Prostate Cancer Targeted Therapy Group, Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom.
Medical Oncology Service, Hospital Universitario La Fe, Valencia, Spain.
Clin Genitourin Cancer. 2017 Dec;15(6):678-684.e1. doi: 10.1016/j.clgc.2017.05.012. Epub 2017 May 10.
The neutrophil to lymphocyte ratio (NLR) has been shown to be highly prognostic across many tumor types, and predictive of treatment outcome in advanced prostate cancer, and has been postulated to be an indirect measure of tumor inflammation. We evaluated the effect of low-dose steroids on NLR in men suffering from castration-resistant prostate cancer (CRPC).
The NLR was evaluated in a prospective randomized phase II trial that compared prednisolone 5 mg twice daily and dexamethasone 0.5 mg daily administered to 75 chemotherapy and abiraterone/enzalutamide-naive CRPC patients. NLR was examined at baseline (BL), after 6 and 12 weeks of corticosteroid treatment; associations with >50% prostate-specific antigen (PSA) response, duration of response (PSA progression-free interval), and overall survival (OS) were tested using logistic regression and Cox regression analysis.
The median NLR for all evaluable patients was 2.6 at BL; 2.9 at 6 weeks; and 4.0 at 12 weeks. After low-dose corticosteroid initiation, 46 patients had a decline in PSA with 24 confirmed responders. BL NLR (log10) associated with a PSA response (odds ratio, .029, 95% confidence interval [CI], .002-.493; P = .014), and with the extent of the PSA decline (P = .009). A favorable BL NLR (less than median) associated with a 5.5-fold higher odds of a PSA >50% response (95% CI, 1.3-23.9; P = .02). Higher BL NLR (log10) associated with a shorter time to PSA progression (hazard ratio [HR], 9.5; 95% CI, 2.3-39.9; P = .002). In multivariate analysis BL NLR as a discrete variable was independently associated with PSA progression (HR, 3.5; 95% CI, 1.5-8.1; P = .003). NLR at 6 weeks was also associated with duration of benefit; in the favorable NLR category time to PSA progression was 10.8 months, for those who converted to an unfavorable (greater than median) category 4.5 months, and for those remaining in a unfavorable category only 1.5 months (95% CI, 0.5-2.5; P = .003). OS was 33.1 months (95% CI, 24.2-42.0) and 21.9 months (95% CI, 19.3-24.4) for those with an favorable and unfavorable BL NLR, respectively.
Treatment-naive CRPC patients with a high BL or during-treatment NLR appear not to benefit from low-dose corticosteroids. The immunological implications of an unfavorable NLR, and whether corticosteroids might drive prostate cancer progression in patients harboring a high NLR, warrant further study.
中性粒细胞与淋巴细胞比值（NLR）已被证明在许多肿瘤类型中具有高度预后价值，并可预测晚期前列腺癌的治疗结果，并且被推测为肿瘤炎症的间接衡量指标。我们评估了低剂量类固醇对接受去势抵抗性前列腺癌（CRPC）治疗的男性中 NLR 的影响。
在一项前瞻性随机 II 期试验中评估了 NLR，该试验比较了泼尼松 5mg 每日两次和地塞米松 0.5mg 每日治疗 75 例化疗和阿比特龙/恩杂鲁胺初治 CRPC 患者。在基线（BL）、皮质类固醇治疗 6 周和 12 周时检查 NLR；使用逻辑回归和 Cox 回归分析检验与 >50%前列腺特异性抗原（PSA）反应、反应持续时间（PSA 无进展间隔）和总生存（OS）相关的因素。
所有可评估患者的中位 NLR 为 BL 时为 2.6；6 周时为 2.9；12 周时为 4.0。开始低剂量皮质类固醇治疗后，46 例 PSA 下降，24 例确认为应答者。BL NLR（log10）与 PSA 反应相关（优势比，.029，95%置信区间[CI]，.002-.493；P=0.014），与 PSA 下降程度相关（P=0.009）。有利的 BL NLR（低于中位数）与 PSA >50%反应的可能性高 5.5 倍（95%CI，1.3-23.9；P=0.02）。更高的 BL NLR（log10）与 PSA 进展的时间更短相关（风险比[HR]，9.5；95%CI，2.3-39.9；P=0.002）。多变量分析显示，BL NLR 作为离散变量与 PSA 进展独立相关（HR，3.5；95%CI，1.5-8.1；P=0.003）。6 周时的 NLR 也与获益持续时间相关；在有利的 NLR 类别中，PSA 进展的时间为 10.8 个月，对于那些转换为不利（大于中位数）类别的患者为 4.5 个月，对于那些仍处于不利类别的患者仅为 1.5 个月（95%CI，0.5-2.5；P=0.003）。OS 为 33.1 个月（95%CI，24.2-42.0）和 21.9 个月（95%CI，19.3-24.4），分别为 BL NLR 有利和不利的患者。
初治 CRPC 患者的 BL 或治疗期间 NLR 较高似乎不能从低剂量皮质类固醇中获益。不利 NLR 的免疫学意义，以及皮质类固醇是否会导致 NLR 较高的患者的前列腺癌进展，值得进一步研究。
