Tammer Hemdan1, Per-Uno Malmström2, Staffan Jahnson2, Ulrika Segersten2. 1. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Urology, Faculty of Medical and Health Sciences, Linköping University (SJ), Linköping, Sweden. Electronic address: tammer.hemdan@surgsci.uu.se. 2. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Urology, Faculty of Medical and Health Sciences, Linköping University (SJ), Linköping, Sweden.
Abstract
PURPOSE:Neoadjuvant chemotherapy before cystectomy is recommended. To our knowledge the subset of patients likely to benefit has not been identified. We validate emmprin and survivin as markers of chemotherapy response. MATERIALS AND METHODS: Tumor specimens were obtained before therapy from a total of 250 patients with T1-T4 bladder cancer enrolled in 2 randomized trials comparing neoadjuvant chemotherapy before cystectomy with a surgery only arm. Protein expression was determined by immunohistochemistry. RESULTS: Expression was categorized according to predefined cutoffs reported in the literature. Data were analyzed with the Kaplan-Meier method and Cox models. Patients in the chemotherapy cohort with negative emmprin expression had significantly higher down staging overall survival than those with positive expression (71% vs 38%, p<0.001). The values for cancer specific survival were 76% and 56%, respectively (p<0.027). In the cystectomy only cohort emmprin expression was not associated with overall survival (46% vs 35%, p=0.23) or cancer specific survival (55% vs 51%, p=0.64). Emmprin negative patients had an absolute risk reduction of 25% in overall survival (95% CI 11-40) and a number needed to treat of 4 (95% CI 2.5-9.3). Survivin expression was not useful as a biomarker in this study. Limitations were the retrospective design and heterogeneity coupled with the time difference between the trials. CONCLUSIONS:Patients with emmprin negative tumors have a better response to neoadjuvant chemotherapy before cystectomy than those with positive expression.
RCT Entities:
PURPOSE: Neoadjuvant chemotherapy before cystectomy is recommended. To our knowledge the subset of patients likely to benefit has not been identified. We validate emmprin and survivin as markers of chemotherapy response. MATERIALS AND METHODS: Tumor specimens were obtained before therapy from a total of 250 patients with T1-T4 bladder cancer enrolled in 2 randomized trials comparing neoadjuvant chemotherapy before cystectomy with a surgery only arm. Protein expression was determined by immunohistochemistry. RESULTS: Expression was categorized according to predefined cutoffs reported in the literature. Data were analyzed with the Kaplan-Meier method and Cox models. Patients in the chemotherapy cohort with negative emmprin expression had significantly higher down staging overall survival than those with positive expression (71% vs 38%, p<0.001). The values for cancer specific survival were 76% and 56%, respectively (p<0.027). In the cystectomy only cohort emmprin expression was not associated with overall survival (46% vs 35%, p=0.23) or cancer specific survival (55% vs 51%, p=0.64). Emmprin negative patients had an absolute risk reduction of 25% in overall survival (95% CI 11-40) and a number needed to treat of 4 (95% CI 2.5-9.3). Survivin expression was not useful as a biomarker in this study. Limitations were the retrospective design and heterogeneity coupled with the time difference between the trials. CONCLUSIONS:Patients with emmprin negative tumors have a better response to neoadjuvant chemotherapy before cystectomy than those with positive expression.
Authors: Meera R Chappidi; Max Kates; Aaron Brant; Alexander S Baras; George J Netto; Phillip M Pierorazio; Noah M Hahn; Trinity J Bivalacqua Journal: Urology Date: 2017-01-16 Impact factor: 2.649
Authors: Minna Tervahartiala; Pekka Taimen; Tuomas Mirtti; Ilmari Koskinen; Thorsten Ecke; Sirpa Jalkanen; Peter J Boström Journal: Sci Rep Date: 2017-10-04 Impact factor: 4.379