title: Low-Dose Versus Standard Dose of Bacillus Calmette-Guerin in the Treatment of Nonmuscle Invasive Bladder Cancer: A Systematic Review and Meta-Analysis.
abstract: 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/).
authors.affiliation: 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.
authors.forename: Shuxiong
authors.initials: S
authors.lastname: Zeng
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Yu
authors.forename: Chong
authors.initials: C
authors.lastname: Ma
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Ruixiang
authors.initials: R
authors.lastname: Song
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Yinghao
authors.initials: Y
authors.lastname: Sun
authors.forename: Chuanliang
authors.initials: C
authors.lastname: Xu
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001500:BCG Vaccine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D009364:Neoplasm Recurrence, Local; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine