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Wir berichten \u00fcber unsere Ergebnisse der molekularen Diagnostik bei Patienten mit metastasiertem kastrationsresistenten PCA (mCRPC).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Patienten und Methodik<\/jats:title>\n            <jats:p>311 Patienten mit mCRPC erhielten eine molekulare Panelanalyse von archivierten Prostatektomiepr\u00e4paraten oder Computertomografie(CT)-gest\u00fctzten Biopsien progredienter Metastasen mittels standardisiertem NGS-Verfahren eines Panels von 18 spezifischen Mutationen bzw. dem TSO500-Panel.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Ergebnisse<\/jats:title>\n            <jats:p>Unabh\u00e4ngig vom Entnahmeort hatten 299\/311 (96\u202f%) der Biopsien einen ausreichenden DNA-Gehalt f\u00fcr das NGS. NGS erfolgte aus Prostata (31\u202f%), Lymphknoten (26\u202f%), viszeralen (17\u202f%) und oss\u00e4ren (18\u202f%) Metastasen. Bei 223 (75\u202f%) bzw. 76 (25\u202f%) Patienten wurden aktivierende\/inhibierende bzw. keine Mutationen identifiziert. Am h\u00e4ufigsten fanden sich Mutationen der HRD-Gene (BRCA 1\/2, ATM, CDK12, CHEK2, FANCA, Rad51C) sowie des p53 mit jeweils 22\u202f%. Die Mehrzahl der p53Mutationen waren inaktivierend, in 3 F\u00e4llen wurde eine Gain-of-function-Mutation identifiziert. Mutationen der HRD-Gene inklusive eines positiven HRD-Scores waren in &gt;\u202f50\u202f% pathogen, so dass PARP-Inhibitoren eingesetzt werden konnten. Aktivierende Androgenrezeptor \u2013 sowie inaktivierende PTEN\/aktivierende PIC3Ca-Mutationen fanden sich bei 42 (14\u202f%) bzw. 24 (8\u202f%) Patienten. Aufgrund der spezifischen AR-Mutationen wurde eine Therapieumstellung bei 14 Patienten vorgenommen. Mutationen der Mismatch-repair-deficiency-Gene\/MSI-high lagen in 3 F\u00e4llen vor, so dass Pembrolizumab appliziert werden konnte. Die Addition des TSO500-Panels identifizierte nur bei 4,5\u202f% der Patienten zus\u00e4tzliche Mutationen, bei nur 2\u202f% der Patienten h\u00e4tte diese eine therapeutische Implikation gehabt.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Schlussfolgerungen<\/jats:title>\n            <jats:p>Eine NGS-Analyse beim mCRPC zeigt bei einem Drittel der Patienten Mutationen auf, die bereits jetzt zielgerichtet therapierbar sind. Eine fundierte Analyse der HRD-Gene sowie von AR-Mutationen sollte nach Versagen der Erstlinientherapie erfolgen. Eine ausgedehnte molekulare Analyse empfiehlt sich nach Versagen der sequentiellen Standardtherapie. Die molekulare Analyse mittels des TSO500-Panels ist nur in wenigen F\u00e4llen zielf\u00fchrend.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Graphic abstract<\/jats:title>\n          <\/jats:sec>","DOI":"10.1007\/s00120-024-02493-2","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T12:07:14Z","timestamp":1737461234000},"page":"256-268","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["NGS-basierte (\u201enext generation sequencing\u201c) molekulare Panelanalyse des metastasierten Prostatakarzinoms: Wie h\u00e4ufig finden wir therapierbare Mutationen?","Next generation sequencing (NGS)-based molecular panel analysis for metastatic prostate cancer: how often can we detect druggable mutations?"],"prefix":"10.1007","volume":"64","author":[{"given":"Olivia","family":"Steenbock","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pia","family":"Paffenholz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Constantin","family":"Rieger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"Heidenreich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Pfister","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"von Brandenstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axel","family":"Heidenreich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,1,21]]},"reference":[{"unstructured":"https:\/\/www.krebsdaten.de","key":"2493_CR1"},{"issue":"10437","key":"2493_CR2","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1016\/S0140-6736(24)00651-2","volume":"403","author":"ND James","year":"2024","unstructured":"James\u00a0ND, Tannock\u00a0I, N\u2019Dow\u00a0J et\u00a0al (2024) Commission on prostate cancer: planning for the surge in cases. 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Ein positives Ethikvotum liegt vor (19-1274, 21-1155, 23-1124). Von allen beteiligten Patient\/-innen liegt eine Einverst\u00e4ndniserkl\u00e4rung vor.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Interessenkonflikt"}}]}}