1044. doi: 10.1158/1055-9965.EPI-18-0893. Epub 2018 Dec 28.
Despite extensive research to identify biomarkers of response in patients with non-muscle-invasive bladder cancer (NMIBC), there is no biomarker to date that can serve this purpose. Herein, we report how we leveraged serial urine samples to query a panel of cytokines at varying time points in an attempt to identify predictive biomarkers of response in NMIBC.
Serial urine samples were collected from 50 patients with intermediate- or high-risk NMIBC enrolled in a phase II study, evaluating intravesical BCG ± intradermal HS-410 therapy. Samples were collected at baseline, week 7, week 13, week 28, and at end of treatment. A total of 105 cytokines were analyzed in each sample. To predict outcome of time-to-event (recurrence or progression), univariate and multivariable Cox analyses were performed.
Fifteen patients developed recurrence and 4 patients progressed during the follow-up period. Among clinicopathologic variables, ever-smoker versus nonsmoker status was associated with an improved response rate (HR 0.38; 95% confidence interval (CI), 0.14-0.99; = 0.04). In the most clinically relevant model, the percent change (for 100 units) of IL18-binding protein-a (HR 1.995; 95% CI, 1.16-3.44; = 0.01), IL23 (HR 1.12; 95% CI, 1.01-1.23; = 0.03), IL8 (HR 0.27; 95% CI, 0.07-1.08; = 0.06), and IFNγ-induced protein-10 (HR 0.95; 95% CI, 0.91-0.99; = 0.04) at week 13 from baseline best predicted time to event.
Urinary cytokines provided additional value to clinicopathologic features to predict response to immune-modulating agents in patients with NMIBC.
This study serves as a hypothesis-generating report for future studies to evaluate the role of urine cytokines as a predictive biomarker of response to immune treatments.
尽管已经进行了广泛的研究以确定非肌肉浸润性膀胱癌 (NMIBC) 患者的反应生物标志物，但迄今为止尚无能够实现此目的的生物标志物。在此，我们报告了如何利用连续尿液样本在不同时间点查询一系列细胞因子，试图确定 NMIBC 反应的预测生物标志物。
对 50 名接受 II 期研究评估的中高危 NMIBC 患者连续尿液样本进行收集，评估膀胱内 BCG ± 皮内 HS-410 治疗。样本分别在基线、第 7 周、第 13 周、第 28 周和治疗结束时收集。每个样本分析了 105 种细胞因子。为了预测时间事件（复发或进展）的结果，进行了单变量和多变量 Cox 分析。
50 名患者中有 15 名在随访期间复发，4 名进展。在临床病理变量中，吸烟者与非吸烟者的状态与提高的反应率相关（HR 0.38；95%置信区间 [CI]，0.14-0.99； = 0.04）。在最具临床意义的模型中，白细胞介素 18 结合蛋白-a 的百分比变化（增加 100 单位）（HR 1.995；95%CI，1.16-3.44； = 0.01）、白细胞介素 23（HR 1.12；95%CI，1.01-1.23； = 0.03）、白细胞介素 8（HR 0.27；95%CI，0.07-1.08； = 0.06）和干扰素γ诱导蛋白 10（HR 0.95；95%CI，0.91-0.99； = 0.04）在第 13 周时从基线预测时间事件的最佳预测。
尿液细胞因子为预测非肌肉浸润性膀胱癌患者对免疫调节剂反应的临床病理特征提供了额外的价值。
本研究为未来评估尿液细胞因子作为免疫治疗反应预测生物标志物的作用的研究提供了假设生成报告。
