卡介苗膀胱灌注预防中、高危非肌层浸润性膀胱癌复发的疗效及并发症分析

Efficacy and complications of intravesical instillation of BCG for prevention of recurrence of moderate and high-risk non muscle invasive bladder cancer

目的 探讨卡介苗(BCG)膀胱灌注预防中、高危非肌层浸润性膀胱癌(NMIBC)复发的效果,以及经尿道膀胱肿瘤电切术术后辅助BCG膀胱灌注治疗的并发症发生情况。 方法 回顾性分析2013年12月至2016年10月东北三省18家医院应用BCG膀胱灌注(诱导期持续6周,每周1次,120 mg/次,有或没有维持灌注)治疗的中、高危NMIBC患者的临床、病理资料。研究分为两个部分。第一部分共106例中、高危NMIBC患者,男83例,女23例。平均年龄为66.7岁。初发肿瘤73例(68.9%),复发肿瘤33例(31.1%)。病理分期T1期86例(81.1%),Ta期20例(18.9%);合并原位癌6例(5.7%)。均于经尿道膀胱肿瘤电切术后行辅助BCG膀胱灌注治疗。随访时间≥6个月,观察患者肿瘤复发及进展情况,分析无复发生存时间,采用logistic回归分析影响肿瘤复发的独立危险因素。第二部分在第一部分患者基础上增加了被第一部分研究剔除,但符合BCG治疗标准且接受BCG膀胱灌注治疗的患者,共276例因膀胱肿瘤行经尿道膀胱肿瘤电切术,术后应用BCG膀胱灌注治疗,男211例,女65例。平均年龄68.3岁。中、高危NMIBC 263例,肾盂/输尿管癌术后膀胱内再发中、高危NMIBC 8例,肾盂/输尿管癌同时合并中、高危NMIBC 5例。记录患者BCG灌注过程中停药原因及并发症情况。根据WHO药物毒副作用及分级标准,将BCG膀胱灌注后并发症分为4级。 结果 第1部分106例,中位随访时间12个月。9例(8.5%)出现膀胱肿瘤复发,其中2例(1.9%)出现进展;97例无复发,1年无复发生存率为91.5%。BCG灌注治疗后,73例初发肿瘤者中4例(5.4%)复发,33例复发肿瘤者中5例(15.1%)再次复发。logistic回归分析结果显示肿瘤复发病史(OR=3.214,95%CI0.804~12.845,P=0.099)是患者BCG膀胱灌注治疗后肿瘤再次复发的独立危险因素。第2部分276例,177例(64.1%)发生并发症,其中11例(4.0%)为Ⅲ/Ⅳ级并发症,经过对症及抗结核治疗获得满意效果。36例(13.0%)中途停药,主要原因为:原发疾病复发或进展更换治疗方案12例(4.4%),出现Ⅲ/Ⅳ级并发症11例(4.0%),经济原因9例(3.3 %)。 结论 NMIBC术后应用BCG膀胱灌注治疗可获得较高的1年无复发生存率,灌注相关的Ⅲ/Ⅳ级并发症发生率较低。肿瘤复发病史是影响患者BCG膀胱灌注治疗后肿瘤再次复发的独立危险因素。

Objective To assess the efficacy and side effects of intravesical instillation of BCG after transurethral resection of the bladder tumor (TURBT) in non-muscle invasive bladder cancer (NMIBC) patients.Methods The clinical data of patients treated with BCG 120 mg per course induced perfusion or more after TURBT from December 2013 to October 2016 in 18 hospitals of northeast China region, were analyzed retrospectively. The first part, data of 106 patients with moderate, high-risk NMIBC were collected. A total of 83 patients were male, while the other 23 patients were female. The average age was 66.7 years old.The clinical staging were T1 in 86(81.1%) cases, Ta in 20(18.9%) cases and carcinoma in situ in 6(5.7%)patients. Intravesical instillation of BCG was executed after transurethral resection of the bladder tumor. The incidence rate of recurrence and progression during more than 6 months’ follow-up time were observed. Multivariate analyses were done by using logistic analysis and Cox proportional hazards regression model with Kaplan-Meier method. The second part, treatment compliance of 276 patients with bladder cancer, including moderate/high-risk NMIBC in 263 cases, moderate/high-risk NMIBC followed with renal pelvis/ureteral carcinoma in 8 cases were and moderate/high-risk NMIBC with renal pelvis/ureteral carcinoma in 5 cases who treated with BCG after the surgeries, were observed. Patients consisted of 211 males and 65 females with average age of 68.3 years.Results With a median follow-up of 12 months, 9(8.5%) patients experienced tumor recurrence and 2(1.9%)patients were found progression in the first part. The one-year cancer free recurrence rate of the patients was 91.5%. Statistically significant prognostic factors for recurrence identified by multivariable analyses were prior recurrence of the tumors (OR=3.214, 95%CI 0.804-12.845, P=0.099). In the second port, an incidence rate of adverse effects was 64.1% (177/276). The Ⅲ/Ⅳ degree complications were occurred in 11 patients and satisfactory outcomes achieved with active treatment. A total of 36 patients withdrawal with the major causes were recurrence and progression of bladder tumor in 12 cases (4.4 %), 9 cases (3.3 %) with economic reasons and 11 cases(4.0%)with serious complications.Conclusions NMIBC patients treated with intravesical BCG therapy have approving cancer free recurrence rates and acceptable adverse effects. Prior recurrence may be prognostic factor of recurrence after intravesical BCG therapy.