MP34-01 MOLECULAR SUBTYPES OF MUSCLE INVASIVE BLADDER CANCER ARE RELATED TO BENEFIT FROM NEOADJUVANT CHEMOTHERAPY: DEVELOPMENT OF A SINGLE SAMPLE PATIENT ASSAY (2017)

You have accessJournal of UrologyBladder Cancer: Invasive II1 Apr 2017MP34-01 MOLECULAR SUBTYPES OF MUSCLE INVASIVE BLADDER CANCER ARE RELATED TO BENEFIT FROM NEOADJUVANT CHEMOTHERAPY: DEVELOPMENT OF A SINGLE SAMPLE PATIENT ASSAY Roland Seiler, Hussam Al Deen Ashab, Nicholas Erho, Bas W.G. van Rhijn, Brian Winters, James Douglas, Kim Van Kessel, Elisabeth E. Fransen van de Putte, Matthew Sommerlad, Qiqi Wang, Voleak Choeurng, Ewan A. Gibb, Beatrix Palmer-Aronsten, Lucia L. Lam, Christine Buerki, Elai Davicioni, Gottfrid Sjödahl, Jordan Kardos, Katherine A. Hoadley, Seth P. Lerner, David J. McConkey, Woonyoung Choi, William Y. Kim, Bernhard Kiss, George N. Thalmann, Tilman Todenhöfer, Simon J. Crabb, Scott North, Ellen C. Zwarthoff, Joost L. Boormans, Jonathan Wright, Marc Dall'Era, Michiel S. van der Heijden, and Peter C. Black Roland SeilerRoland Seiler More articles by this author , Hussam Al Deen AshabHussam Al Deen Ashab More articles by this author , Nicholas ErhoNicholas Erho More articles by this author , Bas W.G. van RhijnBas W.G. van Rhijn More articles by this author , Brian WintersBrian Winters More articles by this author , James DouglasJames Douglas More articles by this author , Kim Van KesselKim Van Kessel More articles by this author , Elisabeth E. Fransen van de PutteElisabeth E. Fransen van de Putte More articles by this author , Matthew SommerladMatthew Sommerlad More articles by this author , Qiqi WangQiqi Wang More articles by this author , Voleak ChoeurngVoleak Choeurng More articles by this author , Ewan A. GibbEwan A. Gibb More articles by this author , Beatrix Palmer-AronstenBeatrix Palmer-Aronsten More articles by this author , Lucia L. LamLucia L. Lam More articles by this author , Christine BuerkiChristine Buerki More articles by this author , Elai DavicioniElai Davicioni More articles by this author , Gottfrid SjödahlGottfrid Sjödahl More articles by this author , Jordan KardosJordan Kardos More articles by this author , Katherine A. HoadleyKatherine A. Hoadley More articles by this author , Seth P. LernerSeth P. Lerner More articles by this author , David J. McConkeyDavid J. McConkey More articles by this author , Woonyoung ChoiWoonyoung Choi More articles by this author , William Y. KimWilliam Y. Kim More articles by this author , Bernhard KissBernhard Kiss More articles by this author , George N. ThalmannGeorge N. Thalmann More articles by this author , Tilman TodenhöferTilman Todenhöfer More articles by this author , Simon J. CrabbSimon J. Crabb More articles by this author , Scott NorthScott North More articles by this author , Ellen C. ZwarthoffEllen C. Zwarthoff More articles by this author , Joost L. BoormansJoost L. Boormans More articles by this author , Jonathan WrightJonathan Wright More articles by this author , Marc Dall'EraMarc Dall'Era More articles by this author , Michiel S. van der HeijdenMichiel S. van der Heijden 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.2017.02.1018AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Different methods for molecular subtyping of muscle-invasive bladder cancer (MIBC) have been described. Our goal was to investigate the impact of molecular subtypes in the context of neoadjuvant cisplatin-based chemotherapy (NAC) and to develop a single sample model for clinical use. METHODS Pre-NAC transurethral resection (TUR) specimens of 305 patients were profiled with the HumanExon microarray from Affymetrix. The original models (UNC, MDA, TCGA, Lund) for molecular subtyping were used to generate the subtype calls for these samples. Based on the biological and clinical significance, we developed a single sample genomic subtyping classifier (GSC) to predict modified consensus subtypes (claudin-low, basal, luminal-infiltrated and luminal). Overall survival (OS) according to subtype was analyzed and compared to OS in 376 non-NAC cases from three publicly available datasets. RESULTS The subtype calls in our NAC dataset were similar to previously published ratios and biological functions confirmed the concordance between the different subtyping methods (e.g. UNC luminal, MDA luminal, TCGA cluster I). Our GSC predicted the four consensus molecular subtypes with high accuracy (AUC >0.85). Extravesical extension of residual primary tumor (pT3/4) after NAC was observed more frequently in claudin-low and luminal-infiltrated subtypes. GSC was not significantly associated with major pathologic response (i.e., ypT<2N0). Patients with luminal tumors had the best outcome in both datasets with 3-year OS rates of 77% and 75%, respectively. The prognosis of patients with luminal-infiltrated tumors was inferior to that of luminal tumors and did not improve with NAC. Patients with claudin-low tumors had poor OS irrespective of treatment regimen. Patients with GSC basal tumors had a 3-year OS rate of 49.2% (p<0.001) in the non-NAC cohort compared to 77.8% (p<0.001) in the NAC cohort. CONCLUSIONS The benefit of NAC varies between molecular subtypes. The poor OS of claudin-low tumors even after NAC implies that these tumors are resistant to cisplatin-based chemotherapy, and these patients should be included in protocols investigating alternative treatment options like immunotherapy. The prognosis of patients with basal tumors improved the most when treated with NAC compared to surgery alone. Our findings require validation prior to clinical implementation. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e426 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Roland Seiler More articles by this author Hussam Al Deen Ashab More articles by this author Nicholas Erho More articles by this author Bas W.G. van Rhijn More articles by this author Brian Winters More articles by this author James Douglas More articles by this author Kim Van Kessel More articles by this author Elisabeth E. Fransen van de Putte More articles by this author Matthew Sommerlad More articles by this author Qiqi Wang More articles by this author Voleak Choeurng More articles by this author Ewan A. Gibb More articles by this author Beatrix Palmer-Aronsten More articles by this author Lucia L. Lam More articles by this author Christine Buerki More articles by this author Elai Davicioni More articles by this author Gottfrid Sjödahl More articles by this author Jordan Kardos More articles by this author Katherine A. Hoadley More articles by this author Seth P. Lerner More articles by this author David J. McConkey More articles by this author Woonyoung Choi More articles by this author William Y. Kim More articles by this author Bernhard Kiss More articles by this author George N. Thalmann More articles by this author Tilman Todenhöfer More articles by this author Simon J. Crabb More articles by this author Scott North More articles by this author Ellen C. Zwarthoff More articles by this author Joost L. Boormans More articles by this author Jonathan Wright More articles by this author Marc Dall'Era More articles by this author Michiel S. van der Heijden More articles by this author Peter C. 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