Final results from the IMPACT study support screening measures, but open questions remain
The final analysis of the IMPACT study provides strong evidence that targeted prostate-specific antigen (PSA) screening identifies clinically meaningful prostate cancer in men at high genetic risk for this tumour type, and supports systematic annual PSA screening for BRCA2 carriers and structured screening for BRCA1 carriers (Eur Urol. 2026 May;89(5):457-468).
The study recruited over 3,000 participants across 65 centers in 20 countries between 2005 and 2015, including 1,816 BRCA1/2 carriers and 1,247 noncarriers aged 40-60 years. All participants underwent five annual PSA tests, with a biopsy recommended for PSA >3.0 ng/mL. The final analysis reported on outcomes after completion of the planned five screening rounds, the primary endpoint of the study.
Across the cohort, 20% of participants reached the biopsy threshold at least once, and 126 prostate cancers were diagnosed. The authors note that “annual PSA screening in BRCA2 PGV carriers confirmed a higher incidence of clinically significant prostate cancer,” with clinically significant prostate cancer detected in 3.1% of BRCA2 carriers versus 1.3% of noncarriers. BRCA2 carriers were diagnosed at a younger median age and exhibited a markedly higher proportion of NCCN unfavorable-intermediate-risk or high‑risk tumors (65% vs 32%, respectively). These findings reinforce the association with BRCA2 and more aggressive prostate cancer features.
While overall cancer incidence among BRCA1 carriers did not differ significantly from noncarriers, the pattern of prostate cancers detected was notably more adverse. Study findings show that PSA screening “results in early detection of NCCN intermediate/high risk prostate cancer” in BRCA1 carriers, with over half (56%) of screen‑detected tumors falling into higher‑risk categories compared with 18% in noncarriers. No metastatic or T4 cancers were observed in any group, highlighting the potential of structured early detection.
While the pioneering efforts of the IMPACT study stand as an impressive example of international collaboration in genetic cancer prevention, key open questions remain, such as how to build on these findings and further refine tailored screening programmes for prostate cancer risk. For instance, can we do better than using a PSA cut-point of 3.0ng/mL? What is the best way to incorporate magnetic resonance imaging (MRI) into screening, particularly with global variance in availability of MRI? And, how to best take into consideration the emergence of polygenic risk scores alongside rare genetic variants? The role of germline genetic testing for prostate cancer risk has been established in large part through this study, and findings should now inspire the field to continue its momentum of progress and collaboration.
