Combination of Intravesical Chemotherapy and Bacillus Calmette–Guerin Versus Bacillus Calmette–Guerin Monotherapy in Intermediate- and High-risk Nonmuscle Invasive Bladder Cancer

Abstract

Urothelial carcinoma of the bladder has become a major cause of morbidity, mortality, and health-related costs. There is still no standard instillation therapy against bladder cancer. A meta-analysis was conducted to evaluate the efficacy and toxicity of adding chemotherapy to Bacillus Calmette–Guerin (BCG) in intermediate- and high-risk nonmuscle invasive bladder cancer (NMIBC).All randomized controlled trials (RCTs) that evaluated the efficacy of combination therapy and BCG monotherapy for intermediate- and high-risk NMIBC were comprehensively searched. Relevant databases, including PubMed, Embase, Cochrane Central Register of Controlled trials databases, and American Society of Clinical Oncology (http://www.asco.org/ASCO), the clinical trial registration website (ClinicalTrials.gov), and relevant trials from the references of selected studies were searched from initial state up to June 6, 2015. Random-effects model was used to estimate hazard ratios (HRs) statistics. All statistical analyses were performed by STATA (version 13.0, College Station, TX).Seven studies, including 1373 patients with intermediate- and high-risk NMIBC, were identified. For disease-free survival, the pooled HRs from all studies was 0.69 (95% confidence interval [CI], 0.48–1.00; P = 0.048). The disease-free survival benefit was more apparent among patients with intermediate-risk NMIBC (P = 0.002) or Ta/T1 with/without carcinoma in situ (P < 0.01). In subgroup analysis, a significant reduction in recurrence was found in studies that explored the influence of a perioperative single dose instillation compared with delayed BCG monotherapy (HR = 0.60; 95% CI, 0.38–0.92; P = 0.021). No significant difference was found for progression-free survival (HR = 0.78; 95% CI, 0.43–1.44; P = 0.435).Patients with intermediate- and high-risk NMIBC who underwent combination therapy achieved lower rates of recurrence than those who underwent BCG therapy alone. No difference in progression-free survival was found between the 2 different therapy schedules. Better efficacy for a perioperative single dose instillation compared with delayed BCG monotherapy was found in this meta-analysis.

New onset of myasthenia gravis after intravesical Bacillus Calmette-Guerin

“…Intravesical BCG is used to prevent the recurrence and progression of nonmuscle invasive bladder cancer after the TUR procedure. [ 9 ] First described by Morales et al [ 10 ] in 1976, intravesical BCG after TUR is known to provide a significant advantage over TUR alone in delaying tumor recurrence in patients with medium/high-risk Ta or T1 bladder cancer. [ 11 ] The immune response triggered by BCG to the bladder urothelium activates proinflammatory cytokines and promotes neutrophils, monocytes/macrophages, lymphocytes, natural killer cells, and dendritic cells.…”

Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of bladder carcinoma

“…Multiple clinical trials and a meta-analysis have produced conflicting results regarding the success of treatments using BCG with intravesical interferon-alpha versus BCG alone [ 10 – 16 , 39 , 40 ]. Interferon-alpha has been combined with BCG in several studies and the role of this combination continues to be evaluated.…”

Primary urothelial carcinoma of the prostate

“…Several reports have found that complete resection of the visible tumor and intravesical instillation of Bacillus Calmette-Guérin (BCG) is the preferred treatment for carcinoma in situ (CIS) in the prostatic urethral mucosa. [16–18] Treatment of urothelial carcinoma invading the prostatic ducts is still a controversial issue. Many scholars advocate radical surgery in patients with ductal invasion, [19,20] whereas Palou Redorta et al reported that patients with CIS involving the prostatic ducts could be treated with intravesical BCG, which has a 70% complete response rate.…”