中、高危非肌层浸润性膀胱癌卡介苗灌注的疗效与不良反应分析

目的 探究非肌层浸润型膀胱癌(non-muscle-invasive bladder cancer, NMIBC)患者卡介苗（Bacillus Calmette-Guerin，BCG）膀胱灌注治疗的疗效，预后因素以及不良反应。方法 回顾性的分析2014年4月至2021年4月长海医院收治的149名接受BCG灌注的中、高危NMIBC患者的临床数据。随访时间中位数为25个月（4~85个月），其中男性130例（87.2%），女性19例（12.8%）。平均年龄（66.6±10.6）岁。所有患者均行经尿道膀胱肿瘤切除术（transurethral resection of bladder tumor，TURBT），术后进行规律BCG膀胱灌注。采用累计复发率、累计进展率、1年无复发生存率、平均无复发及平均无进展生存时间评估BCG灌注治疗的疗效，单因素和多因素Cox生存分析探究危险因素，不良反应事件评价标准5.0版（Common Terminology Criteria for Adverse Events Vesion5.0, CTCAE Vesion5.0）评估不良反应情况。结果 1年无复发生存率80.8%（105/130）、累计复发率22.1%（33/149），平均无复发生存时间49.64（45.18-54.11）个月；累计进展率9.40%（14/149）、平均无进展生存时间48.95（44.23-53.67）个月。单因素分析结果表明膀胱癌复发病史（P=0.003）和临床分期（P=0.058）与灌注预后相关。多因素Cox回归分析结果显示膀胱癌复发病史（P=0.003，HR=3.50）是BCG灌注后肿瘤复发的独立预测因素。86.8%（112/129）的患者出现不良反应，其中1级不良反应38例（29.5%），2级不良反应71例（55.0%），3级不良反应3例（2.3%），无4及5级不良反应。17例无任何不良反应，8.05%（12/149）的患者因不耐受不良反应而中断治疗。结论 中、高危NMIBC患者TURBT术后BCG膀胱灌注治疗效果显著，膀胱癌复发病史是中、高危NMIBC患者BCG灌注后肿瘤复发的独立危险因素。BCG膀胱灌注存在一定不良反应，但大部分不良反应等级较低，患者可耐受。

Efficacy and adverse reactions of BCG instillation in moderate and high risk non-muscular invasive bladder cancer

Objective To investigate the efficacy, prognostic factors and adverse reactions of intravesical instillation with Bacillus Calmette-Guerin (BCG) in patients with non-muscle-invasive bladder cancer (NMIBC). Methods The clinical data of 149 patients with moderate and high risk NMIBC who received BCG instillation in Changhai Hospital from April 2014 to April 2021 were retrospectively analyzed. The median follow-up time was 25 months (4-85 months). There were 130 males (87.2%) and 19 females (12.8%) among 149 patients. The average age was (66.6±10.6) years. The patients all received intravesical instillation with BCG after transurethral resection of bladder tumor (TURBT). Cumulative recurrence rate, cumulative progression rate, 1-year relapse-free survival rate, mean relapse-free and mean progression-free survival time were used to evaluate the efficacy of BCG, univariate and multivariate Cox survival analysis were used to explore the recurrence-related risk factors, and Common Terminology Criteria for Adverse Events Vesion5.0 (CTCAE Vesion5.0) was used to evaluate adverse reactions. Results The 1-year recurrence free survival rate was 80.8% (105/130), the cumulative recurrence rate was 22.1% (33/149), and the mean recurrence free survival time was 49.64 (45.18-54.11) months. The cumulative progression rate was 9.40% (14/149), and the mean progression-free survival time was 48.95 (44.23-53.67) months. Univariate analysis showed that the history of recurrence (P=0.003) and clinical stage (P=0.058) of bladder cancer were correlated with the recurrence of cancer. Multivariate Cox regression analysis showed that the history of bladder cancer recurrence (P=0.003, HR=3.50) was an independent predictor of cancer recurrence. Adverse reactions occurred in 86.8% (112/129) patients, in which 38 (29.5%) were grade 1 adverse reactions, 71 (55.0%) and 3 (2.3%) were grade 2 and grade 3 respectively. There were no grade 4 and 5 adverse reactions. And there were 17 patients without any adverse reactions. 8.05% (12/149) patients discontinued treatment due to intolerance of adverse reactions. Conclusion Intravesical instillation with BCG after TURBT is effective in patients with moderate and high risk of NMIBC. History of bladder cancer recurrence is an independent risk factor for cancer recurrence after BCG instillation in patients with middle and high risk of NMIBC. BCG instillation has some adverse reactions, but most of the adverse reactions are of low grade and can be tolerated by patients.