Determining optimal maintenance schedules for adjuvant intravesical bacillus Calmette–Guerin immunotherapy in non-muscle-invasive bladder cancer: a systematic review and network meta-analysis

Abstract

Objectives: To figure out optimal bacillus Calmette–Guerin (BCG) maintenance schedules for non-muscle-invasive bladder cancer (NMIBC) patients by comparing different schedules in a systematic review using conventional and network meta-analysis.

Materials and methods: Literature was searched in the databases of Medline, Embase, Cochrane library, Clinicaltrials.gov, Wanfang, CNKI and SinoMed in April 2016 and 9 randomized clinical trials comparing intravesical BCG maintenance therapy with BCG induction-only therapy or comparing different BCG maintenance schedules (induction-only, 1 year, 1.5 year, 2 year, 3 year maintenance) in NMIBC patients were included. Conventional and network meta-analyses within a Bayesian framework were performed to calculate odds ratios of tumor recurrence, progression and side effects (cystitis, hematuria, general malaise and fever). The surface under the cumulative ranking curve (SUCRA) mean ranking was used to obtain schedule hierarchy.

Results: Data from 1951 patients showed that longer-term maintenance BCG therapy does not significantly decrease tumor recurrence and progression rate of NMIBC compared to shorter-term maintenance BCG therapy. However, longer-maintenance therapy does not increase side effect incidence compared to induction-only therapy. According to SUCRA results, induction-only therapy has the highest probability of recurrence and progression but least probability of side effects.

Conclusions: Longer BCG maintenance therapy (such as 3 years) is not superior to shorter maintenance therapy (such as 1 year). But maintenance therapy overall is better than induction-only BCG therapy while not increasing side effects. Though further evidence and clinical practice with balanced confounding factors (risk stratification and BCG strain) are wished for, the current study suggests the common use of 1 year intravesical BCG instillation for NMIBC patients.

Keywords:

• Intravesical bacillus Calmette–Guerin
• non-muscle-invasive bladder cancer
• maintenance
• efficacy
• side effects

Transparency

Declaration of funding

This study was not funded.

Author contributions: The study was designed by Z.H. and Y.W. They also reviewed the included studies and extracted data. When disagreement existed, H.L., C.Z. and T.X. were referred to for verification. Z.H. and H.L. evaluated the RCT quality and researched the data. While Z.H. wrote the paper, H.L. and T.X. contributed to interpreting the results, draft reviewing, and finalizing the paper. All the authors have read and approved the final version.

Declaration of financial/other relationships

Z.H., H.L., Y.W., C.Z. and T.X. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

We gratefully acknowledge the kind cooperation of Dr. Yiqing Du in the preparation of this research.