中高危非肌层浸润性膀胱癌卡介苗灌注治疗后复发的临床预测模型构建与验证  

Development and validation of clinical prediction model for post-treatment recurrence in high-risk non-muscle invasive bladder cancer after BCG intravesical instillation

作　　者：王海涛 罗伟铭 陈剑[1] 张健 冉强 徐静 金俊豪 敖杨坤 王亚鹏 张俊英 谢秋波 兰卫华[1] 刘秋礼 WANG Haitao;LUO Weiming;CHEN Jian;ZHANG Jian;RAN Qiang;XU Jing;JIN Junhao;AO Yangkun;WANG Yapeng;ZHANG Junying;XIE Qiubo;LAN Weihua;LIU Qiuli(Department of Urology,Army Medical Center of PLA/Daping Hospital of Third Military Medical University,Chongqing;Chongqing Medical and Pharmaceutical College,Chongqing;Department of Urology,General Hospital of Central Theater Command,Wuhan,Hubei,China)

机构地区：[1]陆军特色医学中心(第三军医大学大坪医院)泌尿外科,重庆 [2]重庆医药高等专科学校,重庆 [3]中国人民解放军中部战区总医院泌尿外科,湖北武汉

出　　处：《陆军军医大学学报》2025年第9期959-968,共10页Journal of Army Medical University

基　　金：国家自然科学基金面上项目(82172721,82372758)。

摘　　要：目的 探讨卡介苗(Bacille Calmette-Guérin, BCG)灌注治疗在中高危非肌层浸润性膀胱癌(non-muscle invasive bladder cancer,NMIBC)患者电切术后疗效的影响因素,并构建BCG灌注治疗后复发的预测模型。方法 本研究采用回顾性队列研究的研究方法,研究对象为确诊为中高危NMIBC并经电切术后接受规律BCG灌注治疗的患者,训练集为2018年1月至2023年12月在陆军特色医学中心泌尿外科就诊的110例患者,外部验证集为2015年1月至2020年12月在中国人民解放军中部战区总医院泌尿外科就诊的52例患者。共纳入17项指标,采用单因素、多因素Cox回归分析BCG灌注治疗后复发的影响因素,并构建1、3和5年列线图预测模型。通过预后校准曲线、决策曲线分析和受试者操作特征曲线进行内部和外部验证,对模型的预测效能和临床实用性进行评价。结果 训练集人群中26例患者(23.64%)在随访期间出现复发,中位无复发生存期为32.00(18.00~50.50)个月。单因素Cox回归分析提示血小板计数、嗜酸性粒细胞与淋巴细胞比值(eosinophil to lymphocyte ratio,ELR)、中性粒细胞与淋巴细胞比值(neutrophil to lymphocyte ratio,NLR)、血小板与淋巴细胞比值(platelet to lymphocyte ratio,PLR)、系统性炎症指数(systemic immune inflammation index,SII)、中性粒细胞与单核细胞之和与淋巴细胞比值(neutrophil-monocyte to lymphocyte ratio, NMLR)、病理分期T1期(pathological T1 stage,pT1)和血红蛋白、白蛋白、淋巴细胞和血小板计数(hemoglobin, albumin, lymphocyte, and platelet,HALP)的组合评分是BCG灌注治疗后复发的潜在影响因素。多因素Cox回归分析提示高HALP评分(HR=0.185,95%CI:0.046~0.736, P=0.017)是BCG灌注治疗后复发的独立保护性因素,高ELR(HR=3.599,95%CI:1.505~8.608, P=0.004)和pT1(HR=3.240,95%CI:1.191~8.818, P=0.021)是独立危险因素。基于此构建列线图预测模型,预后校准曲线显示模型在1、3和5年复发风险的�Objective To investigate the factors influencing the efficacy of intravesical Bacille Calmette-Guérin(BCG) instillation after transurethral resection of bladder tumor(TURBT) in patients with intermediate-and high-risk non-muscle invasive bladder cancer(NMIBC), and to construct a prediction model for recurrence after BCG treatment. Methods A retrospective cohort study was conducted on the subjected patients diagnosed with intermediate-and high-risk NMIBC undergoing TURBT followed by standard BCG instillation. The 110 patients treated in Department of Urology of Army Medical Center of PLA from January 2018 to December 2023 were assigned into a training set, while the 52 patients treated at Department of Urology of General Hospital of Central Theater Command from January 2015 to December 2020 were into an external validation set. A total of 17 variables were included and analyzed. Univariate and multivariate Cox regression analyses were performed to identify factors associated with recurrence after BCG instillation, and nomograms were plotted to predict 1-year, 3-year, and 5-year recurrence-free survival(RFS). Calibration curve, decision curve analysis(DCA), and receiver operating characteristic(ROC) curve analysis were conducted for internal and external validation to evaluate the predictive performance and clinical utility of the model. Results In the training set, 26 patients(23. 64%) experienced recurrence during the follow-up period, with a median RFS of 32. 00(18. 00~50. 50) months. Univariate Cox regression analysis suggested that platelet count, eosinophil to lymphocyte ratio(ELR), neutrophil to lymphocyte ratio(NLR), platelet to lymphocyte ratio(PLR), systemic immune inflammation(SII) index, and neutrophil-monocyte to lymphocyte ratio(NMLR), pathological T1 stage(pT1) tumor and hemoglobin, albumin, lymphocyte, and platelet(HALP) score were potential factors influencing recurrence after BCG instillation. Multivariate Cox regression analysis identified high HALP score(HR=0. 185, 95%CI: 0. 046~0. 736, P=0. 01

关 键 词：非肌层浸润性膀胱癌 卡介苗 复发 预测模型 

分 类 号：R730.7[医药卫生—肿瘤] R737.14[医药卫生—临床医学] R979.5