1787 DIHYDROPYRIMIDINE DEHYDROGENASE IS ASSOCIATED WITH CLINICAL OUTCOME IN T1G3 BLADDER CANCER PATIENTS TREATED WITH BACILLUS CALMETTE-GUERIN

Abstract

You have accessJournal of UrologyBladder Cancer: Superficial (II)1 Apr 20131787 DIHYDROPYRIMIDINE DEHYDROGENASE IS ASSOCIATED WITH CLINICAL OUTCOME IN T1G3 BLADDER CANCER PATIENTS TREATED WITH BACILLUS CALMETTE-GUERIN Hiroki Ide, Eiji Kikuchi, Shuji Mikami, Akira Miyajima, and Mototsugu Oya Hiroki IdeHiroki Ide Tokyo, Japan More articles by this author , Eiji KikuchiEiji Kikuchi Tokyo, Japan More articles by this author , Shuji MikamiShuji Mikami Tokyo, Japan More articles by this author , Akira MiyajimaAkira Miyajima Tokyo, Japan More articles by this author , and Mototsugu OyaMototsugu Oya Tokyo, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2877AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recently, it was reported that thymidylate synthase (TS), a target enzyme of 5-fluorouracil (5-FU), and dihydropyrimidine dehydrogenase (DPD), which degraded most of 5-FU, were significant prognostic factors for invasive bladder cancer. However, few studies that evaluated the roles of them in recurrence focused on non-muscle invasive bladder cancer, especially T1G3 tumors. In the present study, we used the Dannenberg tumor profile (DTP) method, which is a highly accurate method for the measurement of RNA that involves a special technique for its extraction from paraffin-embedded specimens, to evaluate the role of 5-FU related enzymes as predictive biomarkers in T1G3 tumors. METHODS The subjects were 45 patients with T1G3 tumors who were surgically treated at our institution. The median follow-up was 37 months (3 to 159 months). Twenty-eight patients received adjuvant BCG instillation. The mRNA levels of TS and DPD were analyzed using the DTP method. Recurrence-free survival (RFS) and progression-free survival (PFS) were evaluated by the Kaplan-Meier method. Cox proportional hazards regression analysis was used to assess the predictors for RFS and PFS. RESULTS Overall, the mean DPD and TS mRNA levels were 1.255±0.179 and 9.273±1.098, respectively. BCG instillation was significantly associated with RFS and an independent predictor for RFS (p<0.01). The TS and DPD mRNA levels were not significantly associated with RFS and PFS. Recurrence and progression were observed in 13 (46.4%) and 6 (21.4%) patients, respectively, among those treated with BCG. In patients treated with BCG, the mean DPD mRNA level with recurrence was 1,341±0.426, compared to 0.994±0.335 without it (p<0.05). On the other hand, no significant difference in TS level between patients with recurrence and without it was observed. In patients treated with BCG, DPD was significantly associated with PFS (p=0.047). Multivariate analysis revealed DPD (p=0.048, hazard ratio 4.759, 95%CI: 0.868-26.098) was an independent predictor for PFS. The 5-year PFS rate was 85.6% in patients with lower DPD compared to 63.5% in those with higher DPD. The mean DPD mRNA level with progression was 1.884±0.679, compared to 0.980±0.279 without it (p<0.05). Meanwhile, the TS mRNA level was not significantly associated with PFS. CONCLUSIONS DPD may be a key enzyme involved in recurrence and progression in T1G3 patients treated with BCG therapy. Combination therapy of BCG with a 5-FU-based agent having a strong DPD inhibitor such as S-1 might be a novel therapeutic strategy in T1G3 tumors. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e734 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hiroki Ide Tokyo, Japan More articles by this author Eiji Kikuchi Tokyo, Japan More articles by this author Shuji Mikami Tokyo, Japan More articles by this author Akira Miyajima Tokyo, Japan More articles by this author Mototsugu Oya Tokyo, Japan More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...