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dc.contributor.authorPage, EC
dc.contributor.authorBancroft, EK
dc.contributor.authorBrook, MN
dc.contributor.authorAssel, M
dc.contributor.authorHassan Al Battat, M
dc.contributor.authorThomas, S
dc.contributor.authorTaylor, N
dc.contributor.authorChamberlain, A
dc.contributor.authorPope, J
dc.contributor.authorRaghallaigh, HN
dc.contributor.authorEvans, DG
dc.contributor.authorRothwell, J
dc.contributor.authorMaehle, L
dc.contributor.authorGrindedal, EM
dc.contributor.authorJames, P
dc.contributor.authorMascarenhas, L
dc.contributor.authorMcKinley, J
dc.contributor.authorSide, L
dc.contributor.authorThomas, T
dc.contributor.authorvan Asperen, C
dc.contributor.authorVasen, H
dc.contributor.authorKiemeney, LA
dc.contributor.authorRingelberg, J
dc.contributor.authorJensen, TD
dc.contributor.authorOsther, PJS
dc.contributor.authorHelfand, BT
dc.contributor.authorGenova, E
dc.contributor.authorOldenburg, RA
dc.contributor.authorCybulski, C
dc.contributor.authorWokolorczyk, D
dc.contributor.authorOng, K-R
dc.contributor.authorHuber, C
dc.contributor.authorLam, J
dc.contributor.authorTaylor, L
dc.contributor.authorSalinas, M
dc.contributor.authorFeliubadaló, L
dc.contributor.authorOosterwijk, JC
dc.contributor.authorvan Zelst-Stams, W
dc.contributor.authorCook, J
dc.contributor.authorRosario, DJ
dc.contributor.authorDomchek, S
dc.contributor.authorPowers, J
dc.contributor.authorBuys, S
dc.contributor.authorO'Toole, K
dc.contributor.authorAusems, MGEM
dc.contributor.authorSchmutzler, RK
dc.contributor.authorRhiem, K
dc.contributor.authorIzatt, L
dc.contributor.authorTripathi, V
dc.contributor.authorTeixeira, MR
dc.contributor.authorCardoso, M
dc.contributor.authorFoulkes, WD
dc.contributor.authorAprikian, A
dc.contributor.authorvan Randeraad, H
dc.contributor.authorDavidson, R
dc.contributor.authorLongmuir, M
dc.contributor.authorRuijs, MWG
dc.contributor.authorHelderman van den Enden, ATJM
dc.contributor.authorAdank, M
dc.contributor.authorWilliams, R
dc.contributor.authorAndrews, L
dc.contributor.authorMurphy, DG
dc.contributor.authorHalliday, D
dc.contributor.authorWalker, L
dc.contributor.authorLiljegren, A
dc.contributor.authorCarlsson, S
dc.contributor.authorAzzabi, A
dc.contributor.authorJobson, I
dc.contributor.authorMorton, C
dc.contributor.authorShackleton, K
dc.contributor.authorSnape, K
dc.contributor.authorHanson, H
dc.contributor.authorHarris, M
dc.contributor.authorTischkowitz, M
dc.contributor.authorTaylor, A
dc.contributor.authorKirk, J
dc.contributor.authorSusman, R
dc.contributor.authorChen-Shtoyerman, R
dc.contributor.authorSpigelman, A
dc.contributor.authorPachter, N
dc.contributor.authorAhmed, M
dc.contributor.authorRamon Y Cajal, T
dc.contributor.authorZgajnar, J
dc.contributor.authorBrewer, C
dc.contributor.authorGadea, N
dc.contributor.authorBrady, AF
dc.contributor.authorvan Os, T
dc.contributor.authorGallagher, D
dc.contributor.authorJohannsson, O
dc.contributor.authorDonaldson, A
dc.contributor.authorBarwell, J
dc.contributor.authorNicolai, N
dc.contributor.authorFriedman, E
dc.contributor.authorObeid, E
dc.contributor.authorGreenhalgh, L
dc.contributor.authorMurthy, V
dc.contributor.authorCopakova, L
dc.contributor.authorSaya, S
dc.contributor.authorMcGrath, J
dc.contributor.authorCooke, P
dc.contributor.authorRønlund, K
dc.contributor.authorRichardson, K
dc.contributor.authorHenderson, A
dc.contributor.authorTeo, SH
dc.contributor.authorArun, B
dc.contributor.authorKast, K
dc.contributor.authorDias, A
dc.contributor.authorAaronson, NK
dc.contributor.authorArdern-Jones, A
dc.contributor.authorBangma, CH
dc.contributor.authorCastro, E
dc.contributor.authorDearnaley, D
dc.contributor.authorEccles, DM
dc.contributor.authorTricker, K
dc.contributor.authorEyfjord, J
dc.contributor.authorFalconer, A
dc.contributor.authorFoster, C
dc.contributor.authorGronberg, H
dc.contributor.authorHamdy, FC
dc.contributor.authorStefansdottir, V
dc.contributor.authorKhoo, V
dc.contributor.authorLindeman, GJ
dc.contributor.authorLubinski, J
dc.contributor.authorAxcrona, K
dc.contributor.authorMikropoulos, C
dc.contributor.authorMitra, A
dc.contributor.authorMoynihan, C
dc.contributor.authorRennert, G
dc.contributor.authorSuri, M
dc.contributor.authorWilson, P
dc.contributor.authorDudderidge, T
dc.contributor.authorIMPACT Study Collaborators
dc.contributor.authorOffman, J
dc.contributor.authorKote-Jarai, Z
dc.contributor.authorVickers, A
dc.contributor.authorLilja, H
dc.contributor.authorEeles, RA
dc.date.accessioned2019-12-05T12:15:20Z
dc.date.issued2019-12
dc.identifier.citationEuropean urology, 2019, 76 (6), pp. 831 - 842
dc.identifier.issn0302-2838
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3433
dc.identifier.eissn1873-7560
dc.identifier.doi10.1016/j.eururo.2019.08.019
dc.description.abstractBackground 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.
dc.formatPrint-Electronic
dc.format.extent831 - 842
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectIMPACT Study Collaborators
dc.subjectHumans
dc.subjectProstatic Neoplasms
dc.subjectKallikreins
dc.subjectProstate-Specific Antigen
dc.subjectProspective Studies
dc.subjectGerm-Line Mutation
dc.subjectGenes, BRCA1
dc.subjectGenes, BRCA2
dc.subjectAdult
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectMale
dc.subjectEarly Detection of Cancer
dc.subjectGenetic Carrier Screening
dc.titleInterim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers.
dc.typeJournal Article
dcterms.dateAccepted2019-08-12
rioxxterms.versionofrecord10.1016/j.eururo.2019.08.019
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
rioxxterms.licenseref.startdate2019-12
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfEuropean urology
pubs.declined2019-09-20T10:59:00.951+0100
pubs.issue6
pubs.notesNo embargo
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Clinical Academic Radiotherapy (Dearnaley)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Clinical Academic Radiotherapy (Dearnaley)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics
pubs.publication-statusPublished
pubs.volume76
pubs.embargo.termsNo embargo
icr.researchteamClinical Academic Radiotherapy (Dearnaley)en_US
icr.researchteamOncogeneticsen_US
dc.contributor.icrauthorBrook, Marken
dc.contributor.icrauthorDearnaley, Daviden
dc.contributor.icrauthorKote-Jarai, Zsofiaen


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