Comparison of clinical outcomes in patients with localized or locally advanced urothelial carcinoma treated with neoadjuvant chemotherapy involving gemcitabine-cisplatin and high dose-intensity MVAC.

Yongjune Lee,Yong Mee Cho,Bumsik Hong,Young Seok Kim,Jae-Lyun Lee

doi:10.1007/s00432-021-03582-x

Abstract

To compare the efficacy and safety of high dose-intensity combination of methotrexate, vinblastine, adriamycin and cisplatin (HD MVAC) with gemcitabine plus cisplatin (GC) as a neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) or locally advanced upper tract urothelial cancer (UTUC). A retrospective analysis was conducted for patients with UC (cT2-4aN0-1M0) who received NAC from January 2011 and December 2017 at Asan Medical Center. Pathologic complete response (pCR), down-staging (< ypT2 and no N upstaging), disease-free survival (DFS), OS and safety were compared for each regimen. Out of a total of 277 patients, 176 patients received GC and 41 patients received HD MVAC. With the exception of age (patients receiving HD MVAC were younger; p = 0.002), other baseline characteristics were well balanced between groups. pCR rates were 27.0% for GC and 22.6% for HD MVAC (p = 0.62), and down-staging rate was 50.8% for GC and 58.1% for HD MVAC (p = 0.47). There were no differences in OS (72.1% vs 73.1% for GC vs HD MVAC; p = 0.58) and DFS (54.9% vs 63.3% for GC vs HD MVAC; p = 0.21) at 3years. HD MVAC with prophylactic G-CSF was associated with a higher incidence of febrile neutropenia (p < 0.001) than GC. The NAC regimen was not an independent prognostic factor for OS. Oncologic outcomes were not significantly different between the GC and HD MVAC when used as NAC in MIBC/UTUC.

Highlights

It is estimated that 550,000 new cases of bladder cancer occurred worldwide in 2018, with approximately onethird of patients presenting with the muscle-invasive form of the disease (MIBC)
We reviewed the rate of the patient's pathologic down-staging and pathologic complete response
The characteristics did not differ significantly between the two groups, with the exception of age: patients treated with high-dose intensity (HD) MVAC were younger than those treated with gemcitabine plus cisplatin (GC) (p=0.002)

Summary

Introduction

It is estimated that 550,000 new cases of bladder cancer occurred worldwide in 2018, with approximately onethird of patients presenting with the muscle-invasive form of the disease (MIBC). More than 20% of patients with non-muscle invasive bladder cancer progress to MIBC, resulting in 200,000 deaths annually(Bray et al 2018). The subsequent meta-analysis of 11 trials encompassing 3,005 patients supported the result that NAC led to an absolute improvement of 5-year overall survival (OS) by 5% and disease-free survival (DFS) by 9%(Advanced Bladder Cancer Meta-analysis Collaboration 2003). The GC (gemcitabine and cisplatin) regimen is preferred to MVAC based on comparative efficacy with a better safety profile and tolerability (von der Maase et al 2000). High-dose intensity (HD) MVAC with granulocyte colony-stimulating factor (G-CSF) support had statistically significant survival benefit and higher response rate, especially complete response, than MVAC, with comparable tolerance and fewer dose delays in metastatic urothelial cancer (Sternberg et al 2006; Sternberg et al 2001)

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