Page EC 1 , Bancroft EK 2 , Brook MN 1 , Assel M 3 , Hassan Al Battat M 4 , Thomas S 5 Show all authors , Taylor N 5 , Chamberlain A 1 , Pope J 1 , Raghallaigh HN 1 , Evans DG 6 , Rothwell J 6 , Maehle L 7 , Grindedal EM 7 , James P 8 , Mascarenhas L 9 , McKinley J 9 , Side L 10 , Thomas T 10 , van Asperen C 11 , Vasen H 12 , Kiemeney LA 13 , Ringelberg J 12 , Jensen TD 14 , Osther PJS 15 , Helfand BT 16 , Genova E 16 , Oldenburg RA 17 , Cybulski C 18 , Wokolorczyk D 18 , Ong KR 19 , Huber C 19 , Lam J 20 , Taylor L 21 , Salinas M 22 , Feliubadaló L 22 , Oosterwijk JC 23 , van Zelst-Stams W 13 , Cook J 24 , Rosario DJ 25 , Domchek S 26 , Powers J 26 , Buys S 27 , O'Toole K 27 , Ausems MGEM 28 , Schmutzler RK 29 , Rhiem K 29 , Izatt L 30 , Tripathi V 30 , Teixeira MR 31 , Cardoso M 32 , Foulkes WD 33 , Aprikian A 34 , van Randeraad H 12 , Davidson R 35 , Longmuir M 35 , Ruijs MWG 36 , Helderman van den Enden ATJM 37 , Adank M 38 , Williams R 39 , Andrews L 39 , Murphy DG 40 , Halliday D 41 , Walker L 41 , Liljegren A 42 , Carlsson S 42 , Azzabi A 43 , Jobson I 43 , Morton C 44 , Shackleton K 44 , Snape K 45 , Hanson H 45 , Harris M 46 , Tischkowitz M 47 , Taylor A 48 , Kirk J 49 , Susman R 50 , Chen-Shtoyerman R 51 , Spigelman A 52 , Pachter N 53 , Ahmed M 54 , Ramon Y Cajal T 55 , Zgajnar J 56 , Brewer C 57 , Gadea N 58 , Brady AF 59 , van Os T 60 , Gallagher D 61 , Johannsson O 62 , Donaldson A 63 , Barwell J 64 , Nicolai N 65 , Friedman E 66 , Obeid E 67 , Greenhalgh L 68 , Murthy V 69 , Copakova L 70 , Saya S 1 , McGrath J 71 , Cooke P 72 , Rønlund K 14 , Richardson K 9 , Henderson A 73 , Teo SH 74 , Arun B 75 , Kast K 76 , Dias A 77 , Aaronson NK 36 , Ardern-Jones A 5 , Bangma CH 78 , Castro E 79 , Dearnaley D 80 , Eccles DM 81 , Tricker K 6 , Eyfjord J 82 , Falconer A 83 , Foster C 84 , Gronberg H 85 , Hamdy FC 86 , Stefansdottir V 62 , Khoo V 87 , Lindeman GJ 88 , Lubinski J 18 , Axcrona K 89 , Mikropoulos C 90 , Mitra A 91 , Moynihan C 1 , Rennert G 92 , Suri M 93 , Wilson P 94 , Dudderidge T 95 , IMPACT Study Collaborators , Offman J 96 , Kote-Jarai Z 1 , Vickers A 3 , Lilja H 97 , Eeles RA 98

Affiliations 

  • 1 Oncogenetics Team, Institute of Cancer Research, London, UK
  • 2 Oncogenetics Team, Institute of Cancer Research, London, UK; Cancer Genetics Unit and Academic Urology Unit, Royal Marsden NHS Foundation Trust, London, UK
  • 3 Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY, USA
  • 4 Department of Translational Medicine, Lund University, Malmö, Sweden
  • 5 Cancer Genetics Unit and Academic Urology Unit, Royal Marsden NHS Foundation Trust, London, UK
  • 6 Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
  • 7 Department of medical genetics, Oslo University Hospital, 0424 Oslo, Norway
  • 8 Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, VIC, Australia; Genetic Medicine, The Royal Melbourne Hospital, Parkville, VIC, Australia
  • 9 Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  • 10 Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK
  • 11 Leiden University Medical Center, Leiden, The Netherlands
  • 12 The Foundation for the Detection of Hereditary Cancer, Leiden, The Netherlands
  • 13 Radboud University Medical Center, Nijmegen, The Netherlands
  • 14 Department of Clinical Genetics, Vejle Hospital, Vejle, Denmark
  • 15 Department of Urology, Vejle Hospital, Vejle, Denmark
  • 16 John and Carol Walter Center for Urological Health, Division of Urology, NorthShore University HealthSystem, Evanston, IL, USA
  • 17 Department of clinical genetics, Erasmus University Medical Center, Rotterdam, The Netherlands
  • 18 International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University in Szczecin, Szczecin, Poland
  • 19 Clinical Genetics Unit, Birmingham Women's Hospital, Birmingham, UK
  • 20 Department of Urology, Flinders Medical Centre, Bedford Park, SA, Australia
  • 21 Department of Urology, Repatriation General Hospital, Daw Park, SA, Australia
  • 22 Hereditary Cancer Program, ICO-IDIBELL (Bellvitge Biomedical Research Institute, Catalan Institute of Oncology), CIBERONC, Barcelona, Spain
  • 23 University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
  • 24 Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield, UK
  • 25 Royal Hallamshire Hospital, Sheffield, UK
  • 26 Basser Research Center, University of Pennsylvania, Philadelphia, PA, USA
  • 27 Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
  • 28 Division of Laboratories, Pharmacy and Biomedical Genetics, Department of Genetics, University Medical Centre, Utrecht, The Netherlands
  • 29 Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
  • 30 Clinical Genetics Service, Guy's and St Thomas' NHS Foundation Trust, London, UK
  • 31 Genetics Department and Research Center, Portuguese Oncology Institute (IPO Porto), Porto, Portugal; Biomedical Sciences Institute (ICBAS), Porto University, Porto, Portugal
  • 32 Genetics Department and Research Center, Portuguese Oncology Institute (IPO Porto), Porto, Portugal
  • 33 Cancer Research Program, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada; Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, QC, Canada
  • 34 Cancer Research Program, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada
  • 35 West of Scotland Genetic Service, Queen Elizabeth University Hospital, Glasgow, UK
  • 36 Netherlands Cancer Institute, Amsterdam, The Netherlands
  • 37 Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands
  • 38 VU University Medical Center, Amsterdam, The Netherlands
  • 39 Hereditary Cancer Centre, Prince of Wales Hospital, Randwick, NSW, Australia; Prince of Wales Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
  • 40 The Sir Peter MacCallum Department of Oncology, University of Melbourne, VIC, Australia; Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  • 41 Oxford Centre for Genomic Medicine, Oxford University Hospitals NHS Trust, Oxford, UK
  • 42 Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden
  • 43 Northern Genetics Service, Newcastle upon Tyne Hospitals, UK
  • 44 Familial Cancer Centre, The Royal Melbourne Hospital, Grattan St, Parkville, VIC, Australia
  • 45 St George's Hospital, Tooting, London, UK
  • 46 Familial Cancer Centre, Monash Health, Clayton, VIC, Australia
  • 47 East Anglian Medical Genetics Service, Cambridge University Hospitals NHS Trust, Cambridge, UK; Academic Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Level 6 Addenbrooke's Treatment Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK
  • 48 East Anglian Medical Genetics Service, Cambridge University Hospitals NHS Trust, Cambridge, UK
  • 49 Familial Cancer Service, Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, Sydney, NSW, Australia; Sydney Medical School, University of Sydney, Centre for Cancer Research, The Westmead Institute for Medical Research, Westmead, Sydney, NSW, Australia
  • 50 Genetic Health Queensland, Royal Brisbane & Women's Hospital, Herston, QLD, Australia
  • 51 The Genetic Institute, Kaplan Medical Center, Rehovot, Israel
  • 52 Hunter Family Cancer Service, Waratah, NSW, Australia; University of New South Wales, St Vincent's Clinical School, NSW, Australia; Cancer Genetics Clinic, The Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, NSW, Australia
  • 53 Genetic Services of WA, King Edward Memorial Hospital, Subiaco, WA, Australia; Department of Paediatrics, University of Western Australia, Perth, WA, Australia
  • 54 NE Thames Regional Genetics Service, Institute of Child Health, London, UK
  • 55 Hospital de Sant Pau, Barcelona, Spain
  • 56 Institute of Oncology, Ljubljana, Slovenia
  • 57 Peninsular Genetics, Derriford Hospital, Plymouth, UK; Royal Devon and Exeter Hospital, Exeter, UK
  • 58 Hospital Vall d'Hebron, Barcelona, Spain
  • 59 North West Thames Regional Genetics Service, Kennedy-Galton Centre, London North West University Healthcare NHS Trust, Harrow, UK
  • 60 Academic Medical Center, Amsterdam, The Netherlands
  • 61 St James's Hospital, Dublin, Ireland
  • 62 Landspitali-the National University Hospital of Iceland, Reykjavik, Iceland
  • 63 St Michael's Hospital, Bristol, UK
  • 64 University of Leicester, Leicester, UK; University Hospitals Leicester, Leicester, UK
  • 65 Istituto Nazionale dei Tumori, Milano, Italy
  • 66 Chaim Shema Medical Center, Tel-Hashomer, Israel
  • 67 Fox Chase Cancer Center, Philadelphia, PA, USA
  • 68 Clinical Genetics Service, Liverpool Women's Hospital, Liverpool, UK
  • 69 Tata Memorial Centre, Mumbai, India
  • 70 National Cancer Institute, Bratislava, Slovak Republic
  • 71 Royal Devon and Exeter Hospital, Exeter, UK; University of Exeter Medical School, St Luke's Campus, Exeter, UK
  • 72 New Cross Hospital, Wolverhampton, UK
  • 73 Northern Genetics Service, Newcastle upon Tyne Hospitals, UK; West Cumberland Infirmary, Whitehaven, UK
  • 74 Cancer Research Initiatives Foundation, Subang Jaya Medical Centre, Selangor, Darul Ehsan, Malaysia
  • 75 The University of Texas, MD Anderson Cancer Center, Houston, TX, USA
  • 76 Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
  • 77 Oncogenetics Team, Institute of Cancer Research, London, UK; Instituto Nacional de Cancer Jose de Alencar Gomes da Silva (INCA), Rio de Janeiro, Brazil
  • 78 Department of urology, Erasmus University Medical Center, Rotterdam, The Netherlands
  • 79 Spanish National Cancer Research Center, Madrid, Spain
  • 80 Division of Radiotherapy and Imaging, The Institute of Cancer Research, Sutton, UK
  • 81 The University of Southampton Medical School, Southampton, UK; Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK
  • 82 Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland
  • 83 Imperial College Healthcare NHS Trust, London, UK
  • 84 HCA Pathology Laboratories, London, UK
  • 85 University Hospital, Umea, Sweden
  • 86 Churchill Hospital, Headington, Oxford, UK; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
  • 87 Cancer Genetics Unit and Academic Urology Unit, Royal Marsden NHS Foundation Trust, London, UK; St George's Hospital, Tooting, London, UK; Division of Radiotherapy and Imaging, The Institute of Cancer Research, Sutton, UK; Department of Medicine, The University of Melbourne, Parkville, VIC, Australia
  • 88 Familial Cancer Centre, The Royal Melbourne Hospital, Grattan St, Parkville, VIC, Australia; Department of Medicine, The University of Melbourne, Parkville, VIC, Australia; Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  • 89 Department of Urology, Akershus University Hospital, Lørenskog, Norway
  • 90 Medway Hospital, Kent, UK
  • 91 University College London Hospitals NHS Foundation Trust, London, UK
  • 92 CHS National Cancer Control Center, Carmel Medical Center, Haifa, Israel
  • 93 Nottingham City Hospital, Nottingham, UK
  • 94 Innovate UK, Polaris House, Swindon, UK
  • 95 University Hospital Southampton, Southampton, UK
  • 96 School of Cancer and Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, King's College London, Guy's Cancer Centre, Guy's Hospital, London, UK
  • 97 Department of Translational Medicine, Lund University, Malmö, Sweden; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK; Departments of Laboratory Medicine, Surgery, and Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
  • 98 Oncogenetics Team, Institute of Cancer Research, London, UK; Cancer Genetics Unit and Academic Urology Unit, Royal Marsden NHS Foundation Trust, London, UK. Electronic address: rosalind.eeles@icr.ac.uk
Eur Urol, 2019 12;76(6):831-842.
PMID: 31537406 DOI: 10.1016/j.eururo.2019.08.019

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.