Decreased Overall and Bladder Cancer-Specific Mortality with Adjuvant Chemotherapy After Radical Cystectomy: Multivariable Competing Risk Analysis

Eur Urol. 2016 Jun;69(6):984-7. doi: 10.1016/j.eururo.2015.06.053. Epub 2015 Jul 17.

Abstract

Adding chemotherapy to radical cystectomy (RC) may improve outcome. Neoadjuvant treatment is advocated by guidelines based on meta-analysis data but is severely underused in clinical practice. Adjuvant treatment of patients at risk could be an alternative. We analyzed a sample of 798 patients who underwent RC between 1993 and 2011 for high-risk superficial or muscle-invasive urothelial or undifferentiated bladder cancer, of which 23% received adjuvant cisplatin-based chemotherapy and %5 received neoadjuvant chemotherapy. The use of adjuvant chemotherapy was an independent predictor of decreased overall mortality (hazard ratio [HR]: 0.50; 95% confidence interval [CI], 0.38-0.66; p<0.0001) and bladder cancer-specific mortality (HR: 0.71; 95% CI, 0.52-0.97; p=0.0321), but it was not associated with competing mortality. Similar figures were obtained when analyzing the number of cisplatin-containing cycles administered or when restricting the analysis to patients with lymph node-positive or extravesical but lymph node-negative disease, suggesting a mortality-reducing treatment effect after adjusting for several patient- and tumor-related confounders. Future trials should directly compare the concepts of neoadjuvant and adjuvant application of chemotherapy in candidates for RC.

Patient summary: Adjuvant chemotherapy may decrease overall and bladder cancer-specific mortality after radical cystectomy (RC). Future trials should directly compare the concepts of neoadjuvant and adjuvant application of chemotherapy in candidates for RC.

Keywords: Adjuvant; Bladder; Chemotherapy; Cisplatin; Comorbidity; Competing risk analysis; Cystectomy; Mortality; Proportional hazards model; Urologic neoplasms.

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemotherapy, Adjuvant
  • Cisplatin / administration & dosage
  • Cystectomy
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Epirubicin / administration & dosage
  • Follow-Up Studies
  • Gemcitabine
  • Humans
  • Lymphatic Metastasis
  • Methotrexate / administration & dosage
  • Neoadjuvant Therapy
  • Risk Assessment / methods
  • Survival Rate
  • Urinary Bladder Neoplasms / mortality*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / therapy*
  • Vinblastine / administration & dosage

Substances

  • Deoxycytidine
  • Epirubicin
  • Vinblastine
  • Cisplatin
  • Methotrexate
  • Gemcitabine