Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers
Por:
Page, EC, Bancroft, EK, Brook, MN, Assel, M, Al Battat, MH, Thomas, S, Taylor, N, Chamberlain, A, Pope, J, Ni Raghallaigh, H, 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, Cajal, TRY, 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, IMPACT Study Collaborators
Publicada:
1 dic 2019
Resumen:
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.
Filiaciones:
Page, EC:
Inst Canc Res, Oncogenet Team, London, England
Bancroft, EK:
Inst Canc Res, Oncogenet Team, London, England
Royal Marsden NHS Fdn Trust, Canc Genet Unit, London, England
Royal Marsden NHS Fdn Trust, Acad Urol Unit, London, England
Brook, MN:
Inst Canc Res, Oncogenet Team, London, England
Assel, M:
Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA
Al Battat, MH:
Lund Univ, Dept Translat Med, Malmo, Sweden
Thomas, S:
Royal Marsden NHS Fdn Trust, Canc Genet Unit, London, England
Royal Marsden NHS Fdn Trust, Acad Urol Unit, London, England
Taylor, N:
Royal Marsden NHS Fdn Trust, Canc Genet Unit, London, England
Royal Marsden NHS Fdn Trust, Acad Urol Unit, London, England
Chamberlain, A:
Inst Canc Res, Oncogenet Team, London, England
Pope, J:
Inst Canc Res, Oncogenet Team, London, England
Ni Raghallaigh, H:
Inst Canc Res, Oncogenet Team, London, England
Evans, DG:
Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Genet Med, Manchester, Lancs, England
Rothwell, J:
Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Genet Med, Manchester, Lancs, England
Maehle, L:
Oslo Univ Hosp, Dept Med Genet, N-0424 Oslo, Norway
Grindedal, EM:
Oslo Univ Hosp, Dept Med Genet, N-0424 Oslo, Norway
James, P:
Peter MacCallum Canc Ctr, Parkville Familial Canc Ctr, Melbourne, Vic, Australia
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia
Royal Melbourne Hosp, Genet Med, Parkville, Vic, Australia
Mascarenhas, L:
Peter MacCallum Canc Ctr, Parkville Familial Canc Ctr, Melbourne, Vic, Australia
McKinley, J:
Peter MacCallum Canc Ctr, Parkville Familial Canc Ctr, Melbourne, Vic, Australia
Side, L:
Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England
Thomas, T:
Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England
van Asperen, C:
Leiden Univ, Med Ctr, Leiden, Netherlands
Vasen, H:
Fdn Detect Hereditary Canc, Leiden, Netherlands
Kiemeney, LA:
Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands
Ringelberg, J:
Fdn Detect Hereditary Canc, Leiden, Netherlands
Jensen, TD:
Vejle Hosp, Dept Clin Genet, Vejle, Denmark
Osther, PJS:
Vejle Hosp, Dept Urol, Vejle, Denmark
Helfand, BT:
NorthShore Univ HlthSyst, Div Urol, John & Carol Walter Ctr Urol Hlth, Evanston, IL USA
Genova, E:
NorthShore Univ HlthSyst, Div Urol, John & Carol Walter Ctr Urol Hlth, Evanston, IL USA
Oldenburg, RA:
Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands
Cybulski, C:
Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland
Wokolorczyk, D:
Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland
Ong, KR:
Birmingham Womens Hosp, Clin Genet Unit, Birmingham, W Midlands, England
Huber, C:
Birmingham Womens Hosp, Clin Genet Unit, Birmingham, W Midlands, England
Lam, J:
Flinders Med Ctr, Dept Urol, Bedford Pk, SA, Australia
Taylor, L:
Repatriat Gen Hosp, Dept Urol, Daw Pk, SA, Australia
Salinas, M:
CIBERONC, Catalan Inst Oncol, ICO IDIBELL Bellvitge Biomed Res Inst, Hereditary Canc Program, Barcelona, Spain
Feliubadalo, L:
CIBERONC, Catalan Inst Oncol, ICO IDIBELL Bellvitge Biomed Res Inst, Hereditary Canc Program, Barcelona, Spain
Oosterwijk, JC:
Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands
van Zelst-Stams, W:
Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands
Cook, J:
Sheffield Childrens Hosp, Sheffield Clin Genet Serv, Sheffield, S Yorkshire, England
Rosario, DJ:
Royal Hallamshire Hosp, Sheffield, S Yorkshire, England
Domchek, S:
Univ Penn, Basser Res Ctr, Philadelphia, PA 19104 USA
Powers, J:
Univ Penn, Basser Res Ctr, Philadelphia, PA 19104 USA
Buys, S:
Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA
O'Toole, K:
Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA
Ausems, MGEM:
Univ Med Ctr, Dept Genet, Div Labs Pharm & Biomed Genet, Utrecht, Netherlands
Schmutzler, RK:
Univ Cologne, Fac Med, CIO, Ctr Familial Breast & Ovarian Canc, Cologne, Germany
Univ Hosp Cologne, Cologne, Germany
Rhiem, K:
Univ Cologne, Fac Med, CIO, Ctr Familial Breast & Ovarian Canc, Cologne, Germany
Univ Hosp Cologne, Cologne, Germany
Izatt, L:
Guys & St Thomas NHS Fdn Trust, Clin Genet Serv, London, England
Tripathi, V:
Guys & St Thomas NHS Fdn Trust, Clin Genet Serv, London, England
Teixeira, MR:
Portuguese Oncol Inst IPO Porto, Genet Dept, Porto, Portugal
Portuguese Oncol Inst IPO Porto, Res Ctr, Porto, Portugal
Univ Porto, Biomed Sci Inst ICBAS, Porto, Portugal
Cardoso, M:
Portuguese Oncol Inst IPO Porto, Genet Dept, Porto, Portugal
Portuguese Oncol Inst IPO Porto, Res Ctr, Porto, Portugal
Foulkes, WD:
McGill Univ, Hlth Ctr, Res Inst, Canc Res Program, Montreal, PQ, Canada
McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada
Aprikian, A:
McGill Univ, Hlth Ctr, Res Inst, Canc Res Program, Montreal, PQ, Canada
van Randeraad, H:
Fdn Detect Hereditary Canc, Leiden, Netherlands
Davidson, R:
Queen Elizabeth Univ Hosp, West Scotland Genet Serv, Glasgow, Lanark, Scotland
Longmuir, M:
Queen Elizabeth Univ Hosp, West Scotland Genet Serv, Glasgow, Lanark, Scotland
Ruijs, MWG:
Netherlands Canc Inst, Amsterdam, Netherlands
Helderman van den Enden, ATJM:
Maastricht Univ, Med Ctr, Dept Clin Genet, Maastricht, Netherlands
Adank, M:
Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands
Williams, R:
Univ New South Wales, Prince Wales Clin Sch, Fac Med, Sydney, NSW, Australia
Prince Wales Hosp, Hereditary Canc Ctr, Randwick, NSW, Australia
Andrews, L:
Univ New South Wales, Prince Wales Clin Sch, Fac Med, Sydney, NSW, Australia
Prince Wales Hosp, Hereditary Canc Ctr, Randwick, NSW, Australia
Murphy, DG:
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia
Peter MacCallum Canc Ctr, Div Canc Surg, Melbourne, Vic, Australia
Halliday, D:
Oxford Univ Hosp NHS Trust, Oxford Ctr Genom Med, Oxford, England
Walker, L:
Oxford Univ Hosp NHS Trust, Oxford Ctr Genom Med, Oxford, England
Liljegren, A:
Karolinska Univ Hosp, Stockholm, Sweden
Karolinska Inst, Stockholm, Sweden
Carlsson, S:
Karolinska Univ Hosp, Stockholm, Sweden
Karolinska Inst, Stockholm, Sweden
Azzabi, A:
Newcastle Upon Tyne Hosp, Northern Genet Serv, Newcastle Upon Tyne, Tyne & Wear, England
Jobson, I:
Newcastle Upon Tyne Hosp, Northern Genet Serv, Newcastle Upon Tyne, Tyne & Wear, England
Morton, C:
Royal Melbourne Hosp, Familial Canc Ctr, Grattan St, Parkville, Vic, Australia
Shackleton, K:
Royal Melbourne Hosp, Familial Canc Ctr, Grattan St, Parkville, Vic, Australia
Snape, K:
St George Hosp, London, England
Hanson, H:
St George Hosp, London, England
Harris, M:
Monash Hlth, Familial Canc Ctr, Clayton, Vic, Australia
Tischkowitz, M:
Cambridge Univ Hosp NHS Trust, East Anglian Med Genet Serv, Cambridge, England
Univ Cambridge, NIHR Cambridge Biomed Res Ctr, Acad Dept Med Genet, Level Addenbrookes Treatment Ctr 6, Cambridge Biomed Campus, Cambridge, England
Taylor, A:
Cambridge Univ Hosp NHS Trust, East Anglian Med Genet Serv, Cambridge, England
Kirk, J:
Westmead Hosp, Crown Princess Mary Canc Ctr, Familial Canc Serv, Sydney, NSW, Australia
Univ Sydney, Westmead Inst Med Res, Ctr Canc Res, Sydney Med Sch, Sydney, NSW, Australia
Susman, R:
Royal Brisbane & Womens Hosp, Genet Hlth Queensland, Herston, Qld, Australia
Chen-Shtoyerman, R:
Kaplan Med Ctr, Genet Inst, Rehovot, Israel
Spigelman, A:
Hunter Family Canc Serv, Waratah, NSW, Australia
Univ New South Wales, St Vincents Clin Sch, Sydney, NSW, Australia
St Vincents Hosp, Kinghorn Canc Ctr, Canc Genet Clin, Sydney, NSW, Australia
Pachter, N:
King Edward Mem Hosp, Genet Serv WA, Subiaco, WA, Australia
Univ Western Australia, Dept Paediat, Perth, WA, Australia
Ahmed, M:
Inst Child Hlth, NE Thames Reg Genet Serv, London, England
Cajal, TRY:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Zgajnar, J:
Inst Oncol, Ljubljana, Slovenia
Brewer, C:
Derriford Hosp, Peninsular Genet, Plymouth, Devon, England
Royal Devon & Exeter Hosp, Exeter, Devon, England
Gadea, N:
Hosp Valle De Hebron, Barcelona, Spain
Brady, AF:
London North West Univ Healthcare NHS Trust, Kennedy Galton Ctr, North West Thames Reg Genet Serv, Harrow, Middx, England
van Os, T:
Acad Med Ctr, Amsterdam, Netherlands
Gallagher, D:
St James Hosp, Dublin, Ireland
Johannsson, O:
Landspitali Natl Univ Hosp Iceland, Reykjavik, Iceland
Donaldson, A:
St Michaels Hosp, Bristol, Avon, England
Barwell, J:
Univ Leicester, Leicester, Leics, England
Univ Hosp Leicester, Leicester, Leics, England
Nicolai, N:
Ist Nazl Tumori, Milan, Italy
Friedman, E:
Chaim Shema Med Ctr, Tel Hashomer, Israel
Obeid, E:
Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA
Greenhalgh, L:
Liverpool Womens Hosp, Clin Genet Serv, Liverpool, Merseyside, England
Murthy, V:
Tata Mem Hosp, Mumbai, Maharashtra, India
Copakova, L:
Natl Canc Inst, Bratislava, Slovakia
Saya, S:
Inst Canc Res, Oncogenet Team, London, England
McGrath, J:
Royal Devon & Exeter Hosp, Exeter, Devon, England
Univ Exeter, Med Sch, St Lukes Campus, Exeter, Devon, England
Cooke, P:
New Cross Hosp, Wolverhampton, W Midlands, England
Ronlund, K:
Vejle Hosp, Dept Clin Genet, Vejle, Denmark
Richardson, K:
Peter MacCallum Canc Ctr, Parkville Familial Canc Ctr, Melbourne, Vic, Australia
Henderson, A:
Newcastle Upon Tyne Hosp, Northern Genet Serv, Newcastle Upon Tyne, Tyne & Wear, England
West Cumberland Infirm, Whitehaven, England
Teo, SH:
Subang Jaya Med Ctr, Canc Res Initiat Fdn, Selangor, Darul Ehsan, Malaysia
Arun, B:
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA
Kast, K:
Tech Univ Dresden, Med Fac, Dept Gynecol & Obstet, Dresden, Germany
Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dresden, Germany
Dias, A:
Inst Canc Res, Oncogenet Team, London, England
Inst Nacl Canc Jose de Alencar Gomes de Silva INC, Rio De Janeiro, Brazil
Aaronson, NK:
Netherlands Canc Inst, Amsterdam, Netherlands
Ardern-Jones, A:
Royal Marsden NHS Fdn Trust, Canc Genet Unit, London, England
Royal Marsden NHS Fdn Trust, Acad Urol Unit, London, England
Bangma, CH:
Erasmus MC, Dept Urol, Rotterdam, Netherlands
Castro, E:
Spanish Natl Canc Res Ctr, Madrid, Spain
Dearnaley, D:
Inst Canc Res, Div Radiotherapy & Imaging, Sutton, Surrey, England
Eccles, DM:
Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England
Univ Southampton, Med Sch, Southampton, Hants, England
Tricker, K:
Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Genet Med, Manchester, Lancs, England
Eyfjord, J:
Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland
Falconer, A:
Imperial Coll Healthcare NHS Trust, London, England
Foster, C:
HCA Pathol Labs, London, England
Gronberg, H:
Univ Hosp, Umea, Sweden
Hamdy, FC:
Churchill Hosp, Oxford, England
Univ Oxford, Nuffield Dept Surg Sci, Oxford, England
Stefansdottir, V:
Landspitali Natl Univ Hosp Iceland, Reykjavik, Iceland
Khoo, V:
Royal Marsden NHS Fdn Trust, Canc Genet Unit, London, England
Royal Marsden NHS Fdn Trust, Acad Urol Unit, London, England
St George Hosp, London, England
Inst Canc Res, Div Radiotherapy & Imaging, Sutton, Surrey, England
Univ Melbourne, Dept Med, Parkville, Vic, Australia
Lindeman, GJ:
Birmingham Womens Hosp, Clin Genet Unit, Birmingham, W Midlands, England
Univ Melbourne, Dept Med, Parkville, Vic, Australia
Walter & Eliza Hall Inst Med Res, Canc Biol & Stem Cells Div, Parkville, Vic, Australia
Lubinski, J:
Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland
Axcrona, K:
Akershus Univ Hosp, Dept Urol, Lorenskog, Norway
Mikropoulos, C:
Medway Hosp, Gillingham, Kent, England
Mitra, A:
Univ Coll London Hosp NHS Fdn Trust, London, England
Moynihan, C:
Inst Canc Res, Oncogenet Team, London, England
Rennert, G:
Carmel Hosp, CHS Natl Canc Control Ctr, Haifa, Israel
Suri, M:
Nottingham City Hosp, Nottingham, England
Wilson, P:
Innovate UK, Polaris House, Swindon, Wilts, England
Dudderidge, T:
Univ Hosp Southampton, Southampton, Hants, England
Offman, J:
Kings Coll London, Guys Hosp, Sch Canc & Pharmaceut Sci, Guys Canc Ctr,Fac Life Sci & Med, London, England
Kote-Jarai, Z:
Inst Canc Res, Oncogenet Team, London, England
Vickers, A:
Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA
Lilja, H:
Lund Univ, Dept Translat Med, Malmo, Sweden
Univ Oxford, Nuffield Dept Surg Sci, Oxford, England
Mem Sloan Kettering Canc Ctr, Dept Lab Med, 1275 York Ave, New York, NY 10021 USA
Mem Sloan Kettering Canc Ctr, Dept Surg, 1275 York Ave, New York, NY 10021 USA
Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA
Eeles, RA:
Inst Canc Res, Oncogenet Team, London, England
Royal Marsden NHS Fdn Trust, Canc Genet Unit, London, England
Royal Marsden NHS Fdn Trust, Acad Urol Unit, London, England
Green Published, Hybrid Gold, Green Accepted
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