IMPACT data support PSA screening in BRCA2 mutation carriers
medwireNews: Men with a BRCA2 mutation are more likely to be diagnosed with prostate cancer following annual prostate-specific antigen (PSA) screening than men without the mutation, interim results from the multinational IMPACT study show.
Furthermore, the study published in European Urology found that BRCA2 mutation carriers were diagnosed at a younger age and were more likely to have clinically significant disease at diagnosis than noncarriers.
Rosalind Eeles (Institute of Cancer Research, London, UK) and co-investigators say their data therefore “support the use of systematic PSA screening in male BRCA2 carriers.”
Over four rounds of PSA screening, 527 (18%) of the 2932 IMPACT study participants, who were aged between 40 and 69 years, had a PSA above 3.0 ng/mL. These men were all offered biopsies, of whom 357 accepted, resulting in 112 prostate cancer cases being diagnosed. This gave an overall detection rate of 3.8% and an incidence of 15 cases per 1000 person–years.
Prostate cancer was diagnosed in 3.4% of the 919 BRCA1 mutation carriers, 2.7% of the 709 BRCA1 wild-type patients, 5.2% of 902 BRCA2 mutation carriers and 3.0% of 497 BRCA2 wild-type patients.
Prostate cancer incidence was significantly higher in BRCA2 carriers than in noncarriers at 19 versus 12 cases per 1000 person–years, but there was no significant difference in incidence between BRCA1 carriers and noncarriers (14 vs 11 cases per 1000 person–years).
The overall positive predictive value (PPV) of a PSA result above 3.0 ng/mL for prostate cancer was 21%, but it was significantly higher in BRCA2 carriers relative to noncarriers, at 31% versus 18%. By contrast there was no significant difference in PPV for PSA screening between BRCA1 carriers and noncarriers, at 23% versus 15%.
Eeles and team calculated that 60 BRCA2 carriers aged 40–54 years, and 13 carriers aged 55–69 years would need to be screened for four rounds to detect one case of prostate cancer.
The researchers also found that BRCA2 carriers were diagnosed at a significantly younger age than noncarriers (mean 61 vs 64 years) and were significantly more likely to have clinically significant intermediate- or high-risk disease than noncarriers (77% vs 40%).
Conversely, there were no significant differences in age or tumor characteristics between BRCA1 carriers and noncarriers.
Eeles and co-authors say their findings strengthen those observed in their previously published baseline analysis.
They add that the IMPACT study continues to collect data and will offer all men an opportunity to undergo prostate biopsy after five years of screening.
The team concludes: “This will provide the opportunity to evaluate the number of clinically significant cancers missed in carriers and non-carriers when using a PSA threshold of 3.0 ng/ml.”
By Laura Cowen
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