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Page EC , Bancroft EK , Brook MN , Assel M , Hassan Al Battat M , Thomas S , Taylor N , Chamberlain A , Pope J , Raghallaigh HN , Evans DG , Rothwell J , Maehle L , Grindedal EM , James P , Mascarenhas L , McKinley J , Side L , Thomas T , van Asperen C , Vasen H , Kiemeney LA , Ringelberg J , Jensen TD , Osther PJS , Helfand BT , Genova E , Oldenburg RA , Cybulski C , Wokolorczyk D , Ong KR , Huber C , Lam J , Taylor L , Salinas M , Feliubadalo L , Oosterwijk JC , van Zelst-Stams W , Cook J , Rosario DJ , Domchek S , Powers J , Buys S , O'Toole K , Ausems Mgem , Schmutzler RK , Rhiem K , Izatt L , Tripathi V , Teixeira MR , Cardoso M , Foulkes WD , Aprikian A , van Randeraad H , Davidson R , Longmuir M , Ruijs MWG , Helderman van den Enden Atjm , Adank M , Williams R , Andrews L , Murphy DG , Halliday D , Walker L , Liljegren A , Carlsson S , Azzabi A , Jobson I , Morton C , Shackleton K , Snape K , Hanson H , Harris M , Tischkowitz M , Taylor A , Kirk J , Susman R , Chen-Shtoyerman R , Spigelman A , Pachter N , Ahmed M , Ramon YCajal T , Zgajnar J , Brewer C , Gadea N , Brady AF , van Os T , Gallagher D , Johannsson O , Donaldson A , Barwell J , Nicolai N , Friedman E , Obeid E , Greenhalgh L , Murthy V , Copakova L , Saya S , McGrath J , Cooke P , Ronlund K , Richardson K , Henderson A , Teo SH , Arun B , Kast K , Dias A , Aaronson NK , Ardern-Jones A , Bangma CH , Castro E , Dearnaley D , Eccles DM , Tricker K , Eyfjord J , Falconer A , Foster C , Gronberg H , Hamdy FC , Stefansdottir V , Khoo V , Lindeman GJ , Lubinski J , Axcrona K , Mikropoulos C , Mitra A , Moynihan C , Rennert G , Suri M , Wilson P , Dudderidge T , Offman J , Kote-Jarai Z , Vickers A , Lilja H , Eeles RA
Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers
Eur Urol. 2019 Sep 16;76(6) :831-842
PMID: 31537406    PMCID: PMC6880781    URL: https://www.ncbi.nlm.nih.gov/pubmed/31537406
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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.
Notes
1873-7560 Page, Elizabeth C Bancroft, Elizabeth K Brook, Mark N Assel, Melissa Hassan Al Battat, Mona Thomas, Sarah Taylor, Natalie Chamberlain, Anthony Pope, Jennifer Raghallaigh, Holly Ni 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 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 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 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 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 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 IMPACT Study Collaborators Offman, Judith Kote-Jarai, Zsofia Vickers, Andrew Lilja, Hans Eeles, Rosalind A Journal Article Switzerland Eur Urol. 2019 Sep 16. pii: S0302-2838(19)30668-2. doi: 10.1016/j.eururo.2019.08.019.