RESUMO
OBJECTIVE: To evaluate the additive value of the prostate cancer gene 3 (PCA3) urine test to serum prostate-specific antigen (PSA) in prostate cancer (PC) screening among breast cancer, early-onset gene (BRCA) mutation carriers. This study was performed among the Dutch participants of IMPACT, a large international study on the effectiveness of PSA screening among BRCA mutation carriers. MATERIALS AND METHODS: Urinary PCA3 was measured in 191 BRCA1 mutation carriers, 75 BRCA2 mutation carriers, and 308 noncarriers. The physicians and participants were blinded for the results. Serum PSA level ≥ 3.0 ng/ml was used to indicate prostate biopsies. PCA3 was evaluated (1) as an independent indicator for prostate b iopsies and (2) as an indicator for prostate biopsies among men with an elevated PSA level. PC detected up to the 2-year screening was used as gold standard as end-of-study biopsies were not performed. RESULTS: Overall, 23 PCs were diagnosed, 20 of which were in men who had an elevated PSA level in the initial screening round. (1) PCA3, successfully determined in 552 participants, was elevated in 188 (cutoff ≥ 25; 34%) or 134 (cutoff ≥ 35; 24%) participants, including 2 of the 3 PCs missed by PSA. PCA3 would have added 157 (≥ 25; 28%) or 109 (≥ 35; 20%) biopsy sessions to screening with PSA only. (2) Elevated PCA3 as a requirement for biopsies in addition to PSA would have saved 37 (cutoff ≥ 25) or 43 (cutoff ≥ 35) of the 68 biopsy sessions, and 7 or 11 PCs would have been missed, respectively, including multiple high-risk PCs. So far, PCA3 performed best among BRCA2 mutation carriers, but the numbers are still small. Because PCA3 was not used to indicate prostate biopsies, its true diagnostic value cannot be calculated. CONCLUSIONS: The results do not provide evidence for PCA3 as a useful additional indicator of prostate biopsies in BRCA mutation carriers, as many participants had an elevated PCA3 in the absence of PC. This must be interpreted with caution because PCA3 was not used to indicate biopsies. Many participants diagnosed with PC had low PCA3, making it invalid as a restrictive marker for prostate biopsies in men with elevated PSA levels.