Zeng Shuxiong, Yu Xiaowen, Ma Chong, Zhang Zhensheng, Song Ruixiang, Chen Xin, Sun Yinghao, Xu Chuanliang
From the Department of Urology(SZ, CM, ZZ, RS, XC, YS, CX); and Department of Geriatrics(XY), Changhai Hospital, Second Military Medical University, Shanghai, P.R. China.
Medicine (Baltimore). 2015 Dec;94(49):e2176. doi: 10.1097/MD.0000000000002176.
Whether low-dose Bacillus Calmette-Guerin (BCG) treatment can reduce the side effects while maintaining efficacy for patients with nonmuscle invasive bladder cancer (NMIBC) is controversial.To investigate whether low-dose BCG treatment can reduce the side effects while maintaining efficacy for patients with NMIBC when compared with standard-dose BCG treatment.A comprehensive literature search of PubMed, EMBASE, CINAHL, LILACS, and CENTRAL databases was conducted to identify relevant randomized controlled trials (RCT) or quasi-randomized controlled trials (qRCT) that have assessed the efficacy of low- and standard-dose BCG therapy for patients with NMIBC. Systematic review and meta-analysis were performed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis Criteria.Six RCTs and 2 qRCTs were eligible for meta-analysis. Low-dose BCG instillation was not inferior to reduce the risk of bladder tumor recurrence (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.00-1.31; P = 0.05), meanwhile no difference was found regarding tumor progression (HR = 1.08; 95%CI, 0.83-1.42; P = 0.57). However, low-dose BCG provided a significantly lower incidence of overall side effects (RR = 0.75; 95%CI, 0.60-0.94; P = 0.01), systemic side effects (RR = 0.57; 95%CI, 0.34-0.97; P = 0.04), severe side effects (RR = 0.52; 95%CI, 0.36-0.74; P = 0.0003), and withdrawal due to BCG toxicity (RR = 0.49; 95%CI, 0.26-0.91; P = 0.02). In contrast, local side effects were comparable between low- and standard-dose arms (RR = 0.89; 95%CI, 0.73-1.08; P = 0.24).Low-dose BCG instillation significantly reduces the incidence of overall side effects, especially severe and systemic symptoms in patients with NMIBC, while the oncological control efficacy of low-dose BCG is not inferior to standard-dose BCG. Further studies with stratification using different risk factors at randomization are required to assess whether the efficacy of low-dose BCG is comparable to standard dose BCG for different risk of patients.PROSPERO registration No CRD42014014871 (http://www.crd.york.ac.uk/prospero/).
低剂量卡介苗（BCG）治疗在维持非肌层浸润性膀胱癌（NMIBC）患者疗效的同时能否降低副作用存在争议。为了研究与标准剂量BCG治疗相比，低剂量BCG治疗在维持NMIBC患者疗效的同时能否降低副作用。对PubMed、EMBASE、CINAHL、LILACS和CENTRAL数据库进行了全面的文献检索，以确定评估低剂量和标准剂量BCG治疗NMIBC患者疗效的相关随机对照试验（RCT）或半随机对照试验（qRCT）。根据系统评价和Meta分析的首选报告项目标准进行系统评价和Meta分析。六项RCT和两项qRCT符合Meta分析的条件。低剂量BCG灌注在降低膀胱肿瘤复发风险方面并不逊色（风险比[HR]，1.15；95%置信区间[CI]，1.00 - 1.31；P = 0.05），同时在肿瘤进展方面未发现差异（HR = 1.08；95%CI，0.83 - 1.42；P = 0.57）。然而，低剂量BCG的总体副作用发生率显著较低（RR = 0.75；95%CI，0.60 - 0.94；P = 0.01），全身副作用（RR = 0.57；95%CI，0.34 - 0.97；P = 0.04），严重副作用（RR = 0.52；95%CI，0.36 - 0.74；P = 0.0003），以及因BCG毒性导致的停药率（RR = 0.49；95%CI，0.26 - 0.91；P = 0.02）。相比之下，低剂量组和标准剂量组的局部副作用相当（RR = 0.89；95%CI，0.73 - 1.08；P = 0.24）。低剂量BCG灌注显著降低了NMIBC患者的总体副作用发生率，尤其是严重和全身症状，而低剂量BCG的肿瘤学控制疗效不低于标准剂量BCG。需要进一步进行随机分层研究，以评估低剂量BCG对不同风险患者的疗效是否与标准剂量BCG相当。PROSPERO注册号CRD42014014871（http://www.crd.york.ac.uk/prospero/）
