Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in <i>BRCA2</i> Mutation Carriers

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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 et al (show 126 more authors) , Evans, D Gareth, Rothwell, Jeanette, Maehle, Lovise, Grindedal, Eli Marie, James, Paul, Mascarenhas, Lyon, McKinley, Joanne, Side, Lucy, Thomas, Tessy, van Asperen, Christi, Vasen, Hans, Kiemeney, Lambertus A, Ringelberg, Janneke, Jensen, Thomas Dyrso, Osther, Palle JS, 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, Oosterwijk, Jan C, van Zelst-Stams, Wendy, Cook, Jackie, Rosario, Derek J, Domchek, Susan, Powers, Jacquelyn, Buys, Saundra, O'Toole, Karen, Ausems, Margreet GEM, Schmutzler, Rita K, Rhiem, Kerstin, Izatt, Louise, Tripathi, Vishakha, Teixeira, Manuel R, Cardoso, Marta, Foulkes, William D, Aprikian, Armen, van Randeraad, Heleen, Davidson, Rosemarie, Longmuir, Mark, Ruijs, Marielle WG, Helderman van den Enden, Apollonia TJM, 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, Friedman, Eitan, Obeid, Elias, Greenhalgh, Lynn ORCID: 0000-0002-3141-7090, 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, 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, Axcrona, Karol, Mikropoulos, Christos, Mitra, Anita, Moynihan, Clare, Rennert, Gadi, Suri, Mohnish, Wilson, Penny, Dudderidge, Tim, Offman, Judith, 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 <i>BRCA2</i> Mutation Carriers. EUROPEAN UROLOGY, 76 (6). pp. 831-842.

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Abstract

<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Design, setting, and participants</h4>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.<h4>Outcome measurements and statistical analysis</h4>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.<h4>Results and limitations</h4>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).<h4>Conclusions</h4>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.<h4>Patient summary</h4>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.

Item Type:	Article
Uncontrolled Keywords:	BRCA1, BRCA2, Prostate-specific-antigen, Prostate cancer, Targeted prostate screening
Depositing User:	Symplectic Admin
Date Deposited:	28 Nov 2019 10:18
Last Modified:	14 Oct 2023 08:06
DOI:	10.1016/j.eururo.2019.08.019
Open Access URL:	https://doi.org/10.1016/j.eururo.2019.08.019
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3063829