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 Maehle, Lovise
Bancroft, Elizabeth K
Page, Elizabeth C
McHugh, Jana
Thomas, Sarah
Taylor, Natalie
Pope, Jennifer
Evans, D Gareth
Rothwell, Jeanette
Grindedal, Eli Marie
Maehle, Lovise
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.
MIDER Authors
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Date
2026-02-18
Type
Article
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Citation
Bancroft EK, Page EC, McHugh J, Thomas S, Taylor N, Pope J, Evans DG, Rothwell J, Grindedal EM, Maehle L, James P, McKinley J, Mascarenhas L, Side L, Thomas T, van Leerdam ME, van Asperen CJ, Kiemeney LALM, Ringelberg J, Vlaming M, Rønlund K, Osther PJS, Helfand BT, Hutten CG, Oldenburg RA, Cybulski C, Wokolorczyk D, Ong KR, Huber C, Salinas M, Feliubadaló L, Oosterwijk JC, van Zelst-Stams WAG, Cook J, Rosario DJ, Maxwell K, Powers J, Buys S, Lyman J, Ausems MGEM, Schmutzler RK, Rhiem K, Izatt L, Tripathi V, Teixeira MR, Cardoso M, Foulkes WD, Aprikian A, Davidson R, Longmuir M, Ruijs MWG, Blom EW, van Engelen K, Williams R, Andrews L, Murphy DG, Saya S, Halliday D, Walker L, Liljegren A, Carlsson S, Azzabi A, Jobson I, Snape K, Gowie M, Harris M, Tischkowitz M, Taylor A, Kirk J, Susman R, Chen-Shtoyerman R, Spigelman A, Pachter N, Ahmed M, Cajal TRY, Krajc M, Cleaver R, Cruellas M, Perez-Ballestero E, Brady AF, Gallagher D, Donaldson A, Barwell J, Nicolai N, Friedman E, Hall MJ, Greenhalgh L, Murthy V, Copakova L, McGrath JS, Cooke P, Arun B, Myhill K, Hogben M, Hussain S, Aaronson NK, Ardern-Jones A, Bangma CH, Castro E, Dearnaley D, Eccles DM, Tricker K, Falconer A, Gronberg H, Hamdy FC, Khoo V, Lilja H, Lindeman GJ, Lubinski J, Axcrona K, Mikropoulos C, Mitra A, Offman J, Rennert G, Suri M, Dudderidge T; IMPACT Study Collaborators; Brook MN, Kote-Jarai Z, Eeles RA. Targeted Prostate Cancer Screening in Carriers of BRCA1 or BRCA2 Pathogenic Germline Variants Detects Clinically Relevant Disease: 5-year Results from the IMPACT Study. Eur Urol. 2026 May;89(5):457-468. doi: 10.1016/j.eururo.2026.01.031. Epub 2026 Feb 18.