Emmprin Expression Predicts Response and Survival following Cisplatin Containing Chemotherapy for Bladder Cancer: A Validation Study

Tammer Hemdan, Per-Uno Malmström, Staffan Jahnson, Ulrika Segersten

Neoadjuvant chemotherapy before cystectomy is recommended. The subset of patients likely to benefit has not been identified. Our aim was to validate emmprin and survivin as markers of chemotherapy response. 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 expression was determined with immunohistochemistry. Expression was categorized according to predefined cutoffs reported in the literature. The data were analyzed with the Kaplan-Meier method and Cox models. Patients in the chemotherapy cohort with negative emmprin expression had a significantly higher downstaging overall survival (OS) compared to those with positive expression, 71 % versus 38 %, p<0.001. The corresponding figures for cancer-specific survival (CSS) were 76 % and 56 %, p< 0.027. In the cystectomy only cohort, emmprin expression was not associated with either OS (46 % and 35 %, p=0.23) or CSS (55 % and 51 %, p=0.64). The emmprin negative patients had an absolute risk reduction of 25% in overall survival (CI 11-40) and a number needed to treat (NNT) of 4 (CI 2.5-9.3). Survivin expression was not useful as biomarkers in this study. The limitations are the retrospective design and heterogeneity coupled with the time difference between the trials. Patients with emmprin negative tumors have a better response to neoadjuvant chemotherapy before cystectomy than those with positive expression.