Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer

Eur Urol. 2015 Feb;67(2):241-9. doi: 10.1016/j.eururo.2014.09.007. Epub 2014 Sep 23.

Abstract

Background: The efficacy of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (BCa) was established primarily with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), with complete response rates (pT0) as high as 38%. However, because of the comparable efficacy with better tolerability of gemcitabine and cisplatin (GC) in patients with metastatic disease, GC has become the most commonly used regimen in the neoadjuvant setting.

Objective: We aimed to assess real-world pathologic response rates to NAC with different regimens in a large, multicenter cohort.

Design, setting, and participants: Data were collected retrospectively at 19 centers on patients with clinical cT2-4aN0M0 urothelial carcinoma of the bladder who received at least three cycles of NAC, followed by radical cystectomy (RC), between 2000 and 2013.

Intervention: NAC and RC.

Outcome measurements and statistical analysis: The primary outcome was pathologic stage at cystectomy. Univariable and multivariable analyses were used to determine factors predictive of pT0N0 and ≤pT1N0 stages.

Results and limitations: Data were collected on 935 patients who met inclusion criteria. GC was used in the majority of the patients (n=602; 64.4%), followed by MVAC (n=183; 19.6%) and other regimens (n=144; 15.4%). The rates of pT0N0 and ≤pT1N0 pathologic response were 22.7% and 40.8%, respectively. The rate of pT0N0 disease for patients receiving GC was 23.9%, compared with 24.5% for MVAC (p=0.2). There was no difference between MVAC and GC in pT0N0 on multivariable analysis (odds ratio: 0.89 [95% confidence interval, 0.61-1.34]; p=0.6).

Conclusions: Response rates to NAC were lower than those reported in prospective randomized trials, and we did not discern a difference between MVAC and GC. Without any evidence from randomized prospective trials, the best NAC regimen for invasive BCa remains to be determined.

Patient summary: There was no apparent difference in the response rates to the two most common presurgical chemotherapy regimens for patients with bladder cancer.

Keywords: Complete pathologic response; Cystectomy; GC; MVAC; Neoadjuvant chemotherapy; Partial pathologic response; Urothelial cancer.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemotherapy, Adjuvant
  • Cisplatin / therapeutic use
  • Cystectomy
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Doxorubicin / therapeutic use
  • Europe
  • Female
  • Humans
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Multivariate Analysis
  • Neoadjuvant Therapy* / adverse effects
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • North America
  • Odds Ratio
  • Proportional Hazards Models
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / surgery
  • Vinblastine / therapeutic use

Substances

  • Deoxycytidine
  • Vinblastine
  • Doxorubicin
  • gemcitabine
  • Cisplatin
  • Methotrexate