南方医科大学学报

南方医科大学学报 ›› 2023, Vol. 43 ›› Issue (3): 488-494.doi: 10.12122/j.issn.1673-4254.2023.03.21

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单中心非肌层浸润性膀胱癌患者行卡介苗灌注治疗的疗效分析

蔡涛浓，卢江丽，林志君，罗明睿，梁海滔，秦自科，叶云林   

  1. 中山大学肿瘤防治中心泌尿外科，华南肿瘤学国家重点实验室，肿瘤医学协同创新中心，广东 广州 510060
  • 出版日期:2023-03-20 发布日期:2023-03-20

Intravesical instillation of bacillus Calmette-Guerin for non-muscle invasive bladder cancer: outcomes of 421 patients in a single center

CAI Taonong, LU Jiangli, LIN Zhijun, LUP Mingrui, LIANG Haitao, QIN Zike, YE Yunlin   

  1. Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; State Key Laboratory of Oncology in South China, Guangzhou 510060, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
  • Online:2023-03-20 Published:2023-03-20

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摘要： 目的 探讨非肌层浸润性膀胱癌（NMIBC）患者行卡介苗（BCG）灌注治疗的疗效、不良反应及其独立危险因素。方法 回顾2015年9月~2021年9月于中山大学肿瘤防治中心术后BCG灌注的患者资料。采用无复发生存率（RFS）、无进展生存率（PFS）和疾病特异生存率（DSS）评估BCG灌注患者的预后。不良反应事件评价标准5.0版评估灌注后不良反应。采用Kaplan-Meier 生存分析，单因素、多因素COX回归分析BCG灌注的独立预测因子。结果 共纳入患者421名，患者平均年龄为61.79±11.51岁，中位随访时间为17月。BCG灌注后88名患者发现复发（20.9%），中位复发时间为13个月；40名患者出现进展（9.5%），中位时间为18个月；14名患者死亡（3.3%），中位时间为30个月。201名患者出现相关不良反应，1级不良反应的患者有69名；2级不良反应有110名；3级不良反应23名。生存分析提示当患者年龄小于67.5岁（P=0.013），肿瘤为初发（P<0.001）、单发（P=0.010）、超过1年复发（P=0.042），且患者中性粒细胞较低（P=0.005），单核细胞较低（P=0.001），NLR（中性粒细胞/淋巴细胞）（P=0.014）较低，细胞角蛋白19片段（CyFra21-1）（P=0.002）较低时无复发生存率明显升高，当患者年龄小于67.5岁（P=0.042），肿瘤为初发（P<0.001），CyFra21-1较低（P=0.042）时患者无进展生存率更高。多因素COX分析提示：肿瘤复发时间（P=0.007，HR=2.669，95% CI 1.316-5.414）、单核细胞数（P=0.015，HR=0.376，95% CI 0.171-0.829）和CyFra21-1值（P=0.002，HR=0.312，95% CI 0.151-0.647）是 NMIBC 患者 BCG 灌注 RFS 的独立预测因素；肿瘤初发或复发（P=0.003，HR=0.301，95% CI 0.138-0.660）、中性粒细胞数（P=0.028，HR=0.302，95% CI 0.103-0.882）和CyFra21-1值（P=0.029，HR=0.358，95% CI 0.142-0.903）是PFS的独立预测因素。结论 对于中、高危的NMIBC患者术后的BCG灌注治疗效果显著，且大部分的不良反应患者可耐受。肿瘤的复发时间、单核细胞计数和CyFra21-1为RFS的独立预测因素，肿瘤的初发或复发、中性粒细胞计数以及CyFra21-1为PFS的独立预测因素。

关键词: 非肌层浸润性膀胱癌；卡介苗；预后；不良反应；独立危险因素

Abstract: Objective To assess the therapeutic effect and adverse effect of intravesical instillation of bacillus Calmette-Guerin (BCG) for treatment of non-muscle invasive bladder cancer (NMIBC) and analyze the independent predictors of patient survival. Methods We retrospectively collected the clinical data from 421 patients (mean age 61.79±11.51 years) with NMIBC, who received intravesical instillation of BCG after surgery in Sun Yat-sen University Cancer Center from September, 2015 to September, 2021. Recurrence-free survival (RFS), progression-free survival (PFS), and disease specific survival (DSS) of the patients were analyzed, and the adverse effects were assessed using Common Terminology Criteria for Adverse Events 5.0. Kaplan-Meier analysis, univariate and multivariate COX regression analyses were used to identify the independent predictors of the patients' survival outcomes. Results The median follow-up of the patients was 17 months, during which 88 (20.9%) patients experienced recurrence (median time to recurrence of 10 months, range 3-58 months); 40 (9.5% ) patients showed tumor progression (median time to progression of 18 months, range 3- 50 months); and 14 (3.3% ) patients died (median survival time of 30 months, range 8-52 months). Adverse events of grade 1, 2, and 3 occurred in 69, 110, and 23 of the patients, respectively. Survival analysis indicated that an age below 67.5 years (P=0.013), first tumor onset (P<0.001), solitary tumor (P=0.010), time to recurrence over one year (P=0.042), low levels of neutrophils (P=0.005), monocytes (P=0.005) and neutrophil/lymphocyte ratio (NLR; P=0.014), and cytokeratin 19 fragment 21-1 (CyFra21-1; P=0.002) were all associated with a higher PFS rate. Multivariate COX analysis suggested that the time of tumor recurrence (P=0.007, HR=2.669, 95% CI: 1.316- 5.414), monocyte counts (P=0.015, HR=0.376, 95%CI: 0.171-0.829), and serum CyFra21-1 level (P=0.002, HR=0.312, 95%CI: 0.151-0.647) were independent predictors of RFS; primary tumor or tumor relapse (P=0.003, HR=0.301, 95% CI: 0.138- 0.660), neutrophil counts (P=0.028, HR=0.302, 95%CI: 0.103-0.882), and CyFra21-1 level (P=0.029, HR=0.358, 95%CI: 0.142-0.903) were independent predictors of PFS following BCG instillation. Conclusion Intravesical instillation of BCG is effective for treatment of intermediate or high-risk NMIBC, and the adverse effects are tolerable in most cases. The time of tumor recurrence, monocyte counts, and serum CyFra21-1 level are independent predictors of RFS, and primary tumor or tumor relapse, neutrophil counts, and CyFra21-1 level are independent predictors of PFS.

Key words: non-muscle invasive bladder cancer; bacillus Calmette-Guerin; prognosis; adverse effect; independent predictor