Page, Elizabeth C., Bancroft, Elizabeth K., Brook, Mark N., Assel, Melissa, Al Battat, Mona Hassan, Thomas, Sarah, Taylor, Natalie, Chamberlain, Anthony, Pope, Jennifer, Ni Raghallaigh, Holly, Evans, D. Gareth, Rothwell, Jeanette, Maehle, Lovise, Grindedal, Eli Marie, James, Paul ORCID: 0000-0002-4361-4657, Mascarenhas, Lyon, McKinley, Joanne, Side, Lucy, Thomas, Tessy, van Asperen, Christi, Vasen, Hans, Kiemeney, Lambertus A., Ringelberg, Janneke, Jensen, Thomas Dyrso, Osther, Palle J. S., Helfand, Brian T., Genova, Elena, Oldenburg, Rogier A., Cybulski, Cezary, Wokolorczyk, Dominika, Ong, Kai-Ren, Huber, Camilla, Lam, Jimmy, Taylor, Louise, Salinas, Monica, Feliubadalo, Lidia ORCID: 0000-0002-1736-0112, Oosterwijk, Jan C., van Zelst-Stams, Wendy, Cook, Jackie, Rosario, Derek J., Domchek, Susan, Powers, Jacquelyn, Buys, Saundra, O'Toole, Karen, Ausems, Margreet G. E. M., Schmutzler, Rita K., Rhiem, Kerstin, Izatt, Louise, Tripathi, Vishakha, Teixeira, Manuel R., Cardoso, Marta ORCID: 0000-0002-3633-1659, Foulkes, William D., Aprikian, Armen, van Randeraad, Heleen, Davidson, Rosemarie, Longmuir, Mark, Ruijs, Marielle W. G., Helderman van den Enden, Apollonia T. J. M., Adank, Muriel, Williams, Rachel, Andrews, Lesley, Murphy, Declan G., Halliday, Dorothy, Walker, Lisa, Liljegren, Annelie, Carlsson, Stefan, Azzabi, Ashraf, Jobson, Irene, Morton, Catherine, Shackleton, Kylie, Snape, Katie, Hanson, Helen, Harris, Marion, Tischkowitz, Marc, Taylor, Amy, Kirk, Judy, Susman, Rachel, Chen-Shtoyerman, Rakefet, Spigelman, Allan, Pachter, Nicholas, Ahmed, Munaza, Ramon y Cajal, Teresa, Zgajnar, Janez, Brewer, Carole, Gadea, Neus, Brady, Angela F., van Os, Theo, Gallagher, David, Johannsson, Oskar, Donaldson, Alan, Barwell, Julian, Nicolai, Nicola ORCID: 0000-0002-5718-2699, Friedman, Eitan, Obeid, Elias, Greenhalgh, Lynn, Murthy, Vedang, Copakova, Lucia, Saya, Sibel, McGrath, John, Cooke, Peter, Ronlund, Karina, Richardson, Kate, Henderson, Alex, Teo, Soo H., Arun, Banu, Kast, Karin, Dias, Alexander, Aaronson, Neil K., Ardern-Jones, Audrey, Bangma, Chris H., Castro, Elena ORCID: 0000-0002-3691-6454, Dearnaley, David, Eccles, Diana M., Tricker, Karen, Eyfjord, Jorunn, Falconer, Alison, Foster, Christopher, Gronberg, Henrik, Hamdy, Freddie C., Stefansdottir, Vigdis, Khoo, Vincent, Lindeman, Geoffrey J., Lubinski, Jan ORCID: 0000-0003-2931-3003, Axcrona, Karol, Mikropoulos, Christos, Mitra, Anita, Moynihan, Clare, Rennert, Gadi, Suri, Mohnish, Wilson, Penny, Dudderidge, Tim, Offman, Judith ORCID: 0000-0001-5604-1635, Kote-Jarai, Zsofia, Vickers, Andrew, Lilja, Hans and Eeles, Rosalind A. (2019). Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers. Eur. Urol., 76 (6). S. 831 - 843. AMSTERDAM: ELSEVIER. ISSN 1873-7560

Full text not available from this repository.

Abstract

Background: Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) in men with germline BRCA1/2 mutations. Objective: To report the utility of PSA screening, PrCa incidence, positive predictive value of PSA, biopsy, and tumour characteristics after 3 yr of screening, by BRCA status. Design, setting, and participants: Men aged 40-69 yr with a germline pathogenic BRCA1/ 2 mutation and male controls testing negative for a familial BRCA1/2 mutation were recruited. Participants underwent PSA screening for 3 yr, and if PSA> 3.0 ng/ml, men were offered prostate biopsy. Outcome measurements and statistical analysis: PSA levels, PrCa incidence, and tumour characteristics were evaluated. Statistical analyses included Poisson regression offset by person-year follow-up, chi-square tests for proportion t tests for means, and Kruskal-Wallis for medians. Results and limitations: A total of 3027 patients (2932 unique individuals) were recruited (919 BRCA1 carriers, 709 BRCA1 noncarriers, 902 BRCA2 carriers, and 497 BRCA2 noncarriers). After 3 yr of screening, 527 men had PSA > 3.0 ng/ml, 357 biopsies were performed, and 112 PrCa cases were diagnosed (31 BRCA1 carriers, 19 BRCA1 noncarriers, 47 BRCA2 carriers, and 15 BRCA2 noncarriers). Higher compliance with biopsy was observed in BRCA2 carriers compared with noncarriers (73% vs 60%). Cancer incidence rate per 1000 person years was higher in BRCA2 carriers than in noncarriers (19.4 vs 12.0; p = 0.03); BRCA2 carriers were diagnosed at a younger age (61 vs 64 yr; p = 0.04) and were more likely to have clinically significant disease than BRCA2 noncarriers (77% vs 40%; p= 0.01). No differences in age or tumour characteristics were detected between BRCA1 carriers and BRCA1 noncarriers. The 4 kallikrein marker model discriminated better (area under the curve [AUC] = 0.73) for clinically significant cancer at biopsy than PSA alone (AUC = 0.65). Conclusions: After 3 yr of screening, compared with noncarriers, BRCA2 mutation carriers were associated with a higher incidence of PrCa, younger age of diagnosis, and clinically significant tumours. Therefore, systematic PSA screening is indicated for men with a BRCA2 mutation. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers. Patient summary: We demonstrate that after 3 yr of prostate-specific antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than in those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening. (C) 2019 The Authors. Published by Elsevier B.V.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Page, Elizabeth C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bancroft, Elizabeth K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brook, Mark N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Assel, MelissaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Al Battat, Mona HassanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomas, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Taylor, NatalieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chamberlain, AnthonyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pope, JenniferUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ni Raghallaigh, HollyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Evans, D. GarethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rothwell, JeanetteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maehle, LoviseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grindedal, Eli MarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
James, PaulUNSPECIFIEDorcid.org/0000-0002-4361-4657UNSPECIFIED
Mascarenhas, LyonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McKinley, JoanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Side, LucyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomas, TessyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Asperen, ChristiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vasen, HansUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kiemeney, Lambertus A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ringelberg, JannekeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jensen, Thomas DyrsoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Osther, Palle J. S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Helfand, Brian T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Genova, ElenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oldenburg, Rogier A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cybulski, CezaryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wokolorczyk, DominikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ong, Kai-RenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huber, CamillaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lam, JimmyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Taylor, LouiseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salinas, MonicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Feliubadalo, LidiaUNSPECIFIEDorcid.org/0000-0002-1736-0112UNSPECIFIED
Oosterwijk, Jan C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Zelst-Stams, WendyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cook, JackieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosario, Derek J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Domchek, SusanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Powers, JacquelynUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buys, SaundraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
O'Toole, KarenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ausems, Margreet G. E. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmutzler, Rita K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rhiem, KerstinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Izatt, LouiseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tripathi, VishakhaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teixeira, Manuel R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cardoso, MartaUNSPECIFIEDorcid.org/0000-0002-3633-1659UNSPECIFIED
Foulkes, William D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aprikian, ArmenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Randeraad, HeleenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Davidson, RosemarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Longmuir, MarkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruijs, Marielle W. G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Helderman van den Enden, Apollonia T. J. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Adank, MurielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Williams, RachelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Andrews, LesleyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Murphy, Declan G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Halliday, DorothyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Walker, LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liljegren, AnnelieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carlsson, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Azzabi, AshrafUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jobson, IreneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morton, CatherineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shackleton, KylieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Snape, KatieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hanson, HelenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Harris, MarionUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tischkowitz, MarcUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Taylor, AmyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kirk, JudyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Susman, RachelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chen-Shtoyerman, RakefetUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spigelman, AllanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pachter, NicholasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ahmed, MunazaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ramon y Cajal, TeresaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zgajnar, JanezUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brewer, CaroleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gadea, NeusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brady, Angela F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Os, TheoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gallagher, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Johannsson, OskarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Donaldson, AlanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barwell, JulianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nicolai, NicolaUNSPECIFIEDorcid.org/0000-0002-5718-2699UNSPECIFIED
Friedman, EitanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Obeid, EliasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Greenhalgh, LynnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Murthy, VedangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Copakova, LuciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saya, SibelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McGrath, JohnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cooke, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ronlund, KarinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Richardson, KateUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Henderson, AlexUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teo, Soo H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arun, BanuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kast, KarinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dias, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aaronson, Neil K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ardern-Jones, AudreyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bangma, Chris H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Castro, ElenaUNSPECIFIEDorcid.org/0000-0002-3691-6454UNSPECIFIED
Dearnaley, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eccles, Diana M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tricker, KarenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eyfjord, JorunnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Falconer, AlisonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Foster, ChristopherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gronberg, HenrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hamdy, Freddie C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stefansdottir, VigdisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Khoo, VincentUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lindeman, Geoffrey J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lubinski, JanUNSPECIFIEDorcid.org/0000-0003-2931-3003UNSPECIFIED
Axcrona, KarolUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mikropoulos, ChristosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mitra, AnitaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moynihan, ClareUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rennert, GadiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Suri, MohnishUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wilson, PennyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dudderidge, TimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Offman, JudithUNSPECIFIEDorcid.org/0000-0001-5604-1635UNSPECIFIED
Kote-Jarai, ZsofiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vickers, AndrewUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lilja, HansUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eeles, Rosalind A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-126568
DOI: 10.1016/j.eururo.2019.08.019
Journal or Publication Title: Eur. Urol.
Volume: 76
Number: 6
Page Range: S. 831 - 843
Date: 2019
Publisher: ELSEVIER
Place of Publication: AMSTERDAM
ISSN: 1873-7560
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CANCER MORTALITY; BREAST; TRIAL; MEN; PREDICTION; SURVIVAL; INCREASE; OVARIAN; ERSPCMultiple languages
Urology & NephrologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/12656

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