Comparison of Oncologic Outcomes of Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin (ddMVAC) with Gemcitabine and Cisplatin (GC) as Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: Systematic Review and Meta-Analysis

Abstract

Platinum-based neoadjuvant chemotherapy (NAC) is widely used for treating muscle-invasive bladder cancer (MIBC). A systematic review was performed following PRISMA guidelines. PubMed, Embase, and the Cochrane Library were searched up to December 2020. We conducted a meta-analysis to compare the oncologic outcomes of ddMVAC (dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin) and GC (gemcitabine and cisplatin), which are the most widely used NAC regimens. Endpoints included pathologic complete response (pCR), pathologic downstaging (pDS), overall survival (OS), and cancer-specific survival (CSS). Five studies, with a total of 1206 patients, were included for meta-analysis. pCR was observed in 35.2% of the ddMVAC arm and in 25.1% of the GC arm, and pCR was significantly higher in ddMVAC than in GC (odds ratio (OR), 1.45; 95% confidence interval (CI), 1.11–1.89; p = 0.006). There was no significant difference in pDS (OR, 1.37; CI, 0.84–2.21; p = 0.20). OS was significantly higher in ddMVAC than in GC (hazard ratio, 2.16; CI, 1.42–3.29; p = 0.0004). Only one study reported CSS outcomes. The results of this analysis indicate that ddMVAC is superior to GC in terms of pCR and OS, suggesting that ddMVAC is more effective than GC in NAC for MIBC. However, this should be interpreted with caution because of the inherent limitations of retrospective studies.

Tumor-Associated Mast Cells in Urothelial Bladder Cancer: Optimizing Immuno-Oncology

“…At presentation, about 70% of patients with UBC present with disease confined to the mucosa (stage Ta or carcinoma in situ) or submucosa (stage T1) (non–muscle-invasive bladder cancer, NMIBC), which has a good prognosis [ 1 , 2 , 3 , 4 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. NMIBC includes a diverse spectrum of diseases with a wide range of progression and recurrence rates that depend on several clinical and pathologic factors; thus, the key to improving the prognosis of NMIBC is to reduce the risk of recurrence and progression [ 3 , 4 , 7 , 9 , 11 ].…”

“…By contrast, approximately 25% of bladder cancers invade the muscle layers, and 5% have metastatic disease [ 1 , 2 , 4 , 5 , 8 , 10 ]. MIBC has a propensity to become metastatic, and, once metastatic, it is associated with a 5-year survival of only 15% [ 1 , 10 ].…”

“…By contrast, approximately 25% of bladder cancers invade the muscle layers, and 5% have metastatic disease [ 1 , 2 , 4 , 5 , 8 , 10 ]. MIBC has a propensity to become metastatic, and, once metastatic, it is associated with a 5-year survival of only 15% [ 1 , 10 ]. Current international guidelines recommend platinum-based neoadjuvant chemotherapy (NAC), followed by radical cystectomy (RC) or bladder preservation strategies, with chemoradiation (trimodality therapy) in select patients; adjuvant chemotherapy is also an option for select patients) [ 1 , 2 , 4 , 5 , 6 , 7 , 8 , 10 ].…”

“…MIBC has a propensity to become metastatic, and, once metastatic, it is associated with a 5-year survival of only 15% [ 1 , 10 ]. Current international guidelines recommend platinum-based neoadjuvant chemotherapy (NAC), followed by radical cystectomy (RC) or bladder preservation strategies, with chemoradiation (trimodality therapy) in select patients; adjuvant chemotherapy is also an option for select patients) [ 1 , 2 , 4 , 5 , 6 , 7 , 8 , 10 ]. The most widely used platinum-based NACs include dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) regimens, and gemcitabine and cisplatin (GC) regimens [ 1 , 2 , 4 , 5 , 6 , 7 , 8 , 10 ].…”

“…Current international guidelines recommend platinum-based neoadjuvant chemotherapy (NAC), followed by radical cystectomy (RC) or bladder preservation strategies, with chemoradiation (trimodality therapy) in select patients; adjuvant chemotherapy is also an option for select patients) [ 1 , 2 , 4 , 5 , 6 , 7 , 8 , 10 ]. The most widely used platinum-based NACs include dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) regimens, and gemcitabine and cisplatin (GC) regimens [ 1 , 2 , 4 , 5 , 6 , 7 , 8 , 10 ]. Although only 5% of patients are metastatic at presentation, nearly 50% of patients with MIBC, undergoing curative-intent treatment, will eventually relapse and develop metastatic disease [ 2 , 4 , 5 , 6 , 7 , 8 ].…”