Adjuvant chemotherapy for muscle-invasive bladder cancer: a systematic review and network meta-analysis of randomized clinical trials

Hyung Suk Kim, Chang Wook Jeong, Cheol Kwak, Hyeon Hoe Kim and Ja Hyeon Ku _

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Oncotarget. 2017; 8:81204-81214. https://doi.org/10.18632/oncotarget.20979

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Hyung Suk Kim1, Chang Wook Jeong2, Cheol Kwak2, Hyeon Hoe Kim2 and Ja Hyeon Ku2

1Department of Urology, Dongguk University Ilsan Medical Center, Goyang, Korea

2Department of Urology, Seoul National University Hospital, Seoul, Korea

Correspondence to:

Ja Hyeon Ku, email: [email protected]

Keywords: bladder cancer, muscle-invasive, chemotherapy, cystectomy, systematic review

Received: May 31, 2017     Accepted: August 28, 2017     Published: September 18, 2017


Although adjuvant chemotherapy (ACH) is widely used in clinical practice for the management of muscle-invasive bladder cancer (MIBC), a consensus has yet to be established on which ACH regimen is the most effective for improving postoperative survival. In this study, we aimed to systematically assess the optimal ACH regimen for improving survival outcomes in patients treated with radical cystectomy (RC) for MIBC. A comprehensive literature search was conducted in the PubMed, Embase, and the Cochrane Library databases for all articles published until December 2016 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The study end-points were progression-free survival (PFS) and overall survival (OS). A direct pairwise meta-analysis was conducted by pooling the studies that compared RC with ACH and RC alone, and the results are presented as a pooled hazard ratio (HR) with a 95% confidence interval (CI). A Bayesian network meta-analysis was adopted for indirect comparisons among various ACH regimens, and the outcomes are presented as HRs with 95% credible intervals (CrI). The eleven randomized controlled trials ultimately selected for the current analysis comprised of 1,546 patients with 49 to 327 subjects per study. Based on the pairwise meta-analysis, the use of ACH showed significantly better PFS (HR, 0.64; 95% CI, 0.49–0.85) and OS (HR, 0.79; 95% CI, 0.68–0.92) than RC alone. In the network meta-analysis, the gemcitabine/cisplatin/paclitaxel (GCP) combination was the only ACH regimen associated with significant improvement in both the PFS (HR, 0.38; 95% CrI, 0.25–0.58) and OS (HR, 0.38; 95% CrI 0.22–0.65). ACH following RC for MIBC may therefore contribute to improved PFS and OS. In particular, the GCP combination may be the optimal ACH regimen for improving postoperative survival outcomes. Additional well-designed, large scale, prospective, randomized trials are still required to establish the optimal ACH regimen in MIBC patients.

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