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. 2019 Mar 1:9:121.
doi: 10.3389/fonc.2019.00121. eCollection 2019.

Combination of Intravesical Bacille Calmette-Guérin and Chemotherapy vs. Bacille Calmette-Guérin Alone in Non-muscle Invasive Bladder Cancer: A Meta-Analysis

Di Huang  1 , Ying-Hui Jin  1 , Hong Weng  1   2 , Qiao Huang  1 , Xian-Tao Zeng  1   2 , Xing-Huan Wang  1   2
Affiliations

Combination of Intravesical Bacille Calmette-Guérin and Chemotherapy vs. Bacille Calmette-Guérin Alone in Non-muscle Invasive Bladder Cancer: A Meta-Analysis

Di Huang et al. Front Oncol. .

Abstract

Background: About 75% of newly diagnosed bladder cancer cases suffer from non-muscle invasive bladder cancer (NMIBC), which used to recur and progress despite transurethral resection of bladder tumor (TURBT). This meta-analysis was conducted to examine if combined application of intravesical bacille Calmette-Guérin (BCG) with chemotherapy is associated with better prognosis. Methods: Systematic searches of randomized controlled trials (RCTs) concerning NMIBC were performed in PubMed, EMbase, CENTRAL, CNKI, WanFang, VIP, CBM databases, and some specialized websites. Two researchers independently implemented study selection, quality assessment and data extraction. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for treatment effects on recurrence-free survival (RFS), progression-free survival (PFS), overall survival (OS) and disease-specific survival (DSS) were directly extracted, if available, or estimated using relevant data from included studies. Side effects, such as fever, gastrointestinal reaction, cystitis, irritative bladder symptoms and hematuria, were also extracted as outcome measurements, and associated relative risks (RRs) were calculated to assess treatment safety. RevMan 5.3 software was used to perform statistical analyses. Results: Thirteen RCTs containing 1,754 patients with NMIBC were included in this meta-analysis. Compared with BCG alone, the combination therapy significantly improved RFS (HR = 0.53, 95% CI: 0.43-0.66, P < 0.01), OS (HR = 0.66, 95%CI: 0.50-0.86, P = 0.002), and DSS (HR = 0.48, 95%CI: 0.29-0.80, P = 0.005). While PFS showed no obvious difference between combination therapy and BCG alone (HR = 0.65, 95%CI: 0.25-1.68, P = 0.38). The rate of fever (RR = 0.50, 95%CI: 0.27-0.91, P = 0.02), irritative bladder symptoms (RR = 0.69, 95%CI: 0.52-0.90, P = 0.007) and hematuria (RR = 0.50, 95%CI: 0.28-0.89, P = 0.02) were significantly decreased in patients treated with combination therapy compared to those with BCG alone. There were no statistically significant differences between combination therapy and BCG alone in toxicity (RR = 0.69, 95%CI: 0.34-1.40, P = 0.30), gastrointestinal reaction (RR = 2.54, 95%CI: 0.61-10.60, P = 0.20) or cystitis (RR = 0.67, 95%CI: 0.29-1.54, P = 0.34). Conclusions: Combined application of intravesical BCG and chemotherapy appears to be an effective treatment for patients with intermediate- to high-risk NMIBC, but not for those with tumor in situ alone or recurrent bladder cancer.

Keywords: bacille Calmette-Guérin; chemotherapy; meta-analysis; non-muscle invasive bladder cancer; prognosis.

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Figures

Figure 1
Figure 1
Flow diagram of study selection in the meta-analysis.
Figure 2
Figure 2
Risk of bias assessment of included studies.
Figure 3
Figure 3
Forest plot of RFS comparing combination therapy with BCG alone.
Figure 4
Figure 4
Comparison on RFS between combination therapy and BCG alone after subgroup analysis stratified by chemotherapeutic agent used in combination therapy.
Figure 5
Figure 5
Comparison on RFS between combination therapy and BCG alone after subgroup analysis stratified by treatment duration.
Figure 6
Figure 6
Comparison on RFS between combination therapy and BCG alone after subgroup analysis stratified by pathological risk of patients.
Figure 7
Figure 7
Comparison on RFS between combination therapy and BCG alone in patients with high-risk NMIBC.
Figure 8
Figure 8
Forest plot of PFS comparing combination therapy with BCG alone.
Figure 9
Figure 9
Forest plot of OS comparing combination therapy with BCG alone.
Figure 10
Figure 10
Forest plot of DSS comparing combination therapy with BCG.
Figure 11
Figure 11
Forest plot comparing fever between combination therapy and BCG alone.
Figure 12
Figure 12
Forest plot comparing irritative bladder symptoms between combination therapy and BCG alone.
Figure 13
Figure 13
Forest plot comparing hematuria between combination therapy and BCG alone.
Figure 14
Figure 14
Forest plot comparing toxicity between combination therapy and BCG alone after subgroup analysis stratified by treatment duration.
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