Interim results from the IMPACT study: evidence for PSA screening in BRCA2 mutation carriers


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Rosalind Eeles1,Elizabeth Page2,Elizabeth Bancroft3,Mark Brook1,Melissa Assel4,Judith Offman5,Zsofia Kote-Jarai1,Andrew Vickers4,Hans Lilja4,The IMPACT study Steering Committee and IMPACT study collaborators6

1The Institute of Cancer Research, London, UK,2The Institute of Cancer Research,3Royal Marsden NHS Foundation Trust, London, UK,4Memorial Sloan Kettering Cancer Center, New York, US,5King’s College London, London, UK,6the Institute of Cancer Research

Abstract

Background

Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using PSA in men with germline BRCA1/2 mutations. The objective was to report the utility of PSA screening, PrCa incidence, positive predictive value of PSA, biopsy and tumour characteristics after three years’ screening, by BRCA status.

Method

Men aged 40–69 years with germline pathogenic BRCA1/2 mutation and male controls testing negative for a familial BRCA1/2 mutation, were recruited. Participants underwent PSA screening for three years, and if PSA >3.0ng/ml, men were offered prostate biopsy. Statistical analyses included Poisson regression offset by person-years follow-up, chi-squared tests for proportions, t-tests for means, and univariate logistic regression was applied to PSA predictors.

Results

3,027 subjects (2932 unique individuals) were recruited (919 BRCA1 carriers, 709 BRCA1 non-carriers; 902 BRCA2 carriers; 497 BRCA2 non-carriers). After 3 years screening 527 men had PSA >3.0ng/ml, 357 biopsies performed, and 112 PrCas diagnosed (31 BRCA1 carriers, 19 BRCA1 controls; 47 BRCA2 carriers, 15 BRCA2 controls). A higher compliance with biopsy was observed in BRCA2 carriers compared with controls (82% vs 66%). Cancer incidence rate per 1,000 person years was higher in BRCA2 carriers than non-carriers (19.4 vs 12.0;p=0.03); BRCA2 carriers were diagnosed younger (61 vs 64years;p=0.04) and were more likely to have clinically-significant disease than BRCA2 non-carriers (73% vs 40%;p=0.03).  No differences in age or tumour characteristics were detected between BRCA1 carriers and controls. The 4 kallikrein-marker model discriminated better (AUC=0.73) for clinically-significant cancer at biopsy than PSA alone(AUC=0.65).

Conclusion

After three years’ screening, compared with non-carriers, BRCA2 mutation carriers were associated with higher incidence of PrCa, younger age of diagnosis and clinically-significant tumours. Therefore, systematic PSA screening is indicated for men in this age group. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers.