术前白蛋白碱性磷酸酶比值对根治性膀胱切除术后总体生存期的影响

Prognostic value of albumin-to-alkaline phosphatase ratio before radical cystectomy in patients with bladder cancer

目的探讨术前白蛋白碱性磷酸酶比值(AAPR)与根治性膀胱切除术后患者总体生存期(OS)的关系。方法回顾性分析2007年1月至2015年12月青岛大学附属医院收治的166例膀胱癌患者的临床病理资料。男148例,女18例。年龄(65.1±9.4)岁。伴高血压病31例、糖尿病14例。体质指数(BMI)(24.00±3.32)kg/m^2。肿瘤单发92例,多发74例。肿瘤直径<3 cm者43例,≥3 cm者123例。合并肾积水33例,无肾积水133例。术前AAPR(0.62±0.23)。根据AAPR的三分位点将患者分为低AAPR组55例,AAPR(0.42±0.09);中AAPR组55例,AAPR(0.58±0.05);高AAPR组56例,AAPR(0.86±0.21)。美国麻醉医师协会(ASA)分级1级4例,2级65例,3级86例,4级11例。根治术前患者均行经尿道膀胱肿瘤切除术,病理诊断均为膀胱癌,高级别144例,低级别22例。166例均行根治性膀胱切除术,其中腹腔镜手术140例,开放手术26例。术中行输尿管皮肤造口55例,回肠代膀胱96例,回肠原位新膀胱15例。将AAPR连续性变量和AAPR分组作为原始模型,调整年龄、肿瘤大小、pT分期、pN分期、肾积水、ASA分级、辅助化疗的数据作为校准模型1,在校准模型1基础上增加BMI、肿瘤数目、病理等级的数据作为校准模型2。采用趋势性检验检测不同AAPR组间危险比(HR)变化趋势。分析不同因素分层的AAPR与OS的关系。采用Kaplan-Meier法绘制生存曲线。采用基于广义相加模型的曲线拟合表示AAPR与OS的关系。结果本组166例中位随访63个月,生存95例,死亡71例。3年生存率为61%,5年生存率为50%。术后病理分期:T1期27例,T2期82例,T3期48例,T4期9例;N0期145例,N1期14例,N2期6例,N3期1例。术后52例行辅助化疗。单因素Cox回归分析结果显示,AAPR(HR=0.09,95%CI 0.022~0.391,P=0.001)、高AAPR组(HR=0.40,95%CI 0.216~0.742,P=0.003)、年龄(HR=2.42,95%CI 1.294~4.531,P=0.006)、肿瘤大小(HR=2.11,95%CI 1.112~4.014,P=0.023)、肿瘤数目(HR=0.62,95%CI 0.378~1.022,P=0.061)、pT3期(HR=8.93,95%CI 3.173~25.114,P<0.001)、pT4期(HR=10.39,95%CI 3.110~34.707,P<0.001)、N1期(HR=2.80,95%CI 1.422~5.531,P=0.003)、N3期(HR=17.06,95%CI 2.192~132.863,P=0.007)、病理分级(HR=0.30,95%CI 0.113~0.817,P=0.019)、肾积水(HR=2.36,95%CI 1.406~3.939,P=0.001)、术后辅助化疗(HR=2.66,95%CI 1.674~4.247,P<0.001)均与术后OS相关。调整年龄、肿瘤大小、pT分期、pN分期、肾积水、ASA分级、辅助化疗、BMI、肿瘤数目、病理分级后,Cox回归分析结果显示,与低AAPR组相比,高AAPR组的死亡风险降低约59%(HR=0.406,95%CI 0.200~0.822,P=0.012),AAPR每升高1个单位,死亡风险下降约80%(HR=0.199,95%CI 0.051~0.779,P=0.020)。趋势性检验结果显示,原始模型和校准模型中,AAPR不同分组间OS的HR下降趋势均有统计学意义(P=0.016),提示两者呈线性关系。调整年龄、肿瘤大小、pT分期、pN分期、肾积水、ASA分级、辅助化疗、BMI、肿瘤数目、病理分级后,曲线拟合图显示,AAPR与OS呈线性相关,随AAPR升高,术后死亡风险下降,OS延长。结论AAPR与膀胱肿瘤患者根治性膀胱切除术后的OS成线性相关,随AAPR升高,患者术后死亡风险下降,OS延长。

Objective To investigate the relationship between preoperative albumin-to-alkaline phosphatase ratio and overall survival(OS)after radical cystectomy of bladder cancer.Methods The clinical date of patients with bladder cancer who underwent radical cystectomy and urinary diversion and confirmed by pathology from Jan 2007 to Dec 2015 were analyzed retrospectively,with 140 cases undergoing laparoscopic surgery and 26 cases undergoing open surgery.There were 148 males and 18 females,aged was 33-85 years,with an average age of(65.1±9.4)years.There were 55 cases of cutaneous ureterostomy,96 cases of Brick diversion with ileum,and 15 cases of ileal neobladder.The AAPR range 0.03-1.67,with an average 0.62±0.23,and body mass index(BMI)was 16.79-32.65 kg/m^2,with an average of(24.00±3.32)kg/m2.There were 33 cases with hydronephrosis and 133 no hydronephrosis,31 cases with hypertension and 135 cases no hypertension,and 14 cases with diabetes and 152 cases no diabetes.Four cases were classified as grade 0,65 cases as grade 1,86 cases as grade 2,and 11 cases as grade 3.Based on the preoperative AAPR(0.62±0.23),they were divided into three groups,with 55 cases in the low AAPR(0.42±0.09)group,55 cases in the middle AAPR(0.58±0.05)group,and 56 cases in the high AAPR(0.86±0.21)group.Cox proportional hazards regression methodology were used to evaluate the relationship between preoperative AAPR and overall survival.Survival analysis was conducted using the Kaplan-Meier method and compared with the log-rank test.Results 166 patients were followed up for 1-144 months,with a median of 63 months,and 71 cases died and 95 survived.The median serum AAPR level in all cases was 0.59(range 0.03-1.67).Results of univariate Cox regression model revealed that AAPR(HR=0.09,95%CI 0.022-0.391,P=0.001),high AAPR(HR=0.40,95%CI 0.216-0.742,P=0.003),age(HR=2.42,95%CI 1.294-4.531,P=0.006),tumor size(HR=2.11,95%CI 1.112-4.014,P=0.023),pT3 stage(HR=8.93,95%CI 3.173-25.114,P<0.001),pT4 stage(HR=10.39,95%CI 3.110-34.707,P<0.001),pN1 stage(HR=2.80,95%CI 1.422-5.531,P=0.003),pN3 stage(HR=17.06,95%CI 2.192-132.863,P=0.007),pathological grade(HR=0.30,95%CI 0.113-0.817,P=0.019),hydronephrosis(HR=2.36,95%CI 1.406-3.939,P=0.001),adjuvant chemotherapy(HR=2.66,95%CI 1.674-4.247,P<0.001)were associated with OS.Compared with patients in the lowest of AAPR,the risk for death in the highest AAPR group decreased about 59%(HR=0.406,95%CI 0.200-0.822,P=0.012)after adjustment for age,BMI,tumor size,number of tumor,T category,N category,pathological grade,hydronephrosis,ASA level,adjuvant chemotherapy in multiple Cox regression models.Each unit increase in the AAPR was associated with about 80%decreased risk of death(HR=0.199,95%CI 0.051-0.779,P=0.020)after adjusting for the confounding variables.After adjusting for age,BMI,tumor size,number of tumor,T category,N category,pathological grade,hydronephrosis,ASA level,adjuvant chemotherapy,the curve fitting results showed that with the increase of AAPR,the risk of death decreased and the overall survival prolonged.Consistent with the linear trend test results,the relationship between AAPR and OS is linear.Conclusions AAPR was associated with overall survival of patients who underwent radical cystectomy of bladder cancer.