Pd09-04 Characterization of Significant Genetic Drivers in Metastatic Prostate Cancer Tropism

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology II (PD09)1 May 2024PD09-04 CHARACTERIZATION OF SIGNIFICANT GENETIC DRIVERS IN METASTATIC PROSTATE CANCER TROPISM Mohammed Al-Toubat, Samuel Serrano, Allison H. Feibus, Seyedbehzad Jazayeri, and KC Balaji Mohammed Al-ToubatMohammed Al-Toubat , Samuel SerranoSamuel Serrano , Allison H. FeibusAllison H. Feibus , Seyedbehzad JazayeriSeyedbehzad Jazayeri , and KC BalajiKC Balaji View All Author Informationhttps://doi.org/10.1097/01.JU.0001008572.33286.63.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer (PC) primarily spreads to lymph nodes and bone, with much less occurrences of visceral metastasis. Notably, patients with lymph node only metastasis (LNM) exhibit significantly improved progression and overall survival compared to those with bone metastasis (BM). However, the genetic basis dictating the site of metastasis is yet to be clearly defined. In this study, we explored the genetic mutations specifically linked to LNM and BM tropism. METHODS: In our dataset comprising a total of 10,580 patients diagnosed with PCa, we carefully selected a study cohort of 1,011 patients presenting either LNM or BM. Excluding patients with missing data and those with concurrent LNM and BM, we aimed for a focused analysis of distinct mutations associated with lymph or bone tropism. The data was sourced from the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE) registry. We categorized the cohort into LNM or BM groups. Utilizing SPSS V28, we analyzed the difference in genetic mutation frequencies between the two groups and assessed the prognostic significance of these mutations. We considered a frequency rate of >5% and p-values <0.05 as statistically significant to maintain a true positive detection rate exceeding 95%. RESULTS: Our study included a total of 1,011 PC patients, with 622 patients (61.5%) having LNM and 389 patients (38.5%) having BM. LNM cases displayed higher incidences of TMPRSS2 (38.75% vs. 24.42%, p<0.001), ERG (31.99% vs. 17.48%, p<0.001), PTEN (30.23% vs. 23.14%, p<0.001), ZFHX3 (11.53% vs. 5.83%, p<0.001), CDK12 (9.00% vs. 4.88%, p<0.001), and KMT2C (9.65% vs. 6.43%, p<0.001) (Table 1). Interestingly, BM cases exhibited a higher mutation frequency of FOXA1 (17.22% vs. 10.77%, p<0.001). On survival analysis, the following genetic mutations were associated with lower overall survival compared to the median of 63 months (95% CI 45-73, p<0.001): TMPRSS2 38 months (95% CI 27-51, p<0.001), ERG 31 months (95% CI 22-49, p<0.001) and PTEN 31 months (95% CI 23-51, p<0.001) (Table 1). CONCLUSIONS: Our study identified FOXA1 mutation as distinctly associated with BM in PC. Despite the better prognosis associated with LNM, it displayed more frequent yet distinct mutations. These findings could be used to further our understanding on the tropism in PC metastasis. Source of Funding: N/A © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e180 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Mohammed Al-Toubat More articles by this author Samuel Serrano More articles by this author Allison H. Feibus More articles by this author Seyedbehzad Jazayeri More articles by this author KC Balaji More articles by this author Expand All Advertisement PDF downloadLoading ...