title: Early results of the value of p53 in predicting survival in a homogeneous cohort of patients with invasive bladder cancer treated with a neoadjuvant carboplatin-based regimen (M-CAVI).
abstract: OBJECTIVE
  Several reports on prognostic factors for infiltrating-bladder cancer have given controversial results. We assessed the prognostic value of p53 nuclear overexpression together with known prognostic factors for survival in patients with invasive T2-4 N0 M0 bladder cancer treated with neoadjuvant chemotherapy.
  
  
  METHODS
  Thirty-five paraffinized tumor samples from initial transurethral resection of patients with bladder cancer were analyzed immunohistochemically to detect overexpression of p53 protein. Patients were treated with 3 to 4 cycles of neoadjuvant methotrexate, carboplatin, and vinblastine (M-CAVI) and then underwent radical cystectomy. Prechemotherapy, treatment, and postchemotherapy factors were analyzed for correlation with survival by univariate and multivariate analysis. Fifty-seven percent of tumors were positive for p53 protein, 71.5% had grade III-IV tumors, and 72% had organ-confined disease. The median follow-up was 20 months (range 5-71+).
  
  
  RESULTS
  By univariate analysis, the significant pretreatment factors were initial tumor (T) stage (P < 0.0001) and the male sex (P = 0.03). Five postchemotherapy variables were found significant: surgery performed according to protocol (P = 0.003), overall clinical (P = 0.004), and overall pathologic (P = 0.02) response to therapy, postchemotherapy pathologic stage (P = 0.0002), and tumor status after surgery (P = 0.0006). By multivariate analysis, the initial prechemotherapy T stage was the only factor that demonstrated independent significance.
  
  
  CONCLUSIONS
  Although the median follow-up of the study is still too short, in this group of patients treated with a neoadjuvant carboplatin-based regimen, a classical variable (prechemotherapy T stage) rather than p53 nuclear overexpression was an independent prognostic factor for survival. Further follow-up will be required to assess the value of p53 overexpression as a prognostic factor in invasive bladder cancer patients treated with neoadjuvant carboplatin-based chemotherapy.
authors.affiliation: Medical Oncology Section, Hospital General Universitari Vall d'Hebron, Barcelona, Spain. aribas@surgery.medsch.ucla.edu
authors.forename: A
authors.initials: A
authors.lastname: Ribas
authors.forename: J
authors.initials: J
authors.lastname: Bellmunt
authors.forename: J
authors.initials: J
authors.lastname: Albanell
authors.forename: I
authors.initials: I
authors.lastname: De Torres
authors.forename: B
authors.initials: B
authors.lastname: Bermejo
authors.forename: J A
authors.initials: JA
authors.lastname: De Torres
authors.forename: J
authors.initials: J
authors.lastname: Morote
authors.forename: E
authors.initials: E
authors.lastname: Gallardo
authors.forename: R
authors.initials: R
authors.lastname: Vera
authors.forename: J
authors.initials: J
authors.lastname: Carulla
authors.forename: L A
authors.initials: LA
authors.lastname: Sole-Calvo
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000097:blood*; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D016159:Tumor Suppressor Protein p53; D014747:Vinblastine; D016190:Carboplatin; D008727:Methotrexate