Mp10-05 Multigene Assays to Predict Malignancy and Drug Efficacy in Renal Cell Carcinoma and Pan-Cancer: Development and Dual External Validation

You have accessJournal of UrologyKidney Cancer: Advanced (including Drug Therapy) I (MP10)1 May 2024MP10-05 MULTIGENE ASSAYS TO PREDICT MALIGNANCY AND DRUG EFFICACY IN RENAL CELL CARCINOMA AND PAN-CANCER: DEVELOPMENT AND DUAL EXTERNAL VALIDATION Chenghao Tan, Shiming He, Xuesong Li, Sainan Zhu, Ninghan Feng, Qun He, Libo Liu, Zhisong He, Liqun Zhou, and Gengyan Xiong Chenghao TanChenghao Tan , Shiming HeShiming He , Xuesong LiXuesong Li , Sainan ZhuSainan Zhu , Ninghan FengNinghan Feng , Qun HeQun He , Libo LiuLibo Liu , Zhisong HeZhisong He , Liqun ZhouLiqun Zhou , and Gengyan XiongGengyan Xiong View All Author Informationhttps://doi.org/10.1097/01.JU.0001008588.39303.c9.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The small-diameter tumors might develop tumor thrombi in a shorter time and therefore have more aggressive genomic characteristics than larger ones. We aimed to explore the genomic features of this population and develop a grading system to improve the prediction of survival and drug efficacy in kidney cancer and pan-cancer patients. METHODS: In the development stage, rigorously filtered small diameter (<7 cm, equivalent to pT1 stage) clear cell renal cell carcinoma (ccRCC) patients with tumor thrombi were assigned to the high-risk group, and an equal number of regular pT1 ccRCC patients with the same tumor grade were randomly selected as the control group. Whole-exome sequencing (WES) was applied to normal-tumor-thrombus triples in the high-risk group and normal-tumor pairs in the control group. Multigene panels were generated based on the differences in genomic characteristics between the two groups. RESULTS: Compared with regular pT1 ccRCC patients with the same primary tumor diameter and grade, patients with tumor thrombi presented significant genomic heterogeneity in terms of somatic mutations, copy number variations (CNVs), and driver genes. In the TCGA and PAWG (Pan-cancer Analysis of Whole Genomes) validation, multigene dichotomous (altered vs. unaltered) panels presented good prediction effects for overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), homologous recombination deficiency (HRD), tumor mutation burden (TMB), microsatellite instability (MSI) and non-surgical first therapy response (NSFTR). If the common clinical critical indicators are used as golden standard (HRD ≥42, TMB ≥10/Mb, MSI sensor score ≥10) for verification, Panel 3 has excellent sensitivity (97.3%-100%) and negative predictive value (98.9%-100%) for predicting the efficacy of PARP inhibitors, cisplatin-based chemotherapy and immunotherapy. CONCLUSIONS: There are unique genomic characteristics in small-diameter ccRCC patients with tumor thrombi, which may be the reason for thrombus formation and poor clinical prognosis. Based on this, our study explored clinical panels for prognostic and drug sensitivity prediction, providing an accurate and individualized risk assessment beyond existing clinical parameters. Download PPT Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e139 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Chenghao Tan More articles by this author Shiming He More articles by this author Xuesong Li More articles by this author Sainan Zhu More articles by this author Ninghan Feng More articles by this author Qun He More articles by this author Libo Liu More articles by this author Zhisong He More articles by this author Liqun Zhou More articles by this author Gengyan Xiong More articles by this author Expand All Advertisement PDF downloadLoading ...