Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/168079
Title: Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers
Author: 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
Cardoso, Marta
Azzabi, Ashraf
Domchek, Susan
Lam, Jimmy
Taylor, Louise
Ronlund, Karina
Ramón y Cajal, Teresa
Salinas Masdeu, Mònica
Feliubadaló i Elorza, Maria Lídia
Rhiem, Kerstin
Gallagher, David
Cook, Jackie
Foulkes, William D.
Powers, Jacquelyn
Buys, Saundra S.
Halliday, Dorothy
Tischkowitz, Marc
Van Randeraad, Heleen
O'toole, Karen
Izatt, Louise
Susman, Rachel
Greenhalgh, Lynn
Carlsson, Stefan
Tripathi, Vishakha
Williams, Rachel
Aprikian, Armen
Walker, Lisa
Davidson, Rosemarie
Longmuir, Mark
Murthy, Vedang
Van Os, Theo A.
Ruijs, Mariëlle W. G.
Chen Shtoyerman, Rakefet
Helderman Van Den Enden, Apollonia T. J. M.
Donaldson, Alan
Andrews, Lesley
Murphy, Declan G.
Zgajnar, Janez
Jobson, Irene
Morton, Catherine
Shackleton, Kylie
Snape, Katie
Hamdy, Freddie C.
Mcgrath, John
Hanson, Helen
Harris, Marion
Taylor, Amy
Kast, Karin
Kirk, Judy
Johannsson, Oskar
Spigelman, Allan
Pachter, Nicholas
Cooke, Peter
Rothwell, Jeanette
Barwell, Julian
Brewer, Carole
Richardson, Kate
Tricker, Karen
Mikropoulos, Christos
Gadea, Neus
Brady, Angela F.
Copakova, Lucia
Foster, Christopher
Teo, Soo H.
Nicolai, Nicola
Friedman, Eitan
Offman, Judith
Axcrona, Karol
Obeid, Elias
Dudderidge, Tim
Henderson, Alex
Moynihan, Clare
Saya, Sibel
Gronberg, Henrik
Castro, Elena
Arun, Banu K.
IMPACT Study Collaborators
Eyfjord, Joruun
Dias, Alexander
Aaronson, Neil K.
Ong, Kay Ren
Lilja, Hans
Ardern Jones, Audrey
Bangma, Chris H.
Mckinley, Joanne
Dearnaley, David
Eccles, Diana
Cybulski, Cezary
Falconer, Alison
Stefansdottir, Vigdis
Eeles, Rosalind A.
Kiemeney, Lambertus A. L. M.
Rennert, Gadi
Maehle, Lovise
Khoo, Vincent
Van Zelst Stams, Wendy
Helfand, Brian T.
Lindeman, Geoffrey J.
Lubinski, Jan
Kote-Jarai, Zsofia
Mitra, Anita
James, Paul
Suri, Mohnish
Wilson, Penny
Schmutzler, Rita K.
Oosterwijk, Jan C.
Ausems, Margreet G. E. M.
Grindedal, Eli Marie
Rosario, Derek J.
Vickers, Andrew
Wokolorczyk, Dominika
Ringelberg, Janneke
Mascarenhas, Lyon
Genova, Elena
Side, Lucy
Thomas, Tessy
Adank, Muriel
Teixeira, Manuel R.
Van Asperen, Christi
Vasen, Hans
Ahmed, Munaza
Jensen, Thomas Dyrsø
Osther, Palle J. S.
Liljegren, Annelie
Oldenburg, Rogier A.
Huber, Camilla
Keywords: Càncer de pròstata
Mutació (Biologia)
Prostate cancer
Mutation (Biology)
Issue Date: 1-Dec-2019
Publisher: Elsevier
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.
Note: Reproducció del document publicat a: https://doi.org/10.1016/j.eururo.2019.08.019
It is part of: European Urology, 2019-12-01, vol. 76, num. 6, p. 831-842
URI: http://hdl.handle.net/2445/168079
Related resource: https://doi.org/10.1016/j.eururo.2019.08.019
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Files in This Item:
File Description SizeFormat 
PageEC.pdf5.54 kBAdobe PDFView/Open


This item is licensed under a Creative Commons License Creative Commons