Mutations in the BRCA1 and BRCA2 tumour suppressor genes are associated with prostate cancer risk; however, optimal screening protocols for individuals with these mutations have been a subject of debate. Several prospective studies of prostate cancer incidence and screening among BRCA1/2 mutation carriers have indicated at least a twofold to fourfold increase in prostate cancer risk among carriers of BRCA2 mutations compared with the general population. Moreover, BRCA2 mutations are associated with more aggressive, high-grade disease characteristics at diagnosis, more aggressive clinical behaviour and greater prostate cancer-specific mortality. The risk for BRCA1 mutations seems to be attenuated compared with BRCA2. Prostate-specific antigen (PSA) measurement or prostate magnetic resonance imaging (MRI) alone is an imperfect indicator of clinically significant prostate cancer; therefore, BRCA1/2 mutation carriers might benefit from refined risk stratification strategies. However, the long-term impact of prostate cancer screening is unknown, and the optimal management of BRCA1/2 carriers with prostate cancer has not been defined. Whether timely localized therapy can improve overall survival in the screened population is uncertain. Long-term results of prospective studies are awaited to confirm the optimal screening strategies and benefits of prostate cancer screening among BRCA1/2 mutation carriers, and whether these approaches ultimately have a positive impact on survival and quality of life in these patients.
Carriers of germline BRCA2 mutations have a twofold to fourfold higher risk of prostate cancer than the general population; for BRCA1 mutation carriers, this association is attenuated.
BRCA2 mutation carriers are more likely to be diagnosed with aggressive prostate cancer at a younger age than non-carriers.
For BRCA1/2 mutation carriers, the use of advanced prebiopsy risk stratification tools might be beneficial, instead of guideline-recommended prostate-specific antigen (PSA) testing.
PSA measurement or prostate magnetic resonance imaging (MRI) alone is inadequate for screening in BRCA1/2 mutation carriers, owing to the inherent limitations of these tests.
Screened BRCA1/2 mutation carriers might have an increased risk of prostate cancer-specific death, but these patients often develop other lethal malignancies that could limit the benefits of prostate cancer screening.
Benefits and risks of prostate cancer screening among BRCA1/2 mutation carriers must be determined and optimal early treatment strategies identified to improve quality of life and survival.
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P.R. is supported by the EUSP Scholarship of the European Association of Urology (EAU).
The authors declare no competing interests.
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Rajwa, P., Quhal, F., Pradere, B. et al. Prostate cancer risk, screening and management in patients with germline BRCA1/2 mutations. Nat Rev Urol (2023). https://doi.org/10.1038/s41585-022-00680-4