Bancroft, Elizabeth K., Page, Elizabeth C. and McHugh, Jana , (2026) Targeted prostate cancer screening in BRCA1 or BRCA2 pathogenic germline variant carriers detects clinically relevant disease- Five-year results of the IMPACT study. European Urology. (doi:10.1016/j.eururo.2026.01.031).
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Article
Abstract
Background and Objective: BRCA1 or BRCA2 pathogenic germline variants(PGV) increase the risk of prostate cancer (PrCa). The IMPACT study evaluates utility of targeted prostate-specific antigen (PSA) screening in BRCA1/BRCA2 carriers. We report the outcomes from five rounds of PSA-screening.
Methods:
3,063 participants aged 40–69 (median age 54yrs) were recruited between 2005-2015 from 65 centres in 20 countries in two cohorts:
i)BRCA1/BRCA2 PGV carriers (915BRCA1/901BRCA2 carriers)
ii)age-matched non-carriers for a familial PGV, (727BRCA1/520BRCA2 non- carriers).
Annual PSA-screening was performed; a PSA>3.0ng/mL indicating prostate biopsy (PB). After 5 screening rounds we aimed to identify a difference in (i) PrCa and Clinically Significant (CS,(≥Grade Group 2(GG)) PrCa incidence, (ii) tumour stage and characteristics, by PGV status.
Key Findings and Limitations:
No statistically significant difference observed in PrCa incidence between BRCA1/BRCA2 PGV carriers and non-carriers. Incidence of CS-PrCa was significantly higher in BRCA2 carriers than non-carriers (3.1%vs1.3%,p=0.04). BRCA1/BRCA2 carriers had a higher proportion of NCCN intermediate- unfavourable/high-risk disease compared with non-carriers (BRCA2: 65%vs32%;p=0.031, BRCA1: 56%vs18%;p=0.0015). There were no T4 or metastatic cases. Post-surgery, 7/23(26%)BRCA1 and 10/34(26%)BRCA2 carriers
11 of 33 had a tumour GG increase; zero non-carriers tumour-GG increased. Limitations of 246 the study were biopsy compliance and PrCa diagnostic pathway changes since 2005.
Conclusion and Clinical Implications: Annual PSA-screening in BRCA2 carriers 250 confirms a higher incidence of CS-PrCa and detection of clinically relevant tumours 251 compared with non-carriers. For the first time we confirm PSA-screening results in the early detection of NCCN intermediate-unfavourable/high-risk PrCa in BRCA1 carriers. Therefore, systematic PSA-screening in BRCA2 carriers is recommended 254 and should be considered for BRCA1 carriers.
Patient Summary
In this study we offered prostate cancer screening to carriers and non-carriers of pathogenic variants in the BRCA1 and BRCA2 genes. We found that screening identifies clinically relevant disease and that PSA screening should be recommended for all BRCA1 and BRCA2 carriers.
Text
Targeted prostate cancer screening in BRCA1 or BRCA2 pathogenic 1 germline variant carriers detects clinically relevant disease- Five-year 2 results of the IMPACT study
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More information
Accepted/In Press date: 29 January 2026
e-pub ahead of print date: 18 February 2026
Identifiers
Local EPrints ID: 510102
URI: http://eprints.soton.ac.uk/id/eprint/510102
ISSN: 0302-2838
PURE UUID: a569d83c-48aa-401a-af09-8f15330ebd3e
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Date deposited: 17 Mar 2026 18:02
Last modified: 18 Mar 2026 02:33
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Contributors
Author:
Elizabeth K. Bancroft
Author:
Elizabeth C. Page
Author:
Jana McHugh
Corporate Author: et al.
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