Universität zu Köln

Steenbock, Olivia ORCID: 0009-0002-7208-8104, Paffenholz, Pia ORCID: 0000-0002-8209-7795, Rieger, Constantin ORCID: 0009-0000-3993-7974, Heidenreich, Julian ORCID: 0009-0001-7556-7445, Pfister, David, von Brandenstein, Melanie ORCID: 0000-0002-1499-7644 and Heidenreich, Axel ORCID: 0000-0002-2511-3664 (2025). NGS-basierte („next generation sequencing“) molekulare Panelanalyse des metastasierten Prostatakarzinoms: Wie häufig finden wir therapierbare Mutationen? Die Urologie, 64 (3). pp. 256-268. Springer Nature. ISSN 2731-7064

PDF s00120-024-02493-2.pdf Bereitstellung unter der CC-Lizenz: Creative Commons Attribution. Download (548kB)

Abstract

Abstract Introduction Prostate cancer guidelines recommend molecular analysis of biomaterial following resistance to first-line systemic therapy in order to identify druggable mutations. We report on our results of molecular analysis of tissue specimens via next generation sequencing (NGS) in men with metastatic castration resistant prostate cancer (mCRPC). Patients and methods In all, 311 mCRPC patients underwent NGS analysis from biopsy samples of progressive metastatic lesions or archival radical prostatectomy specimens. NGS analysis was either performed using a panel of 18 prostate cancer-specific amplicons or via the TS0500 panel. Results Of the 311 biopsies, 299 (96%) revealed sufficient DNA content for NGS analysis independent on the specimen origin. Biopsies were taken from prostate (31%), lymph nodes (26%), visceral (17%) or osseous (18%) metastases. In 223 (75%) and 76 (25%) patients activating/inhibiting and no mutations were identified, respectively. Most frequently, mutations of HRD genes including a positive HRD score and p53 were identified in 22% of patients each. About 50% of HRD gene mutations were pathogenic and treatment with PARP inhibitors was initiated. Although the majority of p53 alterations were inactivating mutations, 3 patients demonstrated gain-of-function mutations resulting in an inactivation of ATM. Activating androgen receptor mutations and inactivating PTEN mutations were identified in 42 (14%) and 24 (8%) patients, respectively. Specific AR mutations resulted in a switch of hormonal therapy. Mutations of mismatch repair deficiency genes/MSI high were identified in 5 patients resulting in the administration of pembrolizumab. Addition of the TSO 500 panel identified additional mutations in 4.5% of patients and only 2% of the total cohort would have benefitted from this large panel with the identification of druggable mutations. Conclusion Druggable mutations were identified in one third of mCRPC patients using an 18 amplicon-panel analyzed via NGS. Based on our data, molecular analysis of AR mutations or mutations of the HRD genes should be performed following progression after first-line hormonal therapy. A more extensive molecular analysis seems to be useful following progression to the standard sequential hormonal, cytotoxicand radioligand therapies. Use of the expensive TSO 500 panel seems to be of additional therapeutic value in only a minority of patients.

Item Type:	Article
Translated title:	Title Language Next generation sequencing (NGS)-based molecular panel analysis for metastatic prostate cancer: how often can we detect druggable mutations?: NGS for metastatic adenocarcinoma of the prostate English
Creators:	Creators Email ORCID ORCID Put Code Steenbock, Olivia UNSPECIFIED https://orcid.org/0009-0002-7208-8104 UNSPECIFIED Paffenholz, Pia UNSPECIFIED https://orcid.org/0000-0002-8209-7795 UNSPECIFIED Rieger, Constantin UNSPECIFIED https://orcid.org/0009-0000-3993-7974 UNSPECIFIED Heidenreich, Julian UNSPECIFIED https://orcid.org/0009-0001-7556-7445 UNSPECIFIED Pfister, David UNSPECIFIED UNSPECIFIED UNSPECIFIED von Brandenstein, Melanie UNSPECIFIED https://orcid.org/0000-0002-1499-7644 UNSPECIFIED Heidenreich, Axel UNSPECIFIED https://orcid.org/0000-0002-2511-3664 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-797901
Identification Number:	10.1007/s00120-024-02493-2
Journal or Publication Title:	Die Urologie
Volume:	64
Number:	3
Page Range:	pp. 256-268
Number of Pages:	13
Date:	21 March 2025
Publisher:	Springer Nature
ISSN:	2731-7064
Language:	German
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Pathologie und Neuropathologie > Institut für Pathologie Faculty of Medicine > Urologie > Klinik und Poliklinik für Urologie
Subjects:	Medical sciences Medicine
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/79790