Pathological T0 Following Cisplatin-Based Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: A Network Meta-analysis

Clin Cancer Res. 2016 Mar 1;22(5):1086-94. doi: 10.1158/1078-0432.CCR-15-1208. Epub 2015 Oct 26.

Abstract

Purpose: To systematically assess and compare the relationship between various neoadjuvant chemotherapy regimens and pCR in patients with muscle-invasive bladder cancer.

Experimental design: We performed a literature search of PubMed, Embase, and the Cochrane Library for all articles published before March 2015 and according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. There were 17 articles that met the study eligibility criteria and were selected for the final analysis. A direct pair-wise meta-analysis was performed for studies that compared the same regimen. Finally, a Bayesian network meta-analysis was used to indirectly compare the regimens.

Results: In a pair-wise meta-analysis, the methotrexate/vinblastine/Adriamycin/cisplatin [MVAC; OR, 4.36; 95% confidence interval (CI), 2.71-7.02] and gemcitabine/cisplatin (GC) regimens (OR, 4.92; 95% CI, 2.93-8.24) were significantly associated with a better pCR than RC alone. In a network meta-analysis, there was no significant difference in terms of pCR achievement between the GC and MVAC regimens (OR, 1.14; 95% CI; 0.85-1.70). However, in a subgroup network meta-analysis that only included prospective randomized trials, the MVAC regimen was significantly correlated with a higher rate of pCR (OR, 5.75; 95% CI, 1.96-24.18).

Conclusions: The results of this meta-analysis suggest that a GC regimen was associated with a pCR rate that was similar to that of a MVAC regimen based on retrospective data, but only the MVAC regimen was proven to achieve pCR in prospective randomized trials. Additional prospective randomized trials comparing both regimens will be necessary to establish the optimal neoadjuvant chemotherapy regimen.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bayes Theorem
  • Carcinoma, Transitional Cell / drug therapy*
  • Carcinoma, Transitional Cell / pathology
  • Carcinoma, Transitional Cell / surgery
  • Cisplatin / therapeutic use
  • Cystectomy
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Doxorubicin / therapeutic use
  • Gemcitabine
  • Humans
  • Methotrexate / therapeutic use
  • Neoadjuvant Therapy*
  • Neoplasm Invasiveness / pathology
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / surgery
  • Vinblastine / therapeutic use

Substances

  • Deoxycytidine
  • Vinblastine
  • Doxorubicin
  • Cisplatin
  • Methotrexate
  • Gemcitabine

Supplementary concepts

  • M-VAC protocol
  • MEC protocol 1