title: Second-Line Chemotherapy for Metastatic Urothelial Carcinoma: Importance of Lymph Node-Only Metastasis as a Prognostic Factor and Construction of a Prognostic Model.
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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medical Oncology Department, King Hussein Cancer Center, Al-Jubeiha, Amman, Jordan. Electronic address: ssalah-salah@hotmail.com.
authors.forename: Samer
authors.initials: S
authors.lastname: Salah
authors.affiliation: Department of Oncology and Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Jae-Lyun
authors.initials: JL
authors.lastname: Lee
authors.affiliation: Medical Oncology Unit, Istituto Neurotraumatologico Italiano, Grottaferrata, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rozzi
authors.affiliation: Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitamura
authors.affiliation: Department of Urology, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Medical Oncology, Stanford University Medical Center, Stanford, CA.
authors.forename: Sandy
authors.initials: S
authors.lastname: Srinivas
authors.affiliation: Genitourinary, CNS and Sarcoma Tumor Unit, Vall d'Hebron University Hospital, Vall d´ Hebron Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Morales-Barrera
authors.affiliation: Genitourinary, CNS and Sarcoma Tumor Unit, Vall d'Hebron University Hospital, Vall d´ Hebron Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Carles
authors.affiliation: Medical Oncology Department, King Hussein Cancer Center, Al-Jubeiha, Amman, Jordan.
authors.forename: Rami
authors.initials: R
authors.lastname: Al-Wardat
authors.affiliation: Medical Oncology Department, King Hussein Cancer Center, Al-Jubeiha, Amman, Jordan.
authors.forename: Kamal
authors.initials: K
authors.lastname: Al-Rabi
authors.affiliation: Medical Oncology Department, King Hussein Cancer Center, Al-Jubeiha, Amman, Jordan.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Maakoseh
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: C111217:vinflunine; D014747:Vinblastine; D016190:Carboplatin; D002945:Cisplatin
keywords: Cancer progression; Chemotherapy; Prognosis; Survival; Urothelial carcinoma