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

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

doi:10.18632/oncotarget.20979

Abstract

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.

Highlights

Muscle-invasive bladder cancer (MIBC), which accounts for 20% to 30% of all bladder cancers at the initial diagnosis, is primarily treated with radical cystectomy (RC) combined with bilateral pelvic lymph node dissection (PLND) [1]
These findings suggest that RC alone may be insufficient to completely control the disease and that the additional use of systemic therapy should be considered in the majority of patients with locally advanced muscle-invasive bladder cancer (MIBC)
We aimed to evaluate the efficacy of adjuvant chemotherapy (ACH) and determine the optimal ACH regimen associated with significant improvement in survival outcomes in MIBC patients who underwent RC

Summary

Introduction

Muscle-invasive bladder cancer (MIBC), which accounts for 20% to 30% of all bladder cancers at the initial diagnosis, is primarily treated with radical cystectomy (RC) combined with bilateral pelvic lymph node dissection (PLND) [1]. In cases of locally advanced MIBC, including pT3–4 tumor or lymph node positive (N+) disease, the 5-year RFS and overall www.impactjournals.com/oncotarget survival (OS) rates after RC are 35 to 60% and 25% to 50%, respectively [1, 2]. Distant recurrence of bladder cancer is more frequent than locoregional recurrence [1, 4]

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