Pd57-11 Molecular Pathway Alterations Following Neoadjuvant Prostate Radiotherapy in a Prospective Trial

You have accessJournal of UrologyProstate Cancer: Localized: Radiation Therapy (PD57)1 May 2024PD57-11 MOLECULAR PATHWAY ALTERATIONS FOLLOWING NEOADJUVANT PROSTATE RADIOTHERAPY IN A PROSPECTIVE TRIAL Adam B. Weiner, Elai Davicioni, Robert E. Reiter, and Nicholas Nickols Adam B. WeinerAdam B. Weiner , Elai DavicioniElai Davicioni , Robert E. ReiterRobert E. Reiter , and Nicholas NickolsNicholas Nickols View All Author Informationhttps://doi.org/10.1097/01.JU.0001008808.16085.aa.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: For patients with high-risk prostate cancer (PCa), multimodal treatments can improve the chance for durable cure. Understanding how one treatment might alter cancer biology could help identify optimal treatment combinations. METHODS: We performed whole transcriptome RNA profiling of high-risk prostate tumors from patients enrolled in a prospective trial assessing stereotactic body radiation therapy neoadjuvant to radical prostatectomy (NCT02830165; n=6). Radiotherapy directed to the prostate and seminal vesicles was delivered in three fractions of 8 Gy in the course of 5 days a total of 2 weeks prior to surgery. Tissue microarrays from formalin-fixed paraffin-embedded tumors were submitted for RNA quantification and all comparisons were made using two-sided paired T-tests and false-discovery rate adjustments. RESULTS: Differential gene expression analyses identified 734 genes upregulated from pre- to post-SBRT (Figure 1). Gene set enrichment analyses identified pathway overlaps for these genes. Notably upregulated pathways included TNF-alpha, EMT, P53, and immune-based pathways. Upon evaluation of immunophenoscores, the only upregulated signature was Beta-2 microglobulin, a component of the antigen presenting MHC class I (p=0.0205). Immune cell deconvolution showed increased in M2 macrophages only, though this was not statistically significant (p=0.0505). In a panel of predicted drug response scores, post-SBRT tumors were more susceptible to taxane chemotherapy (p=0.0305). Notably, there were no significant alterations in genes associated with other targeted PCa therapies including androgen receptor pathways, B7-H3, or PSMA. CONCLUSIONS: Optimizing multimodal therapy by understanding how one treatment might render a tumor more susceptible to another treatment will be crucial. These data suggest SBRT affects gene expression patterns in the prostate in a manner that might alter susceptibilities to immune-based treatments and taxane chemotherapy. Download PPT Source of Funding: Simon-Strauss Foundation, UCLA Dr. Allen and Charlotte Ginsburg Fellowship in Precision Genomic Medicine, and the Prostate Cancer Foundation Young Investigator Award (ABW) © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1213 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Adam B. Weiner More articles by this author Elai Davicioni More articles by this author Robert E. Reiter More articles by this author Nicholas Nickols More articles by this author Expand All Advertisement PDF downloadLoading ...