MP45-17 COMPARISON OF THE PROGNOSTIC AND PREDICTIVE VALUE OF THE BIOMARKERS ERCC1 AND KI67 IN PATIENTS ENROLLED IN TWO RANDOMIZED STUDIES OF NEOADJUVANT CHEMOTHERAPY WITH OR WITHOUT CYSTECTOMY

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research II1 Apr 2015MP45-17 COMPARISON OF THE PROGNOSTIC AND PREDICTIVE VALUE OF THE BIOMARKERS ERCC1 AND KI67 IN PATIENTS ENROLLED IN TWO RANDOMIZED STUDIES OF NEOADJUVANT CHEMOTHERAPY WITH OR WITHOUT CYSTECTOMY Tammer Hemdan, Ulrika Segersten, and Per-Uno Malmström Tammer HemdanTammer Hemdan More articles by this author , Ulrika SegerstenUlrika Segersten More articles by this author , and Per-Uno MalmströmPer-Uno Malmström More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1515AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Neoadjuvant chemotherapy before cystectomy is recommended in guidelines. The subset of patient likely to benefit has not been identified. Negative ERCC1 expression has been associated with sensitivity to cisplatin in lung cancer and in uncontrolled studies on bladder cancer. Our aim was to analyze ERCC1 and ki67 as predictive markers of chemotherapy response and prognostically for surgery only. METHODS Tumor specimens were obtained before therapy from 250 patients with T1-T4 bladder cancer enrolled in two randomized trials comparing neoadjuvant chemotherapy before cystectomy with a surgery only arm. Protein status was determined with immunohistochemistry. Lack of ERCC1 staining was called negative, while all levels of staining were called positive. Only extent was evaluated for ki67 and the cut-off used was 20%. Overall survival was analyzed with the Kaplan-Meier method and a Cox model. RESULTS Positive ERCC1 staining was found in 75% of the specimens. Overall survival was similar for the expression categories in the chemotherapy arm while a significant difference was found in the control arm (p=0.001). The negative patients had a risk reduction of 45% (CI 23-66) and number needed to treat (NNT) of 3 (CI 1.5-4.3). Corresponding result for positive tumors was a reduction of 13% (CI -1 to27%) and a NNT of 8. The ki67 expression was neither prognostic nor predictive of outcome. Currently ERCC1 status is further analyzed by a more specific antibody (4F9). CONCLUSIONS ERCC1-negative tumors respond to neoadjuvant cisplatin-based chemotherapy, whereas patients with ERCC1-positive tumors have only a minimal benefit. In cystectomy only patients negative expression was correlated to poor survival © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e542 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tammer Hemdan More articles by this author Ulrika Segersten More articles by this author Per-Uno Malmström More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...