Presentation Authors: Mauro Ragonese, Luca Di Gianfrancesco, Giovanni Schinzari, Giuseppe Palermo, Marco Racioppi, PierFrancesco Bassi*, Rome, Italy
Introduction: Multiple molecular biomarkers have been proposed as predictors of neoadjuvant chemotherapy efficacy in urothelial muscle-invasive bladder cancer. Despite emerging evidences, these data are not yet translated into clinical practice. Our study evaluates the prognostic and predictive role of the expression of the human equilibrative nucleoside transporter 1 (hENT1) and the excision repair cross complementing 1 (ERCC1) in bladder cancer receiving neoadjuvant chemotherapy with gemcitabine and platinum derivatives.
Methods: Clinical records of forty patients with muscle-invasive bladder cancer who received neoadjuvant gemcitabine-platinum combination chemotherapy were retrospectively analyzed. The primary endpoint was histopathologic complete response (pCR) rate and the secondary endpoints were disease-free survival (DFS) and overall survival (OS). Clinical and histopathologic parameters along with ERCC1 and hENT1 expression, assessed by RT-PCR in chemo-naive primary bladder tumor specimen, were examined and correlated with pCR rates, DFS and OS. To test the hypothesis that patients with hENT1+ve and low ERCC1 level tumors had better outcomes, an exploratory analysis of pCR rate was performed in two prognostic subgroups: subgroup A, containing hENT1+ve and low ERCC1 level population; subgroup B, containing hENT1-ve and high ERCC1 level population plus patients having both expressions of hENT1 and ERCC1 with same tendency.
Results: pCR rate in the whole population was 40% (16 out of 40 patients), while in hENT1+ve and low ERCC1 level population (subgroup A) was 61.5% (16 out of 26 patients) which was signicantly higher than in patients with either both expressions of biomarerks with same tendency or both the detrimental expressions (subgroup B), where 0% (0 out of 14 patients) achieved a pCR (Fisher's exact test P=0.01465). Analyzing independently each predictive biomarker, in patients with low ERCC1 level, the pathologic complete response rate was significantly higher than in patients with high ERCC1 level (Fisher's exact test P=0.0419), while regarding hENT1 expression, 16 out of 32 (50%) hENT1+ve patients achieved a pCR (Fisher's exact test P=0.1166). Even if Median DFS and median OS in patients within subgroup A and subgroup B were not reached due to the short median follow-up (14 months, range 4.5-46.7) and to the small number of events occurred, the Kaplan Meyer for DFS showed a significant difference between the two subgroups (p=0.035).
Conclusions: Our results showed that combined expression of ERCC1 and hENT1 may predict pCR in patients with bladder cancer who received neoadjuvant chemotherapy with Gemcitabine and platinum derivatives. Further studies with larger number of patients and longer follow-up are needed to confirm these results and to validate their impact on survival.