Abstract
Simple SummaryCurrently, platinum-based neoadjuvant chemotherapy (NAC) is becoming a standard treatment for use in patients with muscle-invasive bladder cancer. However, comparisons of oncologic outcomes for the two most commonly used NAC regimens, ddMVAC (dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin) and GC (gemcitabine and cisplatin), are controversial. We sought to compare the oncologic outcomes of these two regimens via a systematic review and meta-analysis of all the available studies published to date. Through this, we aimed to provide evidence on the optimal NAC regimen for use in muscle-invasive bladder cancer.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.
Highlights
Bladder cancer manifests in most cases as a non-muscle invasive disease and requires only local treatment
All trials enrolled patients diagnosed with muscle-invasive bladder cancer (MIBC) who had undergone either gemcitabine and cisplatin (GC) or dose-dense MVAC (ddMVAC) as neoadjuvant chemotherapy (NAC)
Since the Southwest Oncology Group reported a positive effect of NAC using MVAC for MIBC in 2003 [10], NAC before radical cystectomy and pelvic lymph node dissection has been used as the standard treatment for MIBC
Summary
Bladder cancer manifests in most cases as a non-muscle invasive disease and requires only local treatment. Radical cystectomy with bilateral pelvic lymph node dissection is a standard local treatment for non-metastatic muscle-invasive bladder cancer (MIBC). A large proportion of MIBC patients experience relapse and eventually die after radical cystectomy and pelvic lymph node dissection [2]. Local recurrence rates range from 30% to 54%, and distant relapses occur in up to 50% of cases [3,4,5,6]. Perioperative chemotherapy, such as adjuvant or neoadjuvant therapy, is used for MIBC. In randomized clinical trials (RCTs) and meta-analyses evaluating the clinical outcomes of neoadjuvant chemotherapy (NAC) [7,8,9], an increase in overall survival (OS) by 5–6% for NAC, compared with radical cystectomy alone, was reported in MIBC patients [10,11]
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