European Urology has published the first year's screening results of the IMPACT study—a trial set up to evaluate targeted prostate cancer screening in men with BRCA1/BRCA2 mutations, who have a 1.8–8.6-fold increased risk of developing this cancer.

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2,481 men aged 40–69 years (791 BRCA1 carriers, 531 BRCA1 controls, 731 BRCA2 carriers, and 428 BRCA2 controls) from 62 centres in 20 countries were enrolled in the study. In total, 199 men (8%) presented with PSA levels of >3.0 ng/ml, 162 biopsies were performed, and 59 prostate cancers were diagnosed—18 in BRCA1 carriers (2.3%), 10 in BRCA1 controls (1.9%), 24 in BRCA2 carriers (3.3%), and seven in BRCA2 controls (1.6%).

Although differences between the detection rates for carriers and controls were not deemed to be statistically significant, they suggest a trend towards improved detection in men with BRCA1/BRCA2 mutations, and the authors predict that these differences will increase over the next few years of follow-up assessment. “We will continue to follow up this cohort for a further 5 years and expect to offer clinical recommendations for the management of men with BRCA1/2 mutations,” says Rosalind Eeles, who led the study.

A similar trend was observed in the positive predictive value (PPV) of biopsy using a PSA threshold of 3.0 ng/ml, which was 48% versus 33.3% in BRCA2 carriers and controls, respectively, and 37.5% versus 23.3% in BRCA1 carriers and controls, respectively. Again, differences were not statistically significant, but the authors note that a PPV of 48% is about twofold greater than the PPVs reported in population-screening studies such as the ERSPC, possibly owing to the fact that the IMPACT study involved younger men.

BRCA2 carriers are thought to present at a younger age with more aggressive disease, and Bancroft et al. reported a significant difference in the rates of intermediate-risk and high-risk disease between BRCA2 carriers and controls (71% versus 43%). Conversely, men with the BRCA1 mutation were less likely to be diagnosed with intermediate-risk or high-risk disease than controls (61% versus 80%), highlighting the complexity of the situation. Although some data suggest that BRCA1 carriers are more likely to present with aggressive disease, an association is far from clear.

The authors suggest lowering the PSA threshold in BRCA2 carriers to increase the detection of early-stage cancers, although they stress that the results of their study cannot be generalized to all ethnic groups, as 95% of the men were white. “Future research will be directed at using targeted screening for other genetically high-risk cohorts; for example, we have recently started to recruit men with mismatch repair gene mutations following reports that prostate cancer incidence is higher in these men,” explains Eeles.