Clinical Management of Prostate Cancer in Men with BRCA Mutations.

This issue of European Urology includes a report on the outcome after local prostate cancer (PCa) treatment in men with mutations in the cancer susceptibility gene breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) [1]. Germline mutations in these genes confer a much higher risk of breast and ovarian cancers in women and, to a somewhat lesser degree, PCa and other cancers in men [2,3]. In female BRCA carriers, breast cancer screening and risk-reducing prophylactic surgery have documented effects on breast and ovarian cancer morbidity and mortality [2]. In comparison, the scientific basis for the management of male BRCA mutation carriers is poor, and the present report by Castro and co-workers is therefore welcome. They analysed the outcome for 67 BRCAmutation carriers and 1235 noncarriers with PCa treated with either radical prostatectomy or radiotherapy, and found that the rates of metastatic disease and death from PCa were significantly higher among BRCA carriers [1]. A BRCA mutation was an independent negative prognostic factor, even after adjusting for cancer grade, stage, and prostatespecific antigen (PSA) level in multivariate analysis. What are the clinical implications of the results from this and other studies on germline BRCA mutations in men with and without PCa? The first step is to always obtain a thorough cancer family history from our PCa patients and in men with increased PSA levels. A germline BRCA mutation should be suspected in families withmultiple cases of earlyonset prostate, breast, and/or ovarian cancer. Such families should be offered appropriate oncogenetic counselling, including molecular genetic diagnostic tests [2,3]. Second, since male unaffected BRCA2 mutation carriers clearly have a much higher risk of early-onset, aggressive PCa [3–5], they should be recommended PSA testing from the age of 40 yr [6]. Remarkably high PCa mortality following standard screening with PSA and digital rectal examination has been reported for men with BRCA2 mutations [5], indicating that the screening intervals should be shorter and the PSA thresholds lower for them than for men in the general population. The reports are less consistent regarding the PCa risk and phenotype in BRCA1 mutation carriers [3]. A reasonable approach is to inform male BRCA1 mutation carriers that they may have a significantly higher risk of PCa and to offer them PSA testing from the age of 40 yr. The PCa detection rate following screening of male BRCA mutation carriers was recently reported in European Urology [6]. Further reports from this important prospective study are eagerly awaited, not least for the possible different impact of BRCA1 and BRCA2 mutations on PCa risk and phenotype. Third, radical local therapy should be initiated early when PCa is diagnosed in BRCAmutation carriers, at least in BRCA2 mutation carriers. Active surveillance may not be safe, even for a very low-risk PCa, in these men. Castro and co-workers report that a BRCA mutation is an independent negative prognostic factor after treatment with either radical prostatectomy or radiotherapy [1]. They did not report the outcome of BRCA1 and BRCA2 mutation carriers separately, presumably because there were too few men in each group. Their results, together with the poor outcome of PCa screening in BRCA2 mutation carriers [5], highlight a need to combine local treatment with adjuvant systemic therapy. However, there is no evidence indicating that adjuvant therapy decreases mortality in this group of patients, or indeed in any other group of PCa patients. Since EU RO P E AN URO L OG Y 6 8 ( 2 0 1 5 ) 1 9 4 – 1 9 5