{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:05:35Z","timestamp":1790190335738,"version":"4.1.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Austrian society for Urology and Andrology","award":["FA743A0601"],"award-info":[{"award-number":["FA743A0601"]}]},{"DOI":"10.13039\/501100005788","name":"Medical University of Vienna","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005788","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["World J Urol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Determining the frequency and distribution of pathogenic germline variants (PGVs) in Austrian prostate cancer (PCa) patients and to assess the accuracy of different clinical risk scores to correctly predict PGVs.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This cross-sectional study included 313 men with advanced PCa. A comprehensive personal and family history was obtained based on predefined questionnaires. Germline DNA sequencing was performed between 2019 and 2021 irrespective of family history, metastatic or castration status or age at diagnosis. Clinical risk scores for hereditary cancer syndromes were evaluated and a PCa-specific score was developed to assess the presence of PGVs.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>PGV presence was associated with metastasis (<jats:italic>p<\/jats:italic>\u2009=\u20090.047) and castration resistance (<jats:italic>p<\/jats:italic>\u2009=\u20090.011), but not with personal cancer history or with relatives with any type of cancer. Clinical risk scores (Manchester score, PREMM5 score, Amsterdam II criteria or Johns Hopkins criteria) showed low sensitivities (3.3\u201320%) for assessing the probability of PGV presence. A score specifically designed for PCa patients stratifying patients into low- or high-risk regarding PGV probability, correctly classified all PGV carriers as high-risk, whereas a third of PCa patients without PGVs was classified as low risk of the presence of PGVs.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Application of common clinical risk scores based on family history are not suitable to identify PCa patients with high PGV probabilities. A PCa-specific score stratified PCa patients into low- or high-risk of PGV presence with sufficient accuracy, and germline DNA sequencing may be omitted in patients with a low score. Further studies are needed to evaluate the score.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00345-023-04535-4","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T16:02:05Z","timestamp":1690905725000},"page":"2091-2097","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Performance of clinical risk scores and prediction models to identify pathogenic germline variants in patients with advanced prostate cancer"],"prefix":"10.1007","volume":"41","author":[{"given":"Katharina","family":"Rebhan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp D.","family":"Stelzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Pradere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawel","family":"Rajwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gero","family":"Kramer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Hofmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Resch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozan","family":"Yurdakul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco A.","family":"Laccone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Gerykova","family":"Bujalkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateja","family":"Smogavec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen Y.","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Ristl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahrokh F.","family":"Shariat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerda","family":"Egger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9496-4411","authenticated-orcid":false,"given":"Melanie R.","family":"Hassler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,1]]},"reference":[{"issue":"5","key":"4535_CR1","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1056\/NEJMoa1603144","volume":"375","author":"CC Pritchard","year":"2016","unstructured":"Pritchard CC, Mateo J, Walsh MF, De Sarkar N, Abida W, Beltran H et al (2016) Inherited DNA-repair gene mutations in men with metastatic prostate cancer. N Engl J Med 375(5):443\u2013453. https:\/\/doi.org\/10.1056\/NEJMoa1603144","journal-title":"N Engl J Med"},{"issue":"14","key":"4535_CR2","doi-asserted-by":"publisher","first-page":"1748","DOI":"10.1200\/JCO.2012.43.1882","volume":"31","author":"E Castro","year":"2013","unstructured":"Castro E, Goh C, Olmos D, Saunders E, Leongamornlert D, Tymrakiewicz M et al (2013) Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer. J Clin Oncol 31(14):1748\u20131757. https:\/\/doi.org\/10.1200\/JCO.2012.43.1882","journal-title":"J Clin Oncol"},{"issue":"2","key":"4535_CR3","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.eururo.2014.10.022","volume":"68","author":"E Castro","year":"2015","unstructured":"Castro E, Goh C, Leongamornlert D, Saunders E, Tymrakiewicz M, Dadaev T et al (2015) Effect of BRCA mutations on metastatic relapse and cause-specific survival after radical treatment for localised prostate cancer. Eur Urol 68(2):186\u2013193. https:\/\/doi.org\/10.1016\/j.eururo.2014.10.022","journal-title":"Eur Urol"},{"issue":"2","key":"4535_CR4","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1038\/sj.bjc.6604132","volume":"98","author":"A Mitra","year":"2008","unstructured":"Mitra A, Fisher C, Foster CS, Jameson C, Barbachanno Y, Bartlett J et al (2008) Prostate cancer in male BRCA1 and BRCA2 mutation carriers has a more aggressive phenotype. Br J Cancer 98(2):502\u2013507. https:\/\/doi.org\/10.1038\/sj.bjc.6604132","journal-title":"Br J Cancer"},{"key":"4535_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2019.12.003","author":"Y Wu","year":"2020","unstructured":"Wu Y, Yu H, Li S, Wiley K, Zheng SL, LaDuca H et al (2020) Rare germline pathogenic mutations of DNA repair genes are most strongly associated with grade group 5 prostate cancer. Eur Urol Oncol. https:\/\/doi.org\/10.1016\/j.euo.2019.12.003","journal-title":"Eur Urol Oncol"},{"key":"4535_CR6","doi-asserted-by":"publisher","first-page":"13671","DOI":"10.1038\/ncomms13671","volume":"8","author":"RA Taylor","year":"2017","unstructured":"Taylor RA, Fraser M, Livingstone J, Espiritu SM, Thorne H, Huang V et al (2017) Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories. Nat Commun 8:13671. https:\/\/doi.org\/10.1038\/ncomms13671","journal-title":"Nat Commun"},{"issue":"5 Suppl 2","key":"4535_CR7","first-page":"1","volume":"26","author":"LG Gomella","year":"2019","unstructured":"Gomella LG, Knudsen KE, Giri VN (2019) Introduction to the 2019 philadelphia prostate cancer consensus program: \u201cimplementation of genetic testing for inherited prostate cancer.\u201d Can J Urol 26(5 Suppl 2):1\u20134","journal-title":"Can J Urol"},{"issue":"2","key":"4535_CR8","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.eururo.2020.09.042","volume":"79","author":"N Mottet","year":"2021","unstructured":"Mottet N, van den Bergh RCN, Briers E, Van den Broeck T, Cumberbatch MG, De Santis M, et al (2021) EAU-EANM-ESTRO-ESUR-SIOG guidelines on prostate cancer-2020 update. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol 79(2):243\u2013262","journal-title":"Eur Urol"},{"key":"4535_CR9","unstructured":"National Comprehensive Cancer Network: Prostate Cancer, Verion 4.2019. https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/prostate.pdf. Accessed 19 Aug 2019"},{"issue":"6","key":"4535_CR10","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1136\/jmg.2003.017996","volume":"41","author":"DG Evans","year":"2004","unstructured":"Evans DG, Eccles DM, Rahman N, Young K, Bulman M, Amir E et al (2004) A new scoring system for the chances of identifying a BRCA1\/2 mutation outperforms existing models including BRCAPRO. J Med Genet 41(6):474\u2013480. https:\/\/doi.org\/10.1136\/jmg.2003.017996","journal-title":"J Med Genet"},{"issue":"6","key":"4535_CR11","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1016\/s0016-5085(99)70510-x","volume":"116","author":"HF Vasen","year":"1999","unstructured":"Vasen HF, Watson P, Mecklin JP, Lynch HT (1999) New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology 116(6):1453\u20131456. https:\/\/doi.org\/10.1016\/s0016-5085(99)70510-x","journal-title":"Gastroenterology"},{"issue":"19","key":"4535_CR12","doi-asserted-by":"publisher","first-page":"2165","DOI":"10.1200\/JCO.2016.69.6120","volume":"35","author":"F Kastrinos","year":"2017","unstructured":"Kastrinos F, Uno H, Ukaegbu C, Alvero C, McFarland A, Yurgelun MB et al (2017) Development and validation of the PREMM(5) model for comprehensive risk assessment of lynch syndrome. J Clin Oncol 35(19):2165\u20132172. https:\/\/doi.org\/10.1200\/JCO.2016.69.6120","journal-title":"J Clin Oncol"},{"issue":"3","key":"4535_CR13","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/s0022-5347(17)35617-3","volume":"150","author":"BS Carter","year":"1993","unstructured":"Carter BS, Bova GS, Beaty TH, Steinberg GD, Childs B, Isaacs WB et al (1993) Hereditary prostate cancer: epidemiologic and clinical features. J Urol 150(3):797\u2013802. https:\/\/doi.org\/10.1016\/s0022-5347(17)35617-3","journal-title":"J Urol"},{"issue":"4","key":"4535_CR14","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1001\/jamaoncol.2018.6760","volume":"5","author":"P Nicolosi","year":"2019","unstructured":"Nicolosi P, Ledet E, Yang S, Michalski S, Freschi B, O\u2019Leary E et al (2019) Prevalence of germline variants in prostate cancer and implications for current genetic testing guidelines. JAMA Oncol 5(4):523\u2013528. https:\/\/doi.org\/10.1001\/jamaoncol.2018.6760","journal-title":"JAMA Oncol"},{"issue":"4","key":"4535_CR15","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1001\/jamaoncol.2015.1313","volume":"1","author":"H Beltran","year":"2015","unstructured":"Beltran H, Eng K, Mosquera JM, Sigaras A, Romanel A, Rennert H et al (2015) Whole-exome sequencing of metastatic cancer and biomarkers of treatment response. JAMA Oncol 1(4):466\u2013474. https:\/\/doi.org\/10.1001\/jamaoncol.2015.1313","journal-title":"JAMA Oncol"},{"issue":"4","key":"4535_CR16","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1007\/s10689-010-9358-1","volume":"9","author":"YN You","year":"2010","unstructured":"You YN, Wolff BG, Boardman LA, Riegert-Johnson DL, Qin R (2010) Peutz-Jeghers syndrome: a study of long-term surgical morbidity and causes of mortality. Fam Cancer 9(4):609\u2013616. https:\/\/doi.org\/10.1007\/s10689-010-9358-1","journal-title":"Fam Cancer"},{"issue":"12","key":"4535_CR17","doi-asserted-by":"publisher","first-page":"1705","DOI":"10.1093\/annonc\/mdg486","volume":"14","author":"F Graziano","year":"2003","unstructured":"Graziano F, Humar B, Guilford P (2003) The role of the E-cadherin gene (CDH1) in diffuse gastric cancer susceptibility: from the laboratory to clinical practice. Ann Oncol 14(12):1705\u20131713. https:\/\/doi.org\/10.1093\/annonc\/mdg486","journal-title":"Ann Oncol"},{"issue":"5","key":"4535_CR18","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the Association for molecular pathology. Genet Med 17(5):405\u2013424. https:\/\/doi.org\/10.1038\/gim.2015.30","journal-title":"Genet Med"},{"key":"4535_CR19","doi-asserted-by":"publisher","DOI":"10.1200\/PO.16.00039","author":"VN Giri","year":"2017","unstructured":"Giri VN, Obeid E, Gross L, Bealin L, Hyatt C, Hegarty SE et al (2017) Inherited mutations in men undergoing multigene panel testing for prostate cancer: emerging implications for personalized prostate cancer genetic evaluation. JCO Precis Oncol. https:\/\/doi.org\/10.1200\/PO.16.00039","journal-title":"JCO Precis Oncol"},{"issue":"1","key":"4535_CR20","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.eururo.2017.02.023","volume":"72","author":"M Annala","year":"2017","unstructured":"Annala M, Struss WJ, Warner EW, Beja K, Vandekerkhove G, Wong A et al (2017) Treatment outcomes and tumor loss of heterozygosity in germline DNA repair-deficient prostate cancer. Eur Urol 72(1):34\u201342. https:\/\/doi.org\/10.1016\/j.eururo.2017.02.023","journal-title":"Eur Urol"},{"issue":"9","key":"4535_CR21","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1038\/s41436-020-0830-5","volume":"22","author":"M Pritzlaff","year":"2020","unstructured":"Pritzlaff M, Tian Y, Reineke P, Stuenkel AJ, Allen K, Gutierrez S et al (2020) Diagnosing hereditary cancer predisposition in men with prostate cancer. Genet Med 22(9):1517\u20131523. https:\/\/doi.org\/10.1038\/s41436-020-0830-5","journal-title":"Genet Med"},{"issue":"7","key":"4535_CR22","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1002\/pros.24120","volume":"81","author":"RA Sabol","year":"2021","unstructured":"Sabol RA, Ledet EM, Jaeger E, Hatton W, Moses M, Lankford A et al (2021) Family history and pathogenic\/likely pathogenic germline variants in prostate cancer patients. Prostate 81(7):427\u2013432. https:\/\/doi.org\/10.1002\/pros.24120","journal-title":"Prostate"},{"key":"4535_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/s41391-022-00609-3","author":"F Marino","year":"2022","unstructured":"Marino F, Totaro A, Gandi C, Bientinesi R, Moretto S, Gavi F et al (2022) Germline mutations in prostate cancer: a systematic review of the evidence for personalized medicine. Prostate Cancer Prostatic Dis. https:\/\/doi.org\/10.1038\/s41391-022-00609-3","journal-title":"Prostate Cancer Prostatic Dis"},{"issue":"1","key":"4535_CR24","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1038\/s41391-022-00618-2","volume":"26","author":"Z Wang","year":"2023","unstructured":"Wang Z, Yan X, Tang P, Tang T, Wang Y, Peng S et al (2023) Genetic profiling of hormone-sensitive and castration-resistant prostate cancers and identification of genetic mutations prone to castration-resistant prostate cancer. Prostate Cancer Prostatic Dis 26(1):180\u2013187. https:\/\/doi.org\/10.1038\/s41391-022-00618-2","journal-title":"Prostate Cancer Prostatic Dis"},{"issue":"3","key":"4535_CR25","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1038\/s41391-022-00517-6","volume":"25","author":"E Pan","year":"2022","unstructured":"Pan E, Shaya J, Madlensky L, Randall JM, Javier-Desloges J, Millard FE et al (2022) Germline alterations among Hispanic men with prostate cancer. Prostate Cancer Prostatic Dis 25(3):561\u2013567. https:\/\/doi.org\/10.1038\/s41391-022-00517-6","journal-title":"Prostate Cancer Prostatic Dis"},{"issue":"3","key":"4535_CR26","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1038\/s41391-021-00469-3","volume":"25","author":"N Weise","year":"2022","unstructured":"Weise N, Shaya J, Javier-Desloges J, Cheng HH, Madlensky L, McKay RR (2022) Disparities in germline testing among racial minorities with prostate cancer. Prostate Cancer Prostatic Dis 25(3):403\u2013410. https:\/\/doi.org\/10.1038\/s41391-021-00469-3","journal-title":"Prostate Cancer Prostatic Dis"}],"container-title":["World Journal of Urology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00345-023-04535-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00345-023-04535-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00345-023-04535-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T11:29:51Z","timestamp":1691666991000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00345-023-04535-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,1]]},"references-count":26,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["4535"],"URL":"https:\/\/doi.org\/10.1007\/s00345-023-04535-4","relation":{},"ISSN":["1433-8726"],"issn-type":[{"value":"1433-8726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,1]]},"assertion":[{"value":"25 March 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 June 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 August 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was approved by the local ethics committee (EK-Nr:\u00a01043\/2020, Ethics committee of the Medical University of Vienna).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}]}}