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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Le résumé fourni par la source
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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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Targeted Prostate Cancer Screening in Carriers of BRCA1 or BRCA2 Pathogenic Germline Variants Detects Clinically Relevant Disease: 5-year Results from the IMPACT Study
- Date Crossref
- 01/05/2026
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Cancer Research UK pays non établi dans la noticeOrganisation à but non lucratif
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Institute of Cancer Research Genetics and Epidemiology pays non établi dans la noticeStructure de recherche
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Royal Marsden NHS Foundation Trust Cancer Genetics Unit and Academic Urology Unit pays non établi dans la noticeÉtablissement de santé
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University of Manchester Department of Genomic Medicine pays non établi dans la noticeUniversité ou école supérieure
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Manchester Academic Health Science Centre pays non établi dans la noticeÉtablissement de santé
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Oslo University Hospital Department of Medical Genetics pays non établi dans la noticeÉtablissement de santé
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Peter MacCallum Cancer Centre Parkville Familial Cancer Centre pays non établi dans la noticeÉtablissement de santé
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The Royal Melbourne Hospital pays non établi dans la noticeOrganisme public
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Princess Anne Hospital pays non établi dans la noticeÉtablissement de santé
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Leiden University Medical Center Department of Gastroenterology and Hepatology pays non établi dans la noticeOrganisme public
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Radboud University Nijmegen pays non établi dans la noticeUniversité ou école supérieure
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Radboud University Medical Center Department of Human Genetics pays non établi dans la noticeOrganisme public
Cancer Research UK, Genetics and Epidemiology — Institute of Cancer Research et Cancer Genetics Unit and Academic Urology Unit — Royal Marsden NHS Foundation Trust, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.