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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

Bancroft, Elizabeth K ; Page, Elizabeth C ; McHugh, Jana ; Thomas, Sarah ; Taylor, Natalie ; Pope, Jennifer ; Evans, D Gareth ; Rothwell, Jeanette ; Grindedal, Eli Marie and Maehle, Lovise , et al. (2026) In European Urology 89(5). p.457-468
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... (More)

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.

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keywords
Humans, Male, Prostatic Neoplasms/genetics, Middle Aged, Aged, Germ-Line Mutation, Adult, Early Detection of Cancer/methods, Prostate-Specific Antigen/blood, BRCA2 Protein/genetics, Genetic Predisposition to Disease, BRCA1 Protein/genetics, Incidence, Heterozygote, Kallikreins/blood, Neoplasm Staging, Genes, BRCA2
in
European Urology
volume
89
issue
5
pages
457 - 468
publisher
Elsevier
external identifiers
  • pmid:41714267
  • scopus:105030464445
ISSN
0302-2838
DOI
10.1016/j.eururo.2026.01.031
language
English
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yes
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Copyright © 2026 The Author(s). Published by Elsevier B.V. All rights reserved.
id
b3d61180-403a-4983-965c-6ce595ca1930
date added to LUP
2026-05-10 14:09:56
date last changed
2026-05-12 02:42:44
@article{b3d61180-403a-4983-965c-6ce595ca1930,
  abstract     = {{<p>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.</p><p>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 &gt;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.</p><p>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.</p><p>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.</p>}},
  author       = {{Bancroft, Elizabeth K and Page, Elizabeth C and McHugh, Jana and Thomas, Sarah and Taylor, Natalie and Pope, Jennifer and Evans, D Gareth and Rothwell, Jeanette and Grindedal, Eli Marie and Maehle, Lovise and James, Paul and McKinley, Joanne and Mascarenhas, Lyon and Side, Lucy and Thomas, Tessy and van Leerdam, Monique E and van Asperen, Christi J and Kiemeney, Lambertus A L M and Ringelberg, Janneke and Vlaming, Michiel and Rønlund, Karina and Osther, Palle J S and Helfand, Brian T and Hutten, Christina G and Oldenburg, Rogier A and Cybulski, Cezary and Wokolorczyk, Dominika and Ong, Kai-Ren and Huber, Camilla and Salinas, Monica and Feliubadaló, Lidia and Oosterwijk, Jan C and van Zelst-Stams, Wendy A G and Cook, Jackie and Rosario, Derek J and Maxwell, Kara and Powers, Jacquelyn and Buys, Saundra and Lyman, Jo and Ausems, Margreet G E M and Schmutzler, Rita K and Rhiem, Kerstin and Izatt, Louise and Tripathi, Vishakha and Teixeira, Manuel R and Cardoso, Marta and Foulkes, William D and Hall, Michael J and Lilja, Hans}},
  issn         = {{0302-2838}},
  keywords     = {{Humans; Male; Prostatic Neoplasms/genetics; Middle Aged; Aged; Germ-Line Mutation; Adult; Early Detection of Cancer/methods; Prostate-Specific Antigen/blood; BRCA2 Protein/genetics; Genetic Predisposition to Disease; BRCA1 Protein/genetics; Incidence; Heterozygote; Kallikreins/blood; Neoplasm Staging; Genes, BRCA2}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{457--468}},
  publisher    = {{Elsevier}},
  series       = {{European Urology}},
  title        = {{Targeted Prostate Cancer Screening in Carriers of BRCA1 or BRCA2 Pathogenic Germline Variants Detects Clinically Relevant Disease : 5-year Results from the IMPACT Study}},
  url          = {{http://dx.doi.org/10.1016/j.eururo.2026.01.031}},
  doi          = {{10.1016/j.eururo.2026.01.031}},
  volume       = {{89}},
  year         = {{2026}},
}