术前单核细胞与淋巴细胞比值对老年UTUC患者根治术后预后的预测价值

Predictive value of preoperative monocyte-to-lymphocyte ratio in elderly patients with upper urinary tract urothelial carcinoma after radical nephroureterectomy

目的探讨术前单核细胞与淋巴细胞比值(MLR)对老年上尿路尿路上皮癌(UTUC)患者根治术后预后的预测价值。方法回顾性分析2004年3月至2019年2月北京医院收治的168例行根治手术的老年UTUC患者的病例资料,男75例(44.6%),女93例(55.4%)。中位年龄73(69,78)岁。110例(65.5%)术前伴肾积水。肿瘤单发147例(87.5%),多发21例(12.5%)。肿瘤位于肾盂和肾盂-输尿管交界处75例(46.6%),输尿管93例(53.4%)。106例(63.1%)行腹腔镜手术,62例(32.9%)行开放手术。以MLR中位值0.22作为截断值,将患者分为低MLR组(≤0.22)和高MLR组(>0.22)。分析MLR与各临床病理因素的关系。采用Kaplan-Meier法和log-rank检验进行生存分析,并根据病理分级进行亚组分析。采用Cox比例风险模型单因素和多因素分析术前MLR与总生存期(OS)和无进展生存期(PFS)的关系。结果本研究168例,术后随访51.9(19.2,86.9)个月。低MLR组77例,高MLR组91例。高MLR组男性[51例(56.0%)与24例(31.2%)]、腹腔镜手术[64例(70.3%)与42例(54.5%)]比例高于低MLR组(P均<0.05)。单因素分析结果显示,男性(HR=1.793,95%CI 1.003~3.205,P=0.049)、淋巴结阳性(HR=6.809,95%CI 2.124~17.454,P=0.001)和术前高MLR(HR=2.287,95%CI 1.259~4.154,P=0.007)与OS显著相关;男性(HR=1.758,95%CI 1.066~2.902,P=0.027)、淋巴结阳性(HR=6.524,95%CI 2.542~16.748,P<0.001)、淋巴血管侵犯(HR=2.348,95%CI 1.139~4.838,P=0.021)和术前高MLR(HR=2.801,95%CI 1.657~4.735,P<0.001)与PFS相关。多因素分析结果显示,肿瘤部位(HR=2.050,95%CI 1.079~3.892,P=0.028)、淋巴结阳性(HR=6.641,95%CI 1.852~23.811,P=0.004)和MLR(HR=2.089,95%CI 1.062~4.113,P=0.033)是影响老年UTUC患者OS的独立危险因素;肿瘤部位(HR=2.024,95%CI 1.033~3.965,P=0.040)、肿瘤多发(HR=2.992,95%CI 1.161~7.713,P=0.023)、淋巴结阳性(HR=6.454,95%CI 2.026~20.564,P=0.002)和MLR(HR=2.866,95%CI 1.554~5.284,P=0.001)是影响PFS的独立危险因素。采用多因素分析中有意义的危险因素建立术后风险分层模型并绘制生存曲线,结果显示低风险(0个危险因素)、中风险(1个危险因素)、高风险(2~3个危险因素)3个亚组患者的OS(P=0.001)、PFS(P=0.009)差异均有统计学意义。结论术前MLR是影响老年UTUC患者根治术后OS和PFS的独立危险因素之一,高MLR患者预后更差。

Objective To determine the predictive value of preoperative monocyte-to-lymphocyte ratio(MLR)for prognosis in elderly patients with upper tract urothelial carcinoma(UTUC)after radical nephroureterectomy(RNU).Methods A retrospective study was performed on 168 elderly patients who underwent RNU in Beijing Hospital between March 2004 to February 2019.Males accounted for 44.6%(75 patients)and females 55.4%(93 patients)of the patients.Median age at the time of surgery was 73(69-78)years,and 110(65.5%)patients suffered from hydronephrosis.There were 147 cases(87.5%)with single tumor,and 21 cases(12.5%)with multiple tumors,including 75(46.6%)cases in renal pelvis or pelvi-ureteric junction,and 93(53.4%)cases in ureter.Open RNU was performed in 106(63.1%)patients,and laparoscopic method in 62(32.9%)patients.The optimal cutoff value of MLR was set as 0.22 by using the median.χ^(2) test,which was used to detect the association between MLR(≤0.22 vs.>0.22)and clinicopathological variables.Survival analyses were performed using the Kaplan-Meier method and were compared using the log-rank test.Additional subgroup analyses(low grade vs.high grade)were performed according to pathological grade.Univariate and multivariate analysis by Cox’s proportional hazards model was used to determine the significance of MLR in respect to OS and PFS.Results The follow-up period ranged from 19.2 to 86.9 months(median 51.9 months).Next,the cohort was divided into 2 groups,including 77 patients with low MLR(≤0.22)and 91 patients with high MLR(>0.22).High MLR was significantly more frequent in male patients(31.2%vs.56.0%),as well as those undergoing laparoscopic surgery(54.5%vs.70.3%)(All P<0.05).Based on a Cox univariate proportional hazards analysis,male gender(HR=1.793,95%CI 1.003-3.205,P=0.049),presence of lymph node metastasis(HR=6.809,95%CI 2.124-17.454,P=0.001)and high MLR(HR=2.287,95%CI 1.259-4.154,P=0.007)were associated with poor OS.Male gender(HR=1.758,95%CI 1.066-2.902,P=0.027),presence of lymph node metastasis(HR=6.524,95%CI 2.542-16.748,P<0.001),lymphovascular invasion(LVI)(HR=2.348,95%CI 1.139-4.838,P=0.021),high MLR(HR=2.801,95%CI 1.657-4.735,P<0.001)and PLR(HR=1.663,95%CI 1.003-2.757,P=0.049)were significantly associated with subsequent PFS.By multivariate analysis,tumor site(HR=2.050,95%CI 1.079-3.892,P=0.028),lymph node metastasis(HR=6.641,95%CI 1.852-23.811,P=0.004)and MLR(HR=2.089,95%CI 1.062-4.113,P=0.033)were the independent risk factors for OS in elderly patients with UTUC.Tumor side(HR=2.024,95%CI 1.033-3.965,P=0.040),multifocality(HR=2.992,95%CI 1.161-7.713,P=0.023),lymph node metastasis(HR=6.454,95%CI 2.026-20.564,P=0.002)and MLR(HR=2.866,95%CI 1.554-5.284,P=0.001)were associated with PFS.The multivariate analysis of the significant risk factors established a postoperative risk stratification model for OS and PFS.The results showed significant differences among the 3 subgroups of patients with low(0 risk factor),intermediate(1 risk factor),or high risk(2-3 risk factors)(All P<0.05).Conclusion MLR was an independent risk factor for OS and PFS in elderly patients with UTUC and patients with elevated MLR have worsen prognosis.