NLR及PLR对晚期尿路上皮癌免疫治疗疗效和预后的预测价值

Predictive value of NLR and PLR for outcome after immunotherapy in advanced urothelial carcinoma

摘要:

目的 探讨外周血中性粒细胞与淋巴细胞比值（neutrophil to lymphocyte ratio，NLR）和血小板与淋巴细胞比值（platelet to lymphocyte ratio，PLR）对晚期尿路上皮癌免疫治疗疗效和预后的预测价值。方法 回顾性分析2019年9月至2022年7月接受过免疫检查点抑制剂治疗的晚期尿路上皮癌患者的临床资料，绘制受试者工作特征曲线，根据曲线下面积（area under the curve，AUC）筛选的最佳截断值分组，应用Kaplan-Meier生存分析比较组间生存差异，运用Cox模型进行多因素分析筛选出独立预测因素。结果 共纳入57例患者，经3周期免疫治疗后NLR较治疗前显著下降（P<0.001），分别为2.40±1.08和3.05±1.07；而治疗前后PLR无明显变化（P=0.402），分别为226.41±111.70和246.97±113.17；外周血中治疗前后NLR、PLR及NLR变化幅度的AUC分别为0.829 1（P=0.004）、0.889 6（P<0.001）、0.743 6（P=0.003）、0.740 4（P<0.001）、0.798 4（P<0.001）。生存分析显示：治疗前NLR≥3.17（3.5个月vs. 未达到，P<0.001）、治疗前PLR≥284.40（5.7个月vs. 9.5个月，P=0.011）、治疗后NLR≥2.41（4.8个月vs. 9.9个月，P<0.001）及NLR变化幅度<19.8%（5.8个月vs. 9.5个月，P=0.004）与较差的PFS相关，而一线免疫联合化疗具有更好的PFS（9.3个月vs. 6.0个月，P=0.006），且联合治疗组NLR变化更为显著（P=0.034）。Cox多因素分析表明治疗前NLR、NLR变化幅度及合并化疗与否是晚期尿路上皮癌免疫治疗PFS的独立预测因素（P<0.05）。结论 治疗前高NLR及PLR水平预示着不良预后，一线免疫联合化疗能显著降低NLR，延长患者PFS，而NLR及其动态变化是晚期尿路上皮癌免疫治疗的独立预测因素。

Abstract:

Objective To explore the value of peripheral blood neutrophil-to-lymphocyte ratio（NLR） and platelet-to-lymphocyte ratio（PLR） in predicting the outcome after immunotherapy for advanced urothelial carcinoma.Methods We retrospectively analyzed the clinical data of patients with advanced urothelial carcinoma treated with immune checkpoint inhibitors from September 2019 to July 2022. The patients were grouped according to the cut-off value derived from the area under the curve（AUC）. The Kaplan-Meier method was used to compare the survival of the groups. A multivariable Cox model was used to determine independent predictive factors.Results A total of 57 patients were included. After three cycles of immunotherapy，NLR was significantly decreased（pre-treatment 2.40±1.08 vs. post-treatment 3.05±1.07，P<0.001）. There was no significant change in PLR（pre-treatment 226.41±111.70 vs. post-treatment 246.97±113.17，P=0.402）. The AUC values of pre-NLR，post-NLR，pre-PLR，post-PLR，and delta-NLR（change in NLR） were 0.829 1（P=0.004），0.889 6（P<0.001），0.743 6（P=0.003），0.740 4（P<0.001），and 0.798 4（P<0.001），respectively. The survival analysis showed that pre-NLR ≥3.17（3.5 months vs. not achieved，P<0.001），pre-PLR≥284.40（5.7 months vs. 9.5 months，P=0.011），post-NLR ≥2.41（4.8 months vs. 9.9 months，P<0.001），and delta-NLR<19.8%（5.8 months vs. 9.5 months，P=0.004） were significantly associated with a poorer PFS；first-line immunotherapy combined with chemotherapy produced a better PFS（9.3 months vs. 6.0 months，P=0.006），and NLR change was significantly greater in patients with combined treatment（P=0.034）. The multivariable Cox analysis showed that pre-NLR，delta-NLR，and whether chemotherapy was combined were independent predictors of PFS after immunotherapy in advanced urothelial carcinoma（P<0.05）.Conclusion High levels of NLR and PLR before treatment indicate a poor prognosis. First-line immunotherapy combined with chemotherapy can reduce NLR and prolonging patients’ PFS. NLR and its change are independent predictors of outcome after immunotherapy in advanced urothelial carcinoma.