Targeted Prostate Cancer Screening in Carriers of BRCA1 or BRCA2 Pathogenic Germline Variants Detects Clinically Relevant Disease: 5-year Results from the IMPACT Study.
Level 3 - non-randomized controlled study
Prospective multicenter non-randomized controlled cohort study with matched controls
PubMed 41714267 · doi:10.1016/j.eururo.2026.01.031
What was done
The prospective multicenter IMPACT study evaluated 5 rounds of annual prostate-specific antigen (PSA) screening among 3,063 men aged 40–69 years (median 54 years) across 65 centres in 20 countries. Participants included pathogenic germline variant (PGV) carriers (915 BRCA1, 901 BRCA2) and age-matched familial noncarrier controls (727 BRCA1 noncarriers, 520 BRCA2 noncarriers). A PSA level >3.0 ng/ml served as the indication for prostate biopsy. Primary outcomes were overall prostate cancer (PC) incidence, clinically significant PC (csPC; grade group ≥2) incidence, and tumour risk characteristics across groups.
What was found
Overall PC incidence did not differ significantly between carriers and noncarriers. csPC incidence was significantly higher in BRCA2 PGV carriers than noncarriers (3.1% vs 1.3%; p = 0.04). Among men diagnosed with PC, intermediate unfavourable or high-risk disease by NCCN criteria was more common in PGV carriers than noncarriers for both BRCA2 (65% vs 32%; p = 0.029) and BRCA1 (56% vs 18%; p = 0.0017). No T4 or metastatic cases were detected. Radical prostatectomy pathology showed upgrading in 26% of BRCA1 carriers (7/23) and 26% of BRCA2 carriers (10/34), compared to 0% in noncarriers.
Why it matters
These 5-year results support systematic PSA screening for BRCA2 mutation carriers and demonstrate that targeted screening in BRCA1 carriers identifies higher-risk disease at an early, non-metastatic stage.
Limits
The study is an observational cohort rather than a randomized trial. Diagnostic pathways reflect protocols established in 2005 (relying on PSA thresholds without upfront multiparametric MRI), biopsy compliance was incomplete, and cancer-specific mortality was not reported.
Cited by
- supports Men carrying BRCA gene mutations have a higher risk of prostate cancer and other forms of cancer.