Merseburger, Axel S., Waldron, Nick, Ribal, Maria J. ORCID: 0000-0001-8142-5382, Heidenreich, Axel, Perner, Sven, Fizazi, Karim, Sternberg, Cora N., Mateo, Joaquin, Wirth, Manfred P., Castro, Elena ORCID: 0000-0002-3691-6454, Olmos, David, Petrylak, Daniel P. and Chowdhury, Simon (2021). Genomic Testing in Patients with Metastatic Castration-resistant Prostate Cancer: A Pragmatic Guide for Clinicians. Eur. Urol., 79 (4). S. 519 - 530. AMSTERDAM: ELSEVIER. ISSN 1873-7560

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Abstract

Context: Genomic testing is becoming increasingly important in patients with advanced prostate cancer (PC) and is being incorporated in clinical practice to guide treatment. Objective: To review the current understanding of genomic alterations and the status of genomic testing in patients with metastatic castration-resistant PC (mCRPC), and the potential use of genomic tests in clinical practice. Evidence acquisition: We reviewed recent publications (past 15 yr) from PubMed, proceedings of scientific conferences, and published guidelines. Reports on mCRPC in the following areas were selected: development, testing, and validation of techniques for identifying genomic alterations; molecular characterization; and trials of genetically targeted therapies. Evidence synthesis: mCRPC tumors harbor molecular alterations that are possible targets for treatment, and a number of therapies are in development to exploit these alterations (eg, PD-1 inhibitors, PARP inhibitors, tyrosine kinase inhibitors). Next-generation sequencing of DNA from tumor tissue can identify somatic alterations that would not be identified by germline testing. Work is ongoing to evaluate the use of less invasive somatic testing methods (eg, sequencing of cell-free circulating tumor DNA). Current international guidelines recommend germline and/or somatic testing for men with advanced and/or high-risk PC regardless of family history to identify those with homologous recombination repair gene mutations or mismatch repair defects/microsatellite instability who may be eligible for treatment with a PARP inhibitor or pembrolizumab, respectively. Conclusions: Genomic testing for mCRPC may provide information on prognostic, predictive, and resistance biomarkers. Although the incorporation of testing into clinical practice remains challenging, routine genomic testing of men with advanced PC is recommended to guide management and treatment decisions. Patient summary: Similar to many cancers, prostate cancer is caused by defects in the cancer's DNA, which are called genetic or genomic defects. New treatments targeting these defects are approved for metastatic castration-resistant prostate cancer. Specific new tests are under development to detect these potentially treatable genetic defects. (C) 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Merseburger, Axel S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Waldron, NickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ribal, Maria J.UNSPECIFIEDorcid.org/0000-0001-8142-5382UNSPECIFIED
Heidenreich, AxelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perner, SvenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fizazi, KarimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sternberg, Cora N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mateo, JoaquinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wirth, Manfred P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Castro, ElenaUNSPECIFIEDorcid.org/0000-0002-3691-6454UNSPECIFIED
Olmos, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Petrylak, Daniel P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chowdhury, SimonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-603752
DOI: 10.1016/j.eururo.2020.12.039
Journal or Publication Title: Eur. Urol.
Volume: 79
Number: 4
Page Range: S. 519 - 530
Date: 2021
Publisher: ELSEVIER
Place of Publication: AMSTERDAM
ISSN: 1873-7560
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CELL-FREE DNA; GENE ABERRATIONS; PHASE-III; ENZALUTAMIDE; ABIRATERONE; MUTATIONS; TUMORS; MULTICENTER; BIOMARKERS; MANAGEMENTMultiple languages
Urology & NephrologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60375

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