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

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.

Nature reviews. Urology. 2023 Jan 04 [Epub ahead of print]

Pawel Rajwa, Fahad Quhal, Benjamin Pradere, Giorgio Gandaglia, Guillaume Ploussard, Michael S Leapman, John L Gore, Andrzej Paradysz, Derya Tilki, Axel S Merseburger, Todd M Morgan, Alberto Briganti, Ganesh S Palapattu, Shahrokh F Shariat

Department of Urology, Medical University of Vienna, Vienna, Austria., Department of Urology and Division of Experimental Oncology, Urological Research Institute, IBCAS San Raffaele Scientific Institute, Milan, Italy., Department of Urology, La Croix du Sud Hospital, Quint Fonsegrives, France., Department of Urology, Yale School of Medicine, New Haven, CT, USA., Department of Urology, University of Washington, Seattle Cancer Care Alliance, Seattle, WA, USA., Department of Urology, Medical University of Silesia, Zabrze, Poland., Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany., Department of Urology, University Hospital Schleswig-Holstein, L├╝beck, Germany., Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA., Department of Urology, Medical University of Vienna, Vienna, Austria. .