PD52-12 ANALYSIS OF THE PROGNOSTIC SIGNIFICANCE OF CIRCULATING TUMOR DNA (CTDNA) IN METASTATIC CASTRATE RESISTANT PROSTATE CANCER (MCRPC)

Abstract

You have accessJournal of UrologyProstate Cancer: Markers II (PD52)1 Apr 2020PD52-12 ANALYSIS OF THE PROGNOSTIC SIGNIFICANCE OF CIRCULATING TUMOR DNA (CTDNA) IN METASTATIC CASTRATE RESISTANT PROSTATE CANCER (MCRPC) Justin Shaya*, J. Michael Randall, Frederick Millard, Razelle Kurzrock, J. Kellogg Parsons, Pablo Tamayo, and Rana McKay Justin Shaya*Justin Shaya* More articles by this author , J. Michael RandallJ. Michael Randall More articles by this author , Frederick MillardFrederick Millard More articles by this author , Razelle KurzrockRazelle Kurzrock More articles by this author , J. Kellogg ParsonsJ. Kellogg Parsons More articles by this author , Pablo TamayoPablo Tamayo More articles by this author , and Rana McKayRana McKay More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000954.012AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Given the technical limitations of obtaining tissue next-generation sequencing, there has been considerable interest in blood ctDNA to assess genomic alterations in mCRPC. We examined the genomic landscape and prognostic significance of ctDNA in mCRPC. METHODS: Single center retrospective analysis of mCRPC patients who underwent ctDNA genomic profiling using Guardant360. Overall survival (OS) and time to progression (TTP) were examined and stratified by the presence of tumor suppressor mutations (p53, PTEN, Rb), androgen receptor (AR) amplification or mutation, number of genomic alterations, and highest allelic fraction of detected mutations. RESULTS: At the time of ctDNA collection, all patients (n=46) had mCRPC with bone metastases present in 100% of patients and visceral metastases present in 17.3%. Median age at ctDNA collection was 71 years, median time from CRPC diagnosis to ctDNA was 13 months (range 0-45), and median follow-up time from CRPC diagnosis was 17.5 months (4-40). The most common alterations present were TP53 mutation (41.3%), AR amplification (30.4%), and CDK6 amplification (21.7%). Actionable mutations were detected in BRCA1 (4.3%), BRCA2 (4.3%), ATM (2.2%), and PMS2 (2.2%). The median number of genomic alterations was 2 (0-8) and the median ctDNA allelic fraction was 4.6% (0-86.9%). Median OS of the cohort was 36 months. The presence of a tumor suppressor mutation, > 2 genomic alterations, and >5% mutation allelic frequency was associated with inferior OS (Table 1). In terms of time to progression on 1st line abiraterone or enzalutamide, the presence of an AR amplification or mutation was associated with significantly worse TTP of 6.9 months vs 13.5 months (p-0.015). Lastly, median PSA of the cohort was 73.5 and PSA was weakly associated with both ctDNA allelic fraction (r2-0.064, p-0.01) and number of genomic alterations (r2-0.088, p<0.001) by Pearson correlation. CONCLUSIONS: ctDNA is frequently detected in mCRPC; and the type, number and frequency of alterations are potentially prognostic of OS in mCRPC. Ongoing studies are needed to assess concordance of ctDNA with tissue NGS and the predictability of ctDNA. Source of Funding: None. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1094-e1095 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Justin Shaya* More articles by this author J. Michael Randall More articles by this author Frederick Millard More articles by this author Razelle Kurzrock More articles by this author J. Kellogg Parsons More articles by this author Pablo Tamayo More articles by this author Rana McKay More articles by this author Expand All Advertisement PDF downloadLoading ...