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. 2017 Sep;198(3):503-510.
doi: 10.1016/j.juro.2017.01.086. Epub 2017 Mar 10.

Efficacy of bacillus Calmette-Guérin Strains for Treatment of Nonmuscle Invasive Bladder Cancer: A Systematic Review and Network Meta-Analysis

Brock E Boehm  1 , John E Cornell  1 , Hanzhang Wang  1 , Neelam Mukherjee  1 , Jacob S Oppenheimer  1 , Robert S Svatek  2
Affiliations

Efficacy of bacillus Calmette-Guérin Strains for Treatment of Nonmuscle Invasive Bladder Cancer: A Systematic Review and Network Meta-Analysis

Brock E Boehm et al. J Urol. 2017 Sep.

Abstract

Purpose: We sought to determine the efficacy of genetically distinct bacillus Calmette-Guérin strains in preventing disease recurrence in patients with nonmuscle invasive bladder cancer.

Materials and methods: We conducted a systematic review and network meta-analysis of trials evaluating bacillus Calmette-Guérin strains against all possible comparators (different bacillus Calmette-Guérin strains, chemotherapy and nonbacillus Calmette-Guérin biological therapies) with intravesical chemotherapy as the common comparator. MEDLINE® (http://www.ncbi.nlm.nih.gov/pubmed) served as the primary data source, with the search from inception to October 2016 for clinical trials involving patients with nonmuscle invasive bladder cancer receiving bacillus Calmette-Guérin. Primary outcome measure was bladder cancer recurrence, defined as recurrent bladder tumor of any grade or stage. Random effect network meta-analysis provided estimates for outcomes and is presented as odds ratios.

Results: Across all possible comparators (65 trials, 12,246 patients, 9 strains) there were 2,177 recurrences in 5,642 treated patients (38.6%) and 2,316 recurrences in 5,441 comparators (42.6%). With chemotherapy as the common comparator (28 trials, 5,757 patients, 5 strains) Tokyo-172 (OR 0.39, 95% CI 0.16-0.93), Pasteur (OR 0.49, 95% CI 0.28-0.86) and TICE® (OR 0.61, 95% CI 0.40-0.93) strains were significantly better than chemotherapy at preventing recurrence. No bacillus Calmette-Guérin strain demonstrated significant superiority when compared to any other strain at preventing recurrence in the network meta-analysis.

Conclusions: Bacillus Calmette-Guérin strains exhibited significant differences in efficacy compared to chemotherapy. However, no definitive conclusions could be reached regarding strain superiority, and head-to-head trials are greatly needed to further understand the importance of strain selection in determining bacillus Calmette-Guérin efficacy.

Keywords: BCG vaccine; immunotherapy; urinary bladder neoplasms.

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Conflict of interest statement

The authors declare no potential conflicts of interest

Figures

Figure 1.
Figure 1.
Flowchart Detailing Inclusion of Trials
Figure 2.
Figure 2.
Risk of Bias Graph
Figure 3.
Figure 3.
Impact of individual treatments on disease relapse of direct pairwise meta-analysis.
Figure 4.
Figure 4.. Network Maps.
Network maps were created for bladder cancer recurrence based upon (a) all possible comparators and (b) chemotherapy as common comparator. The size of the nodes (blue circles) corresponds to the number of trials using each treatment. Each treatment is linked with a black line, the thickness of which corresponds to the number of trials that evaluated the treatments. Induct = BCG Induction only. LOW = low-dose BCG. Surgery = TURBT. AF = Armand-Frappier. BCG-Chemo = Combination BCG and chemotherapy. Chemo = chemotherapy.
See this image and copyright information in PMC

References

    1. Siegel RL, Miller KD, Jemal A: Cancer statistics, 2016. CA Cancer J Clin, 66: 7, 2016 - PubMed
    1. Association., A. U.: Guidelines for the Management of Non-Muscle Invasive Bladder Cancer (Stages Ta, T1, and TIS): 2007 Update. Linthicum, MD, Updated 2007
    1. Gan C, Mostafid H, Khan MS et al.: BCG immunotherapy for bladder cancer--the effects of substrain differences. Nat Rev Urol, 10: 580, 2013 - PubMed
    1. Ritz N, Hanekom WA, Robins-Browne R et al.: Influence of BCG vaccine strain on the immune response and protection against tuberculosis. FEMS Microbiol Rev, 32: 821, 2008 - PubMed
    1. Fellows GJ, Parmar MK, Grigor KM et al.: Marker tumour response to Evans and Pasteur bacille Calmette-Guerin in multiple recurrent pTa/pT1 bladder tumours: report from the Medical Research Council Subgroup on Superficial Bladder Cancer (Urological Cancer Working Party). Br J Urol, 73: 639, 1994 - PubMed

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