MP39-01 CHARACTERIZING RECURRENT AND LETHAL SMALL RENAL MASSES IN CLEAR CELL RENAL CELL CARCINOMA USING SOMATIC MUTATIONS

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I1 Apr 2017MP39-01 CHARACTERIZING RECURRENT AND LETHAL SMALL RENAL MASSES IN CLEAR CELL RENAL CELL CARCINOMA USING SOMATIC MUTATIONS Brandon Manley, Ed Reznik, Maria Becerra, Jozefina Casuscelli, Daniel Tennenbaum, Mazyar Ghanaat, Mahyar Kashan, Almedina Redzematovic, Yusuke Sato, Maria Arcila, Martin Voss, Darren Feldman, Paul Russo, Jonathan Coleman, James Hsieh, and Ari Hakimi Brandon ManleyBrandon Manley More articles by this author , Ed ReznikEd Reznik More articles by this author , Maria BecerraMaria Becerra More articles by this author , Jozefina CasuscelliJozefina Casuscelli More articles by this author , Daniel TennenbaumDaniel Tennenbaum More articles by this author , Mazyar GhanaatMazyar Ghanaat More articles by this author , Mahyar KashanMahyar Kashan More articles by this author , Almedina RedzematovicAlmedina Redzematovic More articles by this author , Yusuke SatoYusuke Sato More articles by this author , Maria ArcilaMaria Arcila More articles by this author , Martin VossMartin Voss More articles by this author , Darren FeldmanDarren Feldman More articles by this author , Paul RussoPaul Russo More articles by this author , Jonathan ColemanJonathan Coleman More articles by this author , James HsiehJames Hsieh More articles by this author , and Ari HakimiAri Hakimi More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1175AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Management of small renal masses (SRMs) may include active surveillance (AS) in selected patients. Clear cell renal cell carcinoma (ccRCC) is the most common histology among these SRMs. Current AS algorithms largely rely on growth parameters of the masses measured over time. We sought to identify genomic biomarkers that could potentially refine the management of SRMs, especially in patients being evaluated for AS. METHODS From four databases, we identified 205 patients who had SRMs (<4 cm) at time of surgery and had sequencing performed on their primary tumors. We included patients from our institutional prospective database (n=25), and from three publicly available cohorts, The Cancer Genome Atlas (n=110), University of Tokyo (n=38), and The International Cancer Genome Consortium (n=32). We analyzed the frequency of recurrent somatic mutations among the entire cohort. Using Chi-Square analysis, the frequency of mutations that occurred in at least 5% of patients were compared in patients who had recurrence or died from their disease during follow-up with those who did not. Kaplan-Meier survival plots were generated for these frequently mutated genes. Analysis was adjusted for multiple testing using the false discovery rate. RESULTS Median follow-up was 43.1 months among survivors. Mutations in VHL, PBRM1, SETD2, BAP1, KDM5C, and MTOR were present in more than 5% of tumors. Of the 205 patients, 25 (12.2%) had recurrence or died of their disease. Mutations in KDM5C were found to be significantly more common in those who had recurrence or died of their disease (24% vs. 4%; adjusted p=0.02). Survival analysis showed patients with KDM5C having statistically significant inferior cancer-specific survival (adjusted p=<0.01) and a trend for inferior survival in those with SETD2 mutations (adjusted p=0.11) (Figure 1). CONCLUSIONS We identified mutations in SRMs that are associated with recurrence and lethality. The strongest association was seen with KDM5Cmutations. Use of these potential genomic biomarkers may improve risk stratification of patients with SRMs and for those who may be appropriate for AS. Prospective evaluation of these markers is needed. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e492-e493 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Brandon Manley More articles by this author Ed Reznik More articles by this author Maria Becerra More articles by this author Jozefina Casuscelli More articles by this author Daniel Tennenbaum More articles by this author Mazyar Ghanaat More articles by this author Mahyar Kashan More articles by this author Almedina Redzematovic More articles by this author Yusuke Sato More articles by this author Maria Arcila More articles by this author Martin Voss More articles by this author Darren Feldman More articles by this author Paul Russo More articles by this author Jonathan Coleman More articles by this author James Hsieh More articles by this author Ari Hakimi More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...