Identification of men with a genetic predisposition to prostate cancer: Targeted screening in men at higher genetic risk and controls—The IMPACT study.

12 Background: IMPACT is a multi-national targeted prostate cancer screening study of men with a known germline mutation which is thought to predispose to the disease. The study is recruiting male BRCA1/2 mutation carriers and a control group, who have tested negative for a mutation present in their family, from 52 centres in 17 countries. Methods: Eligible men aged 40-69 years are offered annual serum PSA testing for at least five years. The PSA threshold used to determine prostate biopsy is >3ng/ml. All men are offered a biopsy irrespective of PSA level after 5 years of screening. Men are also invited to take part in a Quality of Life sub-study. Results: To date 1819/ 1850 men have been recruited (593 BRCA1, 580 BRCA2, 638 Controls). 213 presented with a PSA ≥3ng/ml and 159 biopsies have been performed (54 men have either declined the biopsy or are awaiting results) and 60 men have been diagnosed with prostate cancer (31 BRCA2 carriers, 16 BRCA1 carriers and 13 controls). 45% of cases diagnosed in BRCA1/2 carriers were Gleason score ≥7. The estimated positive predictive value (PPV) for PSA screening in Controls was 28%, similar to that in the general population, whilst it was 36% for BRCA1 and 46% for BRCA2. Conclusions: Our preliminary results show that annual PSA screening using a cut-off of 3.0ng/ml detects aggressive prostate cancer in BRCA carriers. Early data indicate that a larger proportion of gene carriers have developed clinically significant prostate cancers (those that would need radical treatment on UK treatment guidelines) compared with the control group. The higher risk of PrCa observed in BRCA1 and BRCA2 carriers will need to be confirmed with further data Acknowledgements: The IMPACT study collaborators and participants, The Ronald and Rita McAulay Foundation, Cancer Research UK, NIHR. Clinical trial information: NCT00261456.