Prostate cancer risk, screening and management in patients with germline BRCA1/2 mutations

• Published in: Nature reviews. Urology Vol. 20; no. 4; pp. 205 - 216
• Main Authors: Rajwa, Pawel, Quhal, Fahad, Pradere, Benjamin, Gandaglia, Giorgio, Ploussard, Guillaume, Leapman, Michael S., Gore, John L., Paradysz, Andrzej, Tilki, Derya, Merseburger, Axel S., Morgan, Todd M., Briganti, Alberto, Palapattu, Ganesh S., Shariat, Shahrokh F.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2023; Nature Publishing Group
• Subjects: 631/67/2322; 692/4025/1752; 692/4028/67/2322; 692/4028/67/589/466; BRCA1 Protein - genetics; BRCA2 Protein - genetics; Early Detection of Cancer - methods; Genes, BRCA1; Genetic Predisposition to Disease; Germ Cells - pathology; Humans; Male; Medical screening; Medicine; Medicine & Public Health; Mutation; Prospective Studies; Prostate cancer; Prostate-Specific Antigen - genetics; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - genetics; Prostatic Neoplasms - therapy; Quality of Life; Review Article; Urology
• ISSN: 1759-4812; 1759-4820; 1759-4820
• DOI: 10.1038/s41585-022-00680-4

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. Mutations in the BRCA1 and BRCA2 tumour suppressor genes are associated with prostate cancer risk, but optimal screening protocols for individuals with these mutations have been a subject of debate. In this Review, the authors discuss the risk associated with BRCA 1/2 mutations and consider how, and whether, a screening programme should be implemented for these individuals. Key points 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.