Targeted Prostate Cancer Screening in BRCA1 and BRCA2 Mutation Carriers: Results from the Initial Screening Round of the IMPACT Study

Abstract

BackgroundMen with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international consortium of 62 centres in 20 countries evaluating the use of targeted PCa screening in men with BRCA1/2 mutations.ObjectiveTo report the first year's screening results for all men at enrolment in the study.Design, setting and participantsWe recruited men aged 40–69 yr with germline BRCA1/2 mutations and a control group of men who have tested negative for a pathogenic BRCA1 or BRCA2 mutation known to be present in their families. All men underwent prostate-specific antigen (PSA) testing at enrolment, and those men with PSA >3 ng/ml were offered prostate biopsy.Outcome measurements and statistical analysisPSA levels, PCa incidence, and tumour characteristics were evaluated. The Fisher exact test was used to compare the number of PCa cases among groups and the differences among disease types.Results and limitationsWe recruited 2481 men (791 BRCA1 carriers, 531 BRCA1 controls; 731 BRCA2 carriers, 428 BRCA2 controls). A total of 199 men (8%) presented with PSA >3.0 ng/ml, 162 biopsies were performed, and 59 PCas were diagnosed (18 BRCA1 carriers, 10 BRCA1 controls; 24 BRCA2 carriers, 7 BRCA2 controls); 66% of the tumours were classified as intermediate- or high-risk disease. The positive predictive value (PPV) for biopsy using a PSA threshold of 3.0 ng/ml in BRCA2 mutation carriers was 48%—double the PPV reported in population screening studies. A significant difference in detecting intermediate- or high-risk disease was observed in BRCA2 carriers. Ninety-five percent of the men were white, thus the results cannot be generalised to all ethnic groups.ConclusionsThe IMPACT screening network will be useful for targeted PCa screening studies in men with germline genetic risk variants as they are discovered. These preliminary results support the use of targeted PSA screening based on BRCA genotype and show that this screening yields a high proportion of aggressive disease.Patient summaryIn this report, we demonstrate that germline genetic markers can be used to identify men at higher risk of prostate cancer. Targeting screening at these men resulted in the identification of tumours that were more likely to require treatment.

Erratum: Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition

“…The design and eligibility criteria for the IMPACT study have been described elsewhere (Mitra et al, 2008;Bancroft et al, 2014). The protocol was approved by the WestMidlands Research and Ethics Committee in the UK (reference 05/ MRE07/25), and subsequently by each participating institution's local committee.…”

EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent

“…About 9% of men with PCa have truly hereditary disease, which is associated with an onset six to seven years earlier than spontaneous cases, but the biology does not differ. The only exception are carriers of the rare BRCA2 germline abnormality, who seem to have an increased risk of early-onset PCa with aggressive behaviour [9][10][11].…”

Kanserde erken tanı ve tarama programları

“…Prostat kanseri açısından risk oluşturan durumlar; siyah ırk, ailede özellikle65 yaşından önce prostat kanseri tanısının olması, bilinen BRCA1/BRCA2 gen mutasyonunun varlığıdır (20,21). Riskli grupta 40-45 yaşından itibaren taramaya başlanması önerilmektedir.…”