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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

Cremers, Ruben G. ; Eeles, Rosalind A. ; Bancroft, E. K. ; Ringelberg-Borsboom, Janneke ; Vasen, Hans F. ; Van Asperen, Christi J. ; Schalken, Jack A. ; Verhaegh, Gerald W. ; Kiemeney, Lambertus A. and Aaronson, N. , et al. (2015) In Urologic Oncology: Seminars and Original Investigations 33(5). p.19-202
Abstract

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 biopsies and (2) as an indicator... (More)

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 biopsies 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.

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Contribution to journal
publication status
published
subject
keywords
BRCA2, Diagnostic value, Marker, PCA3, Prostate cancer gene 3, PSA
in
Urologic Oncology: Seminars and Original Investigations
volume
33
issue
5
pages
19 - 202
publisher
Elsevier
external identifiers
  • scopus:84929266223
  • pmid:25746941
ISSN
1078-1439
DOI
10.1016/j.urolonc.2015.01.018
language
English
LU publication?
yes
id
79aa491e-8aa0-4f69-b2d8-f9427ef30dfa
date added to LUP
2020-04-23 10:09:08
date last changed
2024-01-02 09:25:01
@article{79aa491e-8aa0-4f69-b2d8-f9427ef30dfa,
  abstract     = {{<p>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 biopsies 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.</p>}},
  author       = {{Cremers, Ruben G. and Eeles, Rosalind A. and Bancroft, E. K. and Ringelberg-Borsboom, Janneke and Vasen, Hans F. and Van Asperen, Christi J. and Schalken, Jack A. and Verhaegh, Gerald W. and Kiemeney, Lambertus A. and Aaronson, N. and Ardem-Jones, A. and Bancroft, E. K. and Bangma, C. and Castro, E. and Dearnaley, D. and Eccles, D. and Eeles, R. A. and Evans, D. G. and Eyfjord, J. and Falconer, A. and Foster, C. S. and Grönberg, H. and Hamdy, F. C. and Johansson, O. and Khoo, V. and Kote-Jarai, Z. and Lilja, H. and Lubinski, J. and Maehle, L. and Melia, J. and Mikropoulos, C. and Mitchell, G. and Mitra, A. V. and Moss, S. and Moynihan, C. and Page, E. C. and Rennert, G. and Suri, M. and Wilson, P.}},
  issn         = {{1078-1439}},
  keywords     = {{BRCA2; Diagnostic value; Marker; PCA3; Prostate cancer gene 3; PSA}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{19--202}},
  publisher    = {{Elsevier}},
  series       = {{Urologic Oncology: Seminars and Original Investigations}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1016/j.urolonc.2015.01.018}},
  doi          = {{10.1016/j.urolonc.2015.01.018}},
  volume       = {{33}},
  year         = {{2015}},
}