非肌层浸润性膀胱癌TURBT术后复发风险预测模型的建立和验证

Establishment and validation of a recurrence risk prediction model for non-muscle invasive bladder cancer after TURBT

目的构建非肌层浸润性膀胱癌(NMIBC)患者经尿道膀胱肿瘤电切术(TURBT)后复发风险的定量预测模型并进行验证。方法选取2014年12月至2019年12月在苏州大学附属张家港医院诊断为NMIBC且接受TURBT治疗的310例患者,随机将其分为模型组(170例)和验证组(140例)。同时将模型组分为复发组(90例)和未复发组(80例)进行亚组分析。首先采用欧洲癌症研究与治疗组织(EORTC)风险分层将模型组分为低风险组(21例)、中风险组(119例)和高风险组(30例),应用Kaplan-Meier生存曲线比较各亚组间无复发生存(RFS)的差异;然后比较复发组与未复发组患者的临床资料、肿瘤特征(包括TNM分期、最大径、组织学分级)和生化标志物[包括膀胱癌特异性核基质蛋白4(BLCA-4)、膀胱肿瘤抗原(BTA)、核基质蛋白22(NMP22)、癌胚抗原(CEA)];采用多因素logistic回归分析筛选主要危险因素,根据权重赋值建立新型定量评分系统,采用受试者工作特征(ROC)曲线分析评分系统在验证组中的诊断效能;最后根据评分系统的最佳临界值对模型组进行危险分层,再次比较RFS的差异性。结果模型组基于EORTC风险分层的低、中、高风险组间RFS比较,差异无统计学意义(P>0.05)。单因素分析结果显示,复发组的年龄和家族史比例较未复发组显著升高,化疗药物膀胱灌注比例显著降低,T1期显著增多,肿瘤最大径显著增大,低分化比例显著增多,BLCA-4、BTA、NMP22和CEA水平均显著升高(均P<0.05)。多因素logistic回归分析结果显示,家族史、化疗药物膀胱灌注、肿瘤最大径、低分化、BLCA-4、BTA、NMP22和CEA水平均是肿瘤复发的主要危险因素(均P<0.05)。ROC曲线分析结果显示,评分系统预测验证组复发的准确性为0.865,临界值为3.8分(总分6~7分),>4分为高风险,<4分为低风险。模型组中高风险患者的RFS明显低于低风险患者(χ^(2)=6.235,P=0.003);验证组中高风险患者的RFS明显低于低风险患者(χ^(2)=5.867,P=0.007)。结论我国NMIBC患者的TURBT后复发风险应用EORTC的准确性欠佳,家族史、化疗药物膀胱灌注、肿瘤最大径、低分化、BLCA-4、BTA、NMP22和CEA水平可能是肿瘤复发的主要危险因素,构建的定量评分系统对预测肿瘤复发具有较好的准确性,对评估RFS也有较好的应用价值。

Objective To establish and validate a quantitative prediction model for recurrence risk of non-muscle invasive bladder cancer(NMIBC)patients after transurethral resection of bladder tumor(TURBT).Methods From December 2014 to December 2019,a total of 310 patients with NMIBC receiving TURBT were chosed for the retrospective study,they were randomly divided into model group(170 cases)and verification group(140 cases).The model group was divided into relapse group(90 cases)and non-recurrence group(80 cases)for subgroup analysis.The European Organization for Research and Treatment of Cancer(EORTC)risk stratification was used to divide the model group into low risk group(21 cases),medium risk group(119 cases)and high risk group(30 cases).The difference in RFS was compared by Kaplan-Meier survival curve.Then,clinical data,tumor characteristics and biochemical markers were compared between the two groups.Multivariate logistic regression analysis was used to screen the main risk factors,a new quantitative scoring system was established according to weight assignment,and receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficiency of the scoring system in the verification group.Finally,according to the optimal critical value of the scoring system,the risk stratification of model groups was carried out,and the difference of RFS survival curves was compared again.Results There was no significant difference in RFS between model groups based on EORTC risk stratification(P>0.05).Multivariate logistic regression analysis showed that family history,chemotherapy drug bladder perfusion,maximum diameter,low differentiation,BLCA-4,BTA,NMP22 and CEA levels were the main risk factors for tumor recurrence(all P<0.05).ROC analysis showed that the accuracy of the scoring system in predicting recurrence in the verification group was 0.865,and the critical value was 3.8 scores(total score 6~7 scores).>4 was classified as high risk and<4 was classified as low risk.RFS of high risk patients in the model group was significantly lower than that of low risk patients(χ^(2)=6.235,P=0.003).The RFS of high-risk patients in the verification group was significantly lower than that of lowrisk patients(χ^(2)=5.867,P=0.007).Conclusions EORTC is not accurate for patients with NMIBC after TURBT in China.Family history,bladder perfusion,maximum diameter,low differentiation,BLCA-4,BTA,NMP22 and CEA levels may be the main risk factors to tumor recurrence.The quantitative scoring system has a good accuracy for the prediction of tumor recurrence,and has a good application value for RFS evaluation.