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

Nature Reviews Urology (2023)Cite this article

Subjects

Abstract

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.

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.

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Acknowledgements

P.R. is supported by the EUSP Scholarship of the European Association of Urology (EAU).

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Authors and Affiliations

  1. Department of Urology, Medical University of Vienna, Vienna, Austria

    Pawel Rajwa, Fahad Quhal, Benjamin Pradere & Shahrokh F. Shariat

  2. Department of Urology, Medical University of Silesia, Zabrze, Poland

    Pawel Rajwa & Andrzej Paradysz

  3. Department of Urology, King Fahad Specialist Hospital, Dammam, Saudi Arabia

    Fahad Quhal

  4. Department of Urology and Division of Experimental Oncology, Urological Research Institute, IBCAS San Raffaele Scientific Institute, Milan, Italy

    Giorgio Gandaglia & Alberto Briganti

  5. Department of Urology, La Croix du Sud Hospital, Quint Fonsegrives, France

    Guillaume Ploussard

  6. Department of Urology, Yale School of Medicine, New Haven, CT, USA

    Michael S. Leapman

  7. Department of Urology, University of Washington, Seattle Cancer Care Alliance, Seattle, WA, USA

    John L. Gore

  8. Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany

    Derya Tilki

  9. Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany

    Derya Tilki

  10. Department of Urology, Koc University Hospital, Istanbul, Turkey

    Derya Tilki

  11. Department of Urology, University Hospital Schleswig-Holstein, Lübeck, Germany

    Axel S. Merseburger

  12. Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA

    Todd M. Morgan & Ganesh S. Palapattu

  13. Institute for Urology and Reproductive Health, I. M. Sechenov First Moscow State Medical University, Moscow, Russia

    Shahrokh F. Shariat

  14. Department of Urology, Weill Cornell Medical College, New York, NY, USA

    Shahrokh F. Shariat

  15. Department of Urology, University of Texas Southwestern, Dallas, TX, USA

    Shahrokh F. Shariat

  16. Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria

    Shahrokh F. Shariat

  17. Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic

    Shahrokh F. Shariat

  18. Division of Urology, Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan

    Shahrokh F. Shariat

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P.R., F.Q. and B.P. researched data for the article. P.R., F.Q., B.P., G.G., G.P., D.T., A.S.M. and S.F.S. contributed substantially to discussion of the content. P.R., F.Q., B.P., G.G., G.P., M.S.L., A.P. and S.F.S. wrote the article. All authors reviewed and/or edited the manuscript before submission.

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Correspondence to Shahrokh F. Shariat.

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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

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