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Title: | Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers |
Author: | Page, Elizabeth 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 Offman, Judith Axcrona, Karol Obeid, Elias Dudderidge, Tim Henderson, Alex Moynihan, Clare Eeles, Rosalind A. Saya, Sibel Gronberg, Henrik Castro, Elena Wilson, Penny Arun, Banu K. IMPACT Study Collaborators Eyfjord, Jorunn E. Dias, Alexander Aaronson, Neil K. Ong, Kai Ren Lilja, Hans Kiemeney, Lambertus A. L. M. Ardern Jones, Audrey Bangma, Chris H. Schmutzler, Rita K. Mckinley, Joanne Dearnaley, David Eccles, Diana Cybulski, Cezary Falconer, Alison Rennert, Gadi Maehle, Lovise Khoo, Vincent Van Zelst Stams, Wendy Helfand, Brian T. Oosterwijk, Jan C. Lindeman, Geoffrey J. Lubinski, Jan Cardoso, Marta Kote-Jarai, Zsofia Mitra, Anita James, Paul Suri, Mohnish Ausems, Margreet G. E. M. Grindedal, Eli Marie Rosario, Derek J. Azzabi, Ashraf Vickers, Andrew Wokolorczyk, Dominika Ringelberg, Janneke Halliday, Dorothy Mascarenhas, Lyon Genova, Elena Side, Lucy Thomas, Tessy Adank, Muriel A. Teixeira, Manuel R. Van Asperen, Christi Domchek, Susan Vasen, Hans Ahmed, Munaza Tischkowitz, Marc Jensen, Thomas Dyrsø Osther, Palle J. S. Liljegren, Annelie Oldenburg, Rogier A. Huber, Camilla Lam, Jimmy Taylor, Louise Ronlund, Karina Ramón y Cajal, Teresa Salinas Masdeu, Mònica Van Randeraad, Heleen Feliubadaló i Elorza, Maria Lídia Rhiem, Kerstin Gallagher, David Cook, Jackie Foulkes, William D. Powers, Jacquelyn Buys, Saundra S. O'toole, Karen Izatt, Louise Susman, Rachel Greenhalgh, Lynn Carlsson, Stefan Tripathi, Vishakha Williams, Rachel Cooke, Peter 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 Rothwell, Jeanette Andrews, Lesley Murphy, Declan G. Zgajnar, Janez Jobson, Irene Morton, Catherine Shackleton, Kylie Snape, Katie Hamdy, Freddie C. McGrath, John J. Hanson, Helen Barwell, Julian Harris, Marion Taylor, Amy Kast, Karin Kirk, Judy Johannsson, Oskar Spigelman, Allan Pachter, Nicholas Brewer, Carole Richardson, Kate Tricker, Karen Mikropoulos, Christos Gadea, Neus Brady, Angela F. Copakova, Lucia Stefansdottir, Vigdis Foster, Christopher Teo, Soo H. Nicolai, Nicola Friedman, Eitan |
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)) |
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