| 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. |
| Authors: |
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, K-R; 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 |
| Contributors: |
Dearnaley, David; Brook, Mark; Kote-Jarai, Zsofia; Eeles, Rosalind |
| Publisher Information: |
Elsevier BV |
| Publication Year: |
2026 |
| Collection: |
The Institute of Cancer Research (ICR): Publications Repository |
| Subject Terms: |
BRCA1; BRCA2; Cancer screening; Prostate cancer; Prostate-specific antigen |
| Subject Geographic: |
Switzerland |
| Description: |
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 ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
Print-Electronic; S0302-2838(26)00057-6 -; application/pdf |
| Language: |
English |
| ISSN: |
1873-7560; 0302-2838 |
| Relation: |
S0302-2838(26)00057-6; European Urology, 2026, pp. S0302-2838(26)00057-6 -; https://repository.icr.ac.uk/handle/internal/7542 |
| DOI: |
10.1016/j.eururo.2026.01.031 |
| Availability: |
https://doi.org/10.1016/j.eururo.2026.01.031; https://repository.icr.ac.uk/handle/internal/7542 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.596679F8 |
| Database: |
BASE |