Targeted Prostate Cancer Screening in Carriers of BRCA1 or BRCA2 Pathogenic Germline Variants Detects Clinically Relevant Disease: 5-year Results from the IMPACT Study

Elizabeth K Bancroft¹, Elizabeth C Page², Jana McHugh², Sarah Thomas³, Natalie Taylor³, Jennifer Pope², D Gareth Evans⁴, Jeanette Rothwell⁵, Eli Marie Grindedal⁶, Lovise Maehle⁶, Paul James⁷, Joanne McKinley⁸, Lyon Mascarenhas⁸, Lucy Side⁹, Tessy Thomas⁹, Monique E van Leerdam¹⁰, Christi J van Asperen¹¹, Lambertus A L M Kiemeney¹², Janneke Ringelberg¹³, Michiel Vlaming¹⁴, Karina Rønlund¹⁵, Palle J S Osther¹⁶, Brian T Helfand¹⁷, Christina G Hutten¹⁸, Rogier A Oldenburg¹⁹, Cezary Cybulski²⁰, Dominika Wokolorczyk²⁰, Kai-Ren Ong²¹, Camilla Huber²¹, Monica Salinas²², Lidia Feliubadaló²², Jan C Oosterwijk²³, Wendy A G van Zelst-Stams²⁴, Jackie Cook²⁵, Derek J Rosario²⁶, Kara Maxwell²⁷, Jacquelyn Powers²⁷, Saundra Buys²⁸, Jo Lyman²⁸, Margreet G E M Ausems¹⁴, Rita K Schmutzler²⁹, Kerstin Rhiem²⁹, Louise Izatt³⁰, Vishakha Tripathi³⁰, Manuel R Teixeira³¹, Marta Cardoso³², William D Foulkes³³, Armen Aprikian³⁴, Rosemarie Davidson³⁵, Mark Longmuir³⁵, Mariëlle W G Ruijs³⁶, Eveline W Blom³⁷, Klaartje van Engelen³⁸, Rachel Williams³⁹, Lesley Andrews⁴⁰, Declan G Murphy⁴¹, Sibel Saya⁴², Dorothy Halliday⁴³, Lisa Walker⁴³, Annelie Liljegren⁴⁴, Stefan Carlsson⁴⁴, Ashraf Azzabi⁴⁵, Irene Jobson⁴⁵, Katie Snape⁴⁶, Merrie Gowie⁴⁶, Marion Harris⁴⁷, Marc Tischkowitz⁴⁸, Amy Taylor⁴⁹, Judy Kirk⁵⁰, Rachel Susman⁵¹, Rakefet Chen-Shtoyerman⁵², Allan Spigelman⁵³, Nicholas Pachter⁵⁴, Munaza Ahmed⁵⁵, Teresa Ramon Y Cajal⁵⁶, Mateja Krajc⁵⁷, Ruth Cleaver⁵⁸, Mara Cruellas⁵⁹, Eduard Perez-Ballestero⁶⁰, Angela F Brady⁶¹, David Gallagher⁶², Alan Donaldson⁶³, Julian Barwell⁶⁴, Nicola Nicolai⁶⁵, Eitan Friedman⁶⁶, Michael J Hall⁶⁷, Lynn Greenhalgh⁶⁸, Vedang Murthy⁶⁹, Lucia Copakova⁷⁰, John S McGrath⁷¹, Peter Cooke⁷², Banu Arun⁷³, Kathryn Myhill³, Matthew Hogben³, Syed Hussain², Neil K Aaronson⁷⁴, Audrey Ardern-Jones³, Chris H Bangma⁷⁵, Elena Castro⁷⁶, David Dearnaley⁷⁷, Diana M Eccles⁷⁸, Karen Tricker⁵, Alison Falconer⁷⁹, Henrik Gronberg⁸⁰, Freddie C Hamdy⁸¹, Vincent Khoo⁸², Hans Lilja⁸³, Geoffrey J Lindeman⁸⁴, Jan Lubinski²⁰, Karol Axcrona⁸⁵, Christos Mikropoulos⁸⁶, Anita Mitra⁸⁷, Judith Offman⁸⁸, Gad Rennert⁸⁹, Mohnish Suri⁹⁰, Tim Dudderidge⁹¹; IMPACT Study Collaborators; Mark N Brook², Zsofia Kote-Jarai², Rosalind A Eeles⁹²

Affiliations

¹ Oncogenetics Team, Genetics and Epidemiology, The Institute of Cancer Research, London, UK; Cancer Genetics Unit and Academic Urology Unit, The Royal Marsden NHS Foundation Trust, London, UK.
² Oncogenetics Team, Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
³ Cancer Genetics Unit and Academic Urology Unit, The Royal Marsden NHS Foundation Trust, London, UK.
⁴ Department of Genomic Medicine, Division of Evolution, Infection and Genomic Sciences, University of Manchester, Manchester, UK.
⁵ Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
⁶ Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
⁷ Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Department of Genetic Medicine, Royal Melbourne Hospital, Parkville, Australia.
⁸ Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia.
⁹ Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK.
¹⁰ Dutch Foundation for Detection of Hereditary Tumors, Leiden, The Netherlands; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
¹¹ Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
¹² Radboud University Medical Center, Nijmegen, The Netherlands.
¹³ Dutch Foundation for Detection of Hereditary Tumors, Leiden, The Netherlands.
¹⁴ Department of Genetics, Division Laboratories, Pharmacy and Biomedical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands.
¹⁵ Department of Clinical Genetics, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark.
¹⁶ Department of Urology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark.
¹⁷ John and Carol Walter Center for Urological Health, Division of Urology, Endeavor Health NorthShore University HealthSystem, Evanston, IL, USA.
¹⁸ Internal Medicine Epidemiology, Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, IL, USA.
¹⁹ Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
²⁰ Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, Szczecin, Poland.
²¹ Department of Clinical Genetics, Birmingham Women's Hospital, Birmingham, UK.
²² Hereditary Cancer Program, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, Barcelona, Spain.
²³ University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
²⁴ Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.
²⁵ Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, UK.
²⁶ Royal Hallamshire Hospital, Sheffield, UK.
²⁷ Basser Research Center, University of Pennsylvania, Philadelphia, PA, USA.
²⁸ Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
²⁹ Center for Familial Breast and Ovarian Cancer and Center for Integrated Oncology (CIO), Faculty of Medicine, University Hospital Cologne, Cologne, Germany.
³⁰ Clinical Genetics Service, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
³¹ Department of Laboratory Genetics and IPO Porto Research Center, Portuguese Oncology Institute (IPO Porto), Porto, Portugal; School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal.
³² Department of Laboratory Genetics and IPO Porto Research Center, Portuguese Oncology Institute (IPO Porto), Porto, Portugal.
³³ Cancer Research Program, Research Institute of McGill University Health Centre, Montreal, Canada; Lady Davis Institute and Division of Medical Genetics, Jewish General Hospital, McGill University, Montreal, Canada.
³⁴ Cancer Research Program, Research Institute of McGill University Health Centre, Montreal, Canada; Departments of Surgery and Oncology, McGill University, Montreal, Canada.
³⁵ West of Scotland Genetic Service, Queen Elizabeth University Hospital, Glasgow, UK.
³⁶ Department of Clinical Genetics, Netherlands Cancer Institute, Amsterdam, The Netherlands.
³⁷ Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.
³⁸ Department of Human Genetics, Amsterdam University Medical Center, Amsterdam, The Netherlands.
³⁹ School of Clinical Medicine, UNSW Medicine & Health, University of New South Wales, Sydney, Australia; Hereditary Cancer Centre, Prince of Wales Hospital, Randwick, Australia.
⁴⁰ Prince of Wales Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia; Hereditary Cancer Centre, Prince of Wales Hospital, Randwick, Australia.
⁴¹ The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia.
⁴² Department of General Practice and Primary Care, University of Melbourne, Melbourne, Australia.
⁴³ Oxford Centre for Genomic Medicine, Oxford University Hospitals NHS Trust, Oxford, UK.
⁴⁴ Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
⁴⁵ Northern Genetics Service, Newcastle upon Tyne Hospitals, Newcastle upon Tyne, UK.
⁴⁶ St. George's Hospital, London, UK.
⁴⁷ Familial Cancer Centre, Monash Health, Clayton, Australia.
⁴⁸ East Anglian Medical Genetics Service, Cambridge University Hospitals NHS Trust, Cambridge, UK; Department of Genomic Medicine, NIHR Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK.
⁴⁹ East Anglian Medical Genetics Service, Cambridge University Hospitals NHS Trust, Cambridge, UK.
⁵⁰ Familial Cancer Service, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, Australia; Centre for Cancer Research, Westmead Institute for Medical Research, Sydney Medical School, University of Sydney, Sydney, Australia.
⁵¹ Genetic Health Queensland, Royal Brisbane & Women's Hospital, Herston, Australia.
⁵² The Adelson School of Medicine and Department of Molecular Biology, Ariel University, Ariel, Israel; The Genetic Institute, Kaplan Medical Center, Rehovot, Israel.
⁵³ Hunter Family Cancer Service, Waratah, Australia; St. Vincent's Clinical School, University of New South Wales, Sydney, Australia; Cancer Genetics Clinic, The Kinghorn Cancer Centre, St. Vincent's Hospital, Sydney, Australia.
⁵⁴ Genetic Services of Western Australia, King Edward Memorial Hospital, Subiaco, Australia; Faculty of Health and Medical Sciences, University of Western Australia, Perth, Australia.
⁵⁵ North East Thames Regional Genetics Service, Great Ormond Street Hospital NHS Foundation Trust, London, UK.
⁵⁶ Hospital de Sant Pau, Barcelona, Spain.
⁵⁷ Institute of Oncology, Ljubljana, Slovenia.
⁵⁸ Department of Clinical Genetics, Royal Devon and Exeter Hospital, Exeter, UK.
⁵⁹ Hereditary Cancer Genetics Group, Medical Oncology Department, Hospital Vall d'Hebron, Vall d'Hebron Institute of Oncology, Barcelona, Spain; Medical Oncology Department, Hospital Clínico Univesitario Lozano Blesa, Zaragoza, Spain.
⁶⁰ Hereditary Cancer Genetics Group, Medical Oncology Department, Hospital Vall d'Hebron, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
⁶¹ North West Thames Regional Genetics Service, Northwick Park Hospital, London North West University Healthcare NHS Trust, Harrow, UK.
⁶² St. James's Hospital, Dublin, Ireland.
⁶³ St. Michael's Hospital, Bristol, UK.
⁶⁴ University of Leicester, Leicester, UK; University Hospitals Leicester, Leicester, UK.
⁶⁵ Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
⁶⁶ Chaim Sheba Medical Center, Tel-Hashomer, Israel.
⁶⁷ Fox Chase Cancer Center, Philadelphia, PA, USA.
⁶⁸ Clinical Genetics Service, Liverpool Women's Hospital, Liverpool, UK.
⁶⁹ Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India.
⁷⁰ National Cancer Institute, Bratislava, Slovakia.
⁷¹ North Bristol NHS Trust, Bristol, UK; University of Exeter Medical School, Exeter, UK.
⁷² New Cross Hospital, Wolverhampton, UK.
⁷³ MD Anderson Cancer Center, University of Texas, Houston, TX, USA.
⁷⁴ Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
⁷⁵ Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁷⁶ Hospital Universitario 12 de Octubre, Madrid, Spain.
⁷⁷ Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK.
⁷⁸ Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK; Cancer Sciences, The University of Southampton, Southampton, UK.
⁷⁹ Imperial College Healthcare NHS Trust, London, UK.
⁸⁰ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁸¹ Churchill Hospital, Oxford, UK; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
⁸² Cancer Genetics Unit and Academic Urology Unit, The Royal Marsden NHS Foundation Trust, London, UK; St. George's Hospital, London, UK; Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK; Department of Medicine, The University of Melbourne, Parkville, Australia.
⁸³ Department of Translational Medicine, Lund University, Malmö, Sweden; Departments of Pathology and Laboratory Medicine, Surgery and Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
⁸⁴ Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia; Department of Medicine, The University of Melbourne, Parkville, Australia; Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
⁸⁵ Department of Urology, Akershus University Hospital, Lørenskog, Norway.
⁸⁶ Royal Surrey Hospital, Guildford, UK.
⁸⁷ University College London Hospitals NHS Foundation Trust, London, UK.
⁸⁸ Centre for Cancer Screening, Prevention and Early Diagnosis, Wolfson Institute of Population Health, Queen Mary University, London, UK.
⁸⁹ Technion-Israel Institute of Technology, Haifa, Israel.
⁹⁰ Nottingham City Hospital, Nottingham, UK.
⁹¹ University Hospital Southampton, Southampton, UK.
⁹² Oncogenetics Team, Genetics and Epidemiology, The Institute of Cancer Research, London, UK; Cancer Genetics Unit and Academic Urology Unit, The Royal Marsden NHS Foundation Trust, London, UK. Electronic address: ros.eeles@icr.ac.uk.

PMID: 41714267
DOI: 10.1016/j.eururo.2026.01.031

Free article

Targeted Prostate Cancer Screening in Carriers of BRCA1 or BRCA2 Pathogenic Germline Variants Detects Clinically Relevant Disease: 5-year Results from the IMPACT Study

Elizabeth K Bancroft et al. Eur Urol. 2026.

Free article

. 2026 Feb 18:S0302-2838(26)00057-6.

doi: 10.1016/j.eururo.2026.01.031. Online ahead of print.

Authors

Affiliations

¹ Oncogenetics Team, Genetics and Epidemiology, The Institute of Cancer Research, London, UK; Cancer Genetics Unit and Academic Urology Unit, The Royal Marsden NHS Foundation Trust, London, UK.
² Oncogenetics Team, Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
³ Cancer Genetics Unit and Academic Urology Unit, The Royal Marsden NHS Foundation Trust, London, UK.
⁴ Department of Genomic Medicine, Division of Evolution, Infection and Genomic Sciences, University of Manchester, Manchester, UK.
⁵ Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
⁶ Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
⁷ Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Department of Genetic Medicine, Royal Melbourne Hospital, Parkville, Australia.
⁸ Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia.
⁹ Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK.
¹⁰ Dutch Foundation for Detection of Hereditary Tumors, Leiden, The Netherlands; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
¹¹ Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
¹² Radboud University Medical Center, Nijmegen, The Netherlands.
¹³ Dutch Foundation for Detection of Hereditary Tumors, Leiden, The Netherlands.
¹⁴ Department of Genetics, Division Laboratories, Pharmacy and Biomedical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands.
¹⁵ Department of Clinical Genetics, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark.
¹⁶ Department of Urology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark.
¹⁷ John and Carol Walter Center for Urological Health, Division of Urology, Endeavor Health NorthShore University HealthSystem, Evanston, IL, USA.
¹⁸ Internal Medicine Epidemiology, Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, IL, USA.
¹⁹ Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
²⁰ Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, Szczecin, Poland.
²¹ Department of Clinical Genetics, Birmingham Women's Hospital, Birmingham, UK.
²² Hereditary Cancer Program, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, Barcelona, Spain.
²³ University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
²⁴ Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.
²⁵ Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, UK.
²⁶ Royal Hallamshire Hospital, Sheffield, UK.
²⁷ Basser Research Center, University of Pennsylvania, Philadelphia, PA, USA.
²⁸ Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
²⁹ Center for Familial Breast and Ovarian Cancer and Center for Integrated Oncology (CIO), Faculty of Medicine, University Hospital Cologne, Cologne, Germany.
³⁰ Clinical Genetics Service, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
³¹ Department of Laboratory Genetics and IPO Porto Research Center, Portuguese Oncology Institute (IPO Porto), Porto, Portugal; School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal.
³² Department of Laboratory Genetics and IPO Porto Research Center, Portuguese Oncology Institute (IPO Porto), Porto, Portugal.
³³ Cancer Research Program, Research Institute of McGill University Health Centre, Montreal, Canada; Lady Davis Institute and Division of Medical Genetics, Jewish General Hospital, McGill University, Montreal, Canada.
³⁴ Cancer Research Program, Research Institute of McGill University Health Centre, Montreal, Canada; Departments of Surgery and Oncology, McGill University, Montreal, Canada.
³⁵ West of Scotland Genetic Service, Queen Elizabeth University Hospital, Glasgow, UK.
³⁶ Department of Clinical Genetics, Netherlands Cancer Institute, Amsterdam, The Netherlands.
³⁷ Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.
³⁸ Department of Human Genetics, Amsterdam University Medical Center, Amsterdam, The Netherlands.
³⁹ School of Clinical Medicine, UNSW Medicine & Health, University of New South Wales, Sydney, Australia; Hereditary Cancer Centre, Prince of Wales Hospital, Randwick, Australia.
⁴⁰ Prince of Wales Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia; Hereditary Cancer Centre, Prince of Wales Hospital, Randwick, Australia.
⁴¹ The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia.
⁴² Department of General Practice and Primary Care, University of Melbourne, Melbourne, Australia.
⁴³ Oxford Centre for Genomic Medicine, Oxford University Hospitals NHS Trust, Oxford, UK.
⁴⁴ Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
⁴⁵ Northern Genetics Service, Newcastle upon Tyne Hospitals, Newcastle upon Tyne, UK.
⁴⁶ St. George's Hospital, London, UK.
⁴⁷ Familial Cancer Centre, Monash Health, Clayton, Australia.
⁴⁸ East Anglian Medical Genetics Service, Cambridge University Hospitals NHS Trust, Cambridge, UK; Department of Genomic Medicine, NIHR Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK.
⁴⁹ East Anglian Medical Genetics Service, Cambridge University Hospitals NHS Trust, Cambridge, UK.
⁵⁰ Familial Cancer Service, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, Australia; Centre for Cancer Research, Westmead Institute for Medical Research, Sydney Medical School, University of Sydney, Sydney, Australia.
⁵¹ Genetic Health Queensland, Royal Brisbane & Women's Hospital, Herston, Australia.
⁵² The Adelson School of Medicine and Department of Molecular Biology, Ariel University, Ariel, Israel; The Genetic Institute, Kaplan Medical Center, Rehovot, Israel.
⁵³ Hunter Family Cancer Service, Waratah, Australia; St. Vincent's Clinical School, University of New South Wales, Sydney, Australia; Cancer Genetics Clinic, The Kinghorn Cancer Centre, St. Vincent's Hospital, Sydney, Australia.
⁵⁴ Genetic Services of Western Australia, King Edward Memorial Hospital, Subiaco, Australia; Faculty of Health and Medical Sciences, University of Western Australia, Perth, Australia.
⁵⁵ North East Thames Regional Genetics Service, Great Ormond Street Hospital NHS Foundation Trust, London, UK.
⁵⁶ Hospital de Sant Pau, Barcelona, Spain.
⁵⁷ Institute of Oncology, Ljubljana, Slovenia.
⁵⁸ Department of Clinical Genetics, Royal Devon and Exeter Hospital, Exeter, UK.
⁵⁹ Hereditary Cancer Genetics Group, Medical Oncology Department, Hospital Vall d'Hebron, Vall d'Hebron Institute of Oncology, Barcelona, Spain; Medical Oncology Department, Hospital Clínico Univesitario Lozano Blesa, Zaragoza, Spain.
⁶⁰ Hereditary Cancer Genetics Group, Medical Oncology Department, Hospital Vall d'Hebron, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
⁶¹ North West Thames Regional Genetics Service, Northwick Park Hospital, London North West University Healthcare NHS Trust, Harrow, UK.
⁶² St. James's Hospital, Dublin, Ireland.
⁶³ St. Michael's Hospital, Bristol, UK.
⁶⁴ University of Leicester, Leicester, UK; University Hospitals Leicester, Leicester, UK.
⁶⁵ Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
⁶⁶ Chaim Sheba Medical Center, Tel-Hashomer, Israel.
⁶⁷ Fox Chase Cancer Center, Philadelphia, PA, USA.
⁶⁸ Clinical Genetics Service, Liverpool Women's Hospital, Liverpool, UK.
⁶⁹ Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India.
⁷⁰ National Cancer Institute, Bratislava, Slovakia.
⁷¹ North Bristol NHS Trust, Bristol, UK; University of Exeter Medical School, Exeter, UK.
⁷² New Cross Hospital, Wolverhampton, UK.
⁷³ MD Anderson Cancer Center, University of Texas, Houston, TX, USA.
⁷⁴ Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
⁷⁵ Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁷⁶ Hospital Universitario 12 de Octubre, Madrid, Spain.
⁷⁷ Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK.
⁷⁸ Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK; Cancer Sciences, The University of Southampton, Southampton, UK.
⁷⁹ Imperial College Healthcare NHS Trust, London, UK.
⁸⁰ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁸¹ Churchill Hospital, Oxford, UK; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
⁸² Cancer Genetics Unit and Academic Urology Unit, The Royal Marsden NHS Foundation Trust, London, UK; St. George's Hospital, London, UK; Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK; Department of Medicine, The University of Melbourne, Parkville, Australia.
⁸³ Department of Translational Medicine, Lund University, Malmö, Sweden; Departments of Pathology and Laboratory Medicine, Surgery and Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
⁸⁴ Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia; Department of Medicine, The University of Melbourne, Parkville, Australia; Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
⁸⁵ Department of Urology, Akershus University Hospital, Lørenskog, Norway.
⁸⁶ Royal Surrey Hospital, Guildford, UK.
⁸⁷ University College London Hospitals NHS Foundation Trust, London, UK.
⁸⁸ Centre for Cancer Screening, Prevention and Early Diagnosis, Wolfson Institute of Population Health, Queen Mary University, London, UK.
⁸⁹ Technion-Israel Institute of Technology, Haifa, Israel.
⁹⁰ Nottingham City Hospital, Nottingham, UK.
⁹¹ University Hospital Southampton, Southampton, UK.
⁹² Oncogenetics Team, Genetics and Epidemiology, The Institute of Cancer Research, London, UK; Cancer Genetics Unit and Academic Urology Unit, The Royal Marsden NHS Foundation Trust, London, UK. Electronic address: ros.eeles@icr.ac.uk.

PMID: 41714267
DOI: 10.1016/j.eururo.2026.01.031

Abstract

Background and objective: BRCA1 and BRCA2 pathogenic germline variants (PGVs) are associated with higher risk of prostate cancer (PC). The IMPACT study evaluated the utility of targeted prostate-specific antigen (PSA) screening in BRCA1/BRCA2 PGV carriers. Here we report outcomes after five rounds of PSA screening in IMPACT.

Methods: Between 2005 and 2015, 3063 participants aged 40-69 yr (median 54 yr) were recruited from 65 centres in 20 countries in two cohorts: (1) BRCA1/BRCA2 PGV carriers (915 BRCA1, 901 BRCA2); and (2) age-matched noncarriers for a familial PGV (727 BRCA1 and 520 BRCA2 noncarriers). Annual PSA screening was performed, with PSA >3.0 ng/ml used as the indication for prostate biopsy. Our aim was to identify differences by PGV status in (1) the incidence of PC and of clinically significant PC (csPC; grade group ≥2) and (2) tumour stage and characteristics after five screening rounds.

Key findings and limitations: There was no statistically significant difference in PC incidence between BRCA1/BRCA2 PGV carriers and noncarriers. csPC incidence was significantly higher for BRCA2 PGV carriers than for noncarriers (3.1% vs 1.3%; p = 0.04). Among men with PC, the proportion of tumours with National Comprehensive Cancer Network intermediate unfavourable/high risk was higher in the BRCA1/BRCA2 PGV groups versus the corresponding group without PGVs (BRCA2: 65% vs 32%, p = 0.029; BRCA1: 56% vs 18%, p = 0.0017). There were no T4 or metastatic PC cases. Pathology after radical prostatectomy revealed tumour upgrading for 7/23 (26%) BRCA1 PGV carriers and 10/34 (26%) BRCA2 PGV carriers, with no tumour upgrading for men without PGVs. Study limitations include the biopsy compliance rate and changes in PC diagnostic pathways since 2005.

Conclusions and clinical implications: Annual PSA screening in BRCA2 PGV carriers confirmed a higher incidence of csPC and detection of clinically relevant tumours in comparison to noncarriers. For the first time, we confirm that PSA screening in BRCA1 PGV carriers results in early detection of NCCN IR-U/HR PC. Systematic PSA screening is recommended for BRCA2 PGV carriers and should be considered for BRCA1 PGV carriers.

Keywords: BRCA1; BRCA2; Cancer screening; Prostate cancer; Prostate-specific antigen.

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Targeted Prostate Cancer Screening in Carriers of BRCA1 or BRCA2 Pathogenic Germline Variants Detects Clinically Relevant Disease: 5-year Results from the IMPACT Study

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Targeted Prostate Cancer Screening in Carriers of BRCA1 or BRCA2 Pathogenic Germline Variants Detects Clinically Relevant Disease: 5-year Results from the IMPACT Study

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Abstract

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