Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: A Systematic Review and Two-Step Meta-Analysis

Abstract

Background: Platinum-based neoadjuvant chemotherapy has been shown to improve survival outcomes in muscle-invasive bladder cancer patients. We performed a systematic review and meta-analysis to provide updated results of previous findings. We also summarized published data to compare clinical outcomes of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) versus gemcitabine and cisplatin/carboplatin (GC) in the neoadjuvant setting.

Methods: A meta-analysis of 15 randomized clinical trials was performed to compare neoadjuvant chemotherapy plus local treatment with the same local treatment alone. Because no randomized trials have investigated MVAC versus GC in the neoadjuvant setting, a meta-analysis of 13 retrospective studies was performed to compare MVAC with GC.

Results: A total of 3,285 patients were included in 15 randomized clinical trials. There was a significant overall survival (OS) benefit associated with cisplatin-based neoadjuvant chemotherapy (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.79-0.96). A total of 1,766 patients were included in 13 retrospective studies. There was no significant difference in pathological complete response between MVAC and GC. However, GC was associated with a significantly reduced overall survival (HR, 1.26; 95% CI, 1.01-1.57). After excluding carboplatin data, GC still seemed to be inferior to MVAC in OS (HR, 1.31; 95% CI, 0.99-1.74), but the difference was no longer statistically significant.

Conclusion: These results support the use of cisplatin-based combination neoadjuvant chemotherapy in muscle-invasive bladder cancer. Although GC and MVAC had similar treatment response rates, the different survival outcome observed in this study requires further investigation.

Implications for practice: Platinum-based neoadjuvant chemotherapy (NCT) has been shown to improve survival outcomes in muscle-invasive bladder cancer (MIBC) patients, but the optimal neoadjuvant regimen has not been established. Methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and gemcitabine and cisplatin/carboplatin (GC) are two of the most commonly used chemotherapy regimens in modern oncology. In this two-step meta-analysis, an updated and more precise estimate of the survival benefit of cisplatin-based NCT in MIBC is provided. This study also demonstrated that MVAC might have superior overall survival compared with GC (with or without carboplatin data) in the neoadjuvant setting. The findings suggest that NCT should be standard care in MIBC, and MVAC could be the preferred neoadjuvant regimen.

Keywords: Bladder cancer; Chemotherapy; Neoadjuvant; Platinum; Survival.

Figure 1.

Flowchart for article selection. Only randomized trials were included to compare NCT plus locoregional therapy versus locoregional therapy, whereas retrospective studies were included to compare GC versus MVAC because no randomized trials were available. Abbreviations: GC, gemcitabine and cisplatin/carboplatin; MVAC, methotrexate, vinblastine, doxorubicin, and cisplatin; NCT, neoadjuvant chemotherapy.

Figure 2.

Forest plot of overall survival in comparison of cisplatin-based neoadjuvant chemotherapy plus locoregional therapy versus locoregional therapy alone by randomized clinical trials. Abbreviations: CI, confidence interval; IV, inverse variance; NCT, neoadjuvant chemotherapy.

Figure 3.

Forest plot of pathological complete response in comparison of GC versus MVAC by retrospective studies. Abbreviations: CI, confidence interval; GC, gemcitabine and cisplatin/carboplatin; M-H, Mantel-Haenszel method; MVAC, methotrexate, vinblastine, doxorubicin, and cisplatin; NCT, neoadjuvant chemotherapy.

Figure 4.

Forest plot of overall survival in comparison of GC versus MVAC by retrospective studies. Abbreviations: CI, confidence interval; GC, gemcitabine and cisplatin/carboplatin; IV, inverse variance; MVAC, methotrexate, vinblastine, doxorubicin, and cisplatin.