PD33-11 NEOADJUVANT CHEMOTHERAPY IN BLADDER CANCER: P53-NESS IS ASSOCIATED WITH CHEMO-RESISTANCE AND UNFAVORABLE OUTCOME

Abstract

You have accessJournal of UrologyBladder Cancer: Invasive IV1 Apr 2016PD33-11 NEOADJUVANT CHEMOTHERAPY IN BLADDER CANCER: P53-NESS IS ASSOCIATED WITH CHEMO-RESISTANCE AND UNFAVORABLE OUTCOME Roland Seiler, Woonyoung Choi, Nicholas Erho, Bernhard Kiss, Lucia L Lam, Qici Wang, Christine Bürki, Elai Davicioni, George N Thalmann, David J McConkey, and Peter C Black Roland SeilerRoland Seiler More articles by this author , Woonyoung ChoiWoonyoung Choi More articles by this author , Nicholas ErhoNicholas Erho More articles by this author , Bernhard KissBernhard Kiss More articles by this author , Lucia L LamLucia L Lam More articles by this author , Qici WangQici Wang More articles by this author , Christine BürkiChristine Bürki More articles by this author , Elai DavicioniElai Davicioni More articles by this author , George N ThalmannGeorge N Thalmann More articles by this author , David J McConkeyDavid J McConkey More articles by this author , and Peter C BlackPeter C Black More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.720AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Muscle-invasive bladder cancer (MIBC) can molecularly be grouped into intrinsic basal and luminal subtypes. Tumors within the luminal subtype and a ′p53-like′ gene expression have been found to be resistant to neoadjuvant chemotherapy (NAC) with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). We investigated the response of these subtypes to gemcitabine plus cisplatin (GC), the other major frontline NAC regimen in this disease setting. METHODS Fifty-two MIBC patients received neoadjuvant GC followed by cystectomy. At cystectomy, 37 (71%) patients did not respond to NAC (ypT≥2 or any ypN1-3). With the RNeasy FFPE kit (Qiagen) RNA was isolated from pre-NAC transurethral resection (TUR) specimens and post-NAC cystectomy specimens. After cDNA ampliciation and labelling with the Ovation WTA FFPE system and Encore Biotin Module (NuGen) samples were hybridized to GeneChip Human Exon 1.0 ST oligonucleotide microarrays (Affymetrix). The tumors were assigned to the intrinsic subtypes using a one nearest neighbor prediction model. RESULTS Unsupervised hierarchical clustering separated the tumors into clusters characterized by non-overlapping expression of basal or luminal biomarkers. Assignment of pretreatment TUR tumors to subtypes yielded the expected ratios of basal, p53-like, and luminal tumors of which 5/14 (36%), 2/15 (17%) and 8/23 (35%) showed pathological down staging (<ypT2 any ypN neg), respectively. p53-like tumors had significantly the shortest recurrence free (p=0.006) and overall survival (p=0.003) compared to the other subtypes. Basal tumors with an enrichment of an immune signature responded to NAC, although this did not reach statistical significance. Matched analysis of tumors before and after NAC revealed an enrichment for p53-like tumors at cystectomy. CONCLUSIONS In line with the MVAC data, p53-like tumors displayed resistance to neoadjuvant GC. Moreover, p53-ness is associated with unfavorable outcome in MIBC treated with NAC. If these results are confirmed prospectively, patients with p53-like tumors should not be treated with cisplatin-based chemotherapy and should instead be steered to immediate cystectomy or clinical trials of novel therapies. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e770 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Roland Seiler More articles by this author Woonyoung Choi More articles by this author Nicholas Erho More articles by this author Bernhard Kiss More articles by this author Lucia L Lam More articles by this author Qici Wang More articles by this author Christine Bürki More articles by this author Elai Davicioni More articles by this author George N Thalmann More articles by this author David J McConkey More articles by this author Peter C Black More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...