MP68-12 IMPACT OF SPOP MUTATION ON PROSTATE CANCER PROGNOSIS

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology II (MP68)1 Apr 2019MP68-12 IMPACT OF SPOP MUTATION ON PROSTATE CANCER PROGNOSIS Jonathan Shoag*, Deli Liu, Xiayoue Ma, Clara Oromendia, Cynthia Angulo, Seagle Liu, Yang Liu, Elai Davicioni, and Christopher Barbieri Jonathan Shoag*Jonathan Shoag* More articles by this author , Deli LiuDeli Liu More articles by this author , Xiayoue MaXiayoue Ma More articles by this author , Clara OromendiaClara Oromendia More articles by this author , Cynthia AnguloCynthia Angulo More articles by this author , Seagle LiuSeagle Liu More articles by this author , Yang LiuYang Liu More articles by this author , Elai DavicioniElai Davicioni More articles by this author , and Christopher BarbieriChristopher Barbieri More articles by this author View All Author Informationhttps://doi.org/10.1097/01.JU.0000557027.87083.d3AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: SPOP mutation defines one of the dominant prostate cancer subclasses, present in ∼10% of cases, or 16,000 newly diagnosed men in 2018. The independent impact of SPOP mutation on prostate cancer prognosis is unknown. Here, we define the impact of SPOP mutation on prostate cancer pathologic and clinical outcomes and determine whether delineation of this subclass impacts prostate cancer prognostic models. METHODS: Molecularly profiled samples obtained as part of a multi-institutional cohort, the Decipher retrospective cohort, Decipher prospective cohort, and The Cancer Genome Atlas were utilized. SPOP mutation was defined either by DNA sequencing, or according to a highly accurate subclass predictor based on transcriptional data developed by our group. We assessed the relationship between SPOP mutation and clinical outcomes, and evaluated the utility of adding SPOP mutational status to prognostic models using distinct training and validation cohorts. RESULTS: Incorporating results from multivariable proportional hazards models from all four cohorts using a fixed effects model demonstrated that SPOP mutation was associated with favorable pathology independent of preoperative prostate specific antigen (PSA), age, and pathologic Gleason score, OR 0.57, 95% confidence interval (CI) 0.34 to 0.93. SPOP mutation was not associated with biochemical recurrence, the development of metastases, or cancer specific mortality. The addition of SPOP status did not meaningfully alter prognostic models for adverse pathology, with a probability of difference in the area under the curve with and without addition of SPOP status of 0.93. Models incorporating SPOP status did not alter the positive and negative predictive ability of models for adverse pathology in a clinically meaningful fashion when tested in a validation cohort. CONCLUSIONS: The presence of SPOP mutation is an independent predictor of favorable pathology at prostatectomy. Delineation of this subtype was not clinically useful in prognostic models. This finding underscores some of the challenges associated with incorporating genomics into prostate cancer prognostic models, and highlights the need for understanding the impact of progression events as they relate to genomic subclass. Source of Funding: None New York, NY; Vancouver, Canada; New York, NY© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e979-e980 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jonathan Shoag* More articles by this author Deli Liu More articles by this author Xiayoue Ma More articles by this author Clara Oromendia More articles by this author Cynthia Angulo More articles by this author Seagle Liu More articles by this author Yang Liu More articles by this author Elai Davicioni More articles by this author Christopher Barbieri More articles by this author Expand All Advertisement PDF downloadLoading ...