Different Chemotherapy Regimens in the Management of Advanced or Metastatic Urothelial Cancer: a Bayesian Network Meta-Analysis of Randomized Controlled Trials.

Background/aims: Urothelial cancer (UC) as a chemotherapy-sensitive tumor, has achieved remarkable progresses in therapeutic paradigm, particularly in the advanced/metastatic stages. However, both clinicians and patients are confused when it comes to choosing the optimal chemotherapy. Hence, this article was aimed to conduct a comprehensive comparison of different chemotherapy regimens for advanced or metastatic UC in terms of survival benefits or adverse events.

Methods: The online databases PubMed, EMBASE and Web of Science were searched systematically and comprehensively for randomized controlled trials (RCTs) up to September 15, 2017. The pooled hazard ratios (HRs) or odds ratios (ORs) with 95% credible interval (CrI) were calculated by Markov chain Monte Carlo methods. The effectiveness and safety of included regimens were conducted to provide a hierarchy by means of rank probabilities with the help of "R-3.4.0" software and the "gemtc-0.8.2" package. The surface under the cumulative ranking curve (SUCRA) was also incorporated in our analysis for ranking the corresponding chemotherapy regimens.

Results: Ten different chemotherapy regimens involved in this article were predominantly of trials in a first-line setting, and eight clinical outcomes were ultimately analyzed in this study. In terms of Overall response rate (ORR), Overall survival (OS) or Progression-free survival (PFS)/Time to progression (TTP), the rank probabilities and SUCRA indicated that Paclitaxel/cisplatin/gemcitabine (PCG) was superior to gemcitabine/cisplatin (GC) or methotrexate/vinblastine/doxorubicin/cisplatin (MVAC), the traditional first-line treatment for advanced/metastatic UC. In the case of ORR or PFS/TTP, GC+sorafenib also displayed its superiority in comparison with GC or MVAC. Despite their survival benefits, PCG or GC+sorafenib presented a relatively higher incidence of adverse events.

Conclusion: Our results revealed that by adding a paclitaxel or sorafenib into the first-line GC, it could yield a better survival benefit, but also worsen adverse events for advanced/ metastatic UC. Clinically, physicians should weigh the merits of these approaches to maximize the survival benefits of eligible patients.