Prostate-specific antigen screening at low thresholds of men with pathogenic BRCA1/2 variants

BACKGROUND: Men with pathogenic BRCA1/2 variants are at higher risk of prostate cancer We included men with likely pathogenic/pathogenic (LP/P) variants in BRCA1/2 in a prostate-specific antigen (PSA) screening program after cascade germline testing since 2014. PSA was tested yearly and an age-specific low PSA threshold for biopsy was used, to determine if a low PSA threshold for biopsy is justified for men with pathogenic BRCA1/2 variants.

METHODS: From 2014 to 2023 a total of 340 men were included in the program. We report demographics, clinical characteristics, and treatment outcomes at 7 years.

RESULTS: The cumulative incidence of a primary biopsy was 37% (95CI: 31‒43) after 7 years. Incidence of prostate cancer diagnosis was 11% (95CI: 7.1‒15). Men referred were 7.8 (95CI: 5.3‒11, p < 0.001) times more likely to be diagnosed with prostate cancer than the general Danish male population. The cumulative incidence of biochemical failure (PSA > = 0.2 ng/ml) 4 years after RP was 22% (95CI: 2.3‒41). The main limitation is that not all men underwent a pre-biopsy MRI.

CONCLUSION: We found a high incidence of prostate cancer in men with LP/P BRCA1/2 variants, but this may be explained by the low PSA threshold for scheduling biopsies. More studies are needed to compare this patient population to men with other germline features. The high risk of recurrence after curative therapy is worrisome and requires further evaluation as to whether this is a biological phenomenon.