Second-Line Chemotherapy for Metastatic Urothelial Carcinoma: Importance of Lymph Node-Only Metastasis as a Prognostic Factor and Construction of a Prognostic Model

Clin Genitourin Cancer. 2016 Jun;14(3):255-60. doi: 10.1016/j.clgc.2015.10.006. Epub 2015 Oct 24.

Abstract

Background: A prognostic model for patients with metastatic urothelial carcinoma (UC) progressing after platinum-based therapy was constructed from data from the phase III vinflunine trial. However, prognostic information for patients treated with other regimens is limited.

Materials and methods: We pooled individual patient data from 7 second-line studies and analyzed the influence of factors of interest on overall survival (OS) through univariate and multivariate analysis. A prognostic model was constructed, and data from an independent series were used for validation.

Results: The data from 193 patients were pooled. The second-line chemotherapy regimen was single-agent taxane in 54 patients (28%), a platinum-based combination in 47 (24%), and a non-platinum combination in 92 (48%). On multivariate analysis, Eastern Cooperative Oncology Group performance status ≥ 1, hemoglobin < 10 g/dL, and metastatic patterns other than lymph node-only metastasis emerged as independent adverse prognostic factors. Patients with all 3 factors (poor risk), 1 to 2 factors (intermediate risk), and no factors (good risk) had a median OS of 3.1, 8.7, and 16.5 months, respectively (P < .0001). The corresponding median OS for the validation series (n = 44) was 3.3, 8.1, and 13.3 months (P = .023). Furthermore, platinum-based regimens were independently associated with an OS benefit compared with other regimens (hazard ratio, 0.31; 95% confidence interval, 0.18-0.53; P < .0001).

Conclusion: We have proposed and validated a prognostic model for patients with metastatic UC who were eligible for second-line therapy. The proposed model could prove helpful for risk stratification. Furthermore, our data suggest that testing second-line platinum-based regimens in randomized trials is warranted.

Keywords: Cancer progression; Chemotherapy; Prognosis; Survival; Urothelial carcinoma.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Carcinoma, Transitional Cell / drug therapy*
  • Carcinoma, Transitional Cell / mortality
  • Carcinoma, Transitional Cell / secondary
  • Cisplatin / administration & dosage
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Treatment Outcome
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology
  • Vinblastine / administration & dosage
  • Vinblastine / analogs & derivatives

Substances

  • vinflunine
  • Vinblastine
  • Carboplatin
  • Cisplatin