The role of the prostate cancer gene 3 urine test in addition to serum prostate-specific antigen level in prostate cancer screening among breast cancer, early-onset gene mutation carriers.
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.


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.
Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Ruben G
RG
Cremers
The Institute of Cancer Research, London, UK; Royal Marsden Hospital NHS Foundation Trust, London, UK.
Rosalind A
RA
Eeles
The Institute of Cancer Research, London, UK; Royal Marsden Hospital NHS Foundation Trust, London, UK.
Elizabeth K
EK
Bancroft
The Netherlands Foundation for the Detection of Hereditary Tumours, Leiden, the Netherlands.
Janneke
J
Ringelberg-Borsboom
The Netherlands Foundation for the Detection of Hereditary Tumours, Leiden, the Netherlands.
Hans F
HF
Vasen
Department of Clinical Genetics, Leiden University Medical Centre, Leiden, the Netherlands.
Christi J
CJ
Van Asperen
Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Jack A
JA
Schalken
Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Gerald W
GW
Verhaegh
Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address: Bart.Kiemeney@radboudumc.nl.
Lambertus A
LA
Kiemeney
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000652:urine*; D018567:Breast Neoplasms, Male / Q000235:genetics*; D055088:Early Detection of Cancer; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017430:Prostate-Specific Antigen / Q000652:urine*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology
D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen
BRCA2; PCA3; PSA; diagnostic value; marker; prostate cancer gene 3