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Effect of BRCA mutations on metastatic relapse and cause-specific survival after radical treatment for localised prostate cancer

Effect of BRCA mutations on metastatic relapse and cause-specific survival after radical treatment for localised prostate cancer
Effect of BRCA mutations on metastatic relapse and cause-specific survival after radical treatment for localised prostate cancer
BACKGROUND:
Germline BRCA mutations are associated with worse prostate cancer (PCa) outcomes; however, the most appropriate management for mutation carriers has not yet been investigated.

OBJECTIVE:
To evaluate the response of BRCA carriers to conventional treatments for localised PCa by analysing metastasis-free survival (MFS) and cause-specific survival (CSS) following radical prostatectomy (RP) or external-beam radiation therapy (RT).

DESIGN, SETTING, AND PARTICIPANTS:
Tumour features and outcomes of 1302 patients with local/locally advanced PCa (including 67 BRCA mutation carriers) were analysed. RP was undergone by 535 patients (35 BRCA); 767 received RT (32 BRCA). Median follow-up was 64 mo.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
Median survival and 3-, 5-, and 10-yr survival rates were estimated using the Kaplan-Meier method. Generated survival curves were compared using the log-rank test. Cox regression analyses were used to assess the prognostic value of BRCA mutations.

RESULTS AND LIMITATIONS:
A total of 67 BRCA carriers and 1235 noncarriers were included. At 3, 5, and 10 yr after treatment, 97%, 94%, and 84% of noncarriers and 90%, 72%, and 50% of carriers were free from metastasis (p<0.001). The 3-, 5- and 10-yr CSS rates were significantly better in the noncarrier cohort (99%, 97%, and 85%, respectively) than in carriers (96%, 76%, and 61%, respectively; p<0.001). Multivariate analysis confirmed BRCA mutations as an independent prognostic factor for MFS (hazard ratio [HR]: 2.36; 95% confidence interval [CI], 1.38-4.03; p=0.002) and CSS (HR: 2.17; 95% CI, 1.16-4.07; p=0.016).

CONCLUSIONS:
BRCA carriers had worse outcomes than noncarriers when conventionally treated for local/locally advanced PCa.

PATIENT SUMMARY:
Prostate cancer patients with germline BRCA mutations had worse outcomes than noncarriers when conventionally treated with surgery or radiation therapy.
brca1, brca2, homologous repair, prognostic factor, prostate cancer, prostatectomy, radiotherapy
0302-2838
186-193
Castro, Elena
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Goh, Chee
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Leongamornlert, Daniel
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Saunders, Ed
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Tymrakiewicz, Malgorzata
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Dadaev, Tokhir
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Govindasami, Koveela
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Guy, Michelle
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Ellis, Steve
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Frost, Debra
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Bancroft, Elizabeth
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Cole, Trevor
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Tischkowitz, Marc
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Kennedy, M. John
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Eason, Jacqueline
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Brewer, Carole
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Evans, D. Gareth
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Davidson, Rosemarie
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Eccles, Diana
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Porteous, Mary E.
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Douglas, Fiona
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Adlard, Julian
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Donaldson, Alan
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Antoniou, Antonis C.
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Kote-Jarai, Zsofia
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Easton, Douglas F.
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Olmos, David
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Eeles, Rosalind
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Castro, Elena
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Goh, Chee
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Leongamornlert, Daniel
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Saunders, Ed
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Tymrakiewicz, Malgorzata
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Dadaev, Tokhir
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Govindasami, Koveela
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Guy, Michelle
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Ellis, Steve
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Frost, Debra
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Bancroft, Elizabeth
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Cole, Trevor
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Tischkowitz, Marc
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Kennedy, M. John
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Eason, Jacqueline
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Brewer, Carole
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Evans, D. Gareth
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Davidson, Rosemarie
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Eccles, Diana
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Adlard, Julian
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Donaldson, Alan
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Antoniou, Antonis C.
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Kote-Jarai, Zsofia
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Easton, Douglas F.
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Olmos, David
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Eeles, Rosalind
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Castro, Elena, Goh, Chee and Leongamornlert, Daniel et al. (2015) Effect of BRCA mutations on metastatic relapse and cause-specific survival after radical treatment for localised prostate cancer. European Urology, 68 (2), 186-193. (doi:10.1016/j.eururo.2014.10.022). (PMID:25454609)

Record type: Article

Abstract

BACKGROUND:
Germline BRCA mutations are associated with worse prostate cancer (PCa) outcomes; however, the most appropriate management for mutation carriers has not yet been investigated.

OBJECTIVE:
To evaluate the response of BRCA carriers to conventional treatments for localised PCa by analysing metastasis-free survival (MFS) and cause-specific survival (CSS) following radical prostatectomy (RP) or external-beam radiation therapy (RT).

DESIGN, SETTING, AND PARTICIPANTS:
Tumour features and outcomes of 1302 patients with local/locally advanced PCa (including 67 BRCA mutation carriers) were analysed. RP was undergone by 535 patients (35 BRCA); 767 received RT (32 BRCA). Median follow-up was 64 mo.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
Median survival and 3-, 5-, and 10-yr survival rates were estimated using the Kaplan-Meier method. Generated survival curves were compared using the log-rank test. Cox regression analyses were used to assess the prognostic value of BRCA mutations.

RESULTS AND LIMITATIONS:
A total of 67 BRCA carriers and 1235 noncarriers were included. At 3, 5, and 10 yr after treatment, 97%, 94%, and 84% of noncarriers and 90%, 72%, and 50% of carriers were free from metastasis (p<0.001). The 3-, 5- and 10-yr CSS rates were significantly better in the noncarrier cohort (99%, 97%, and 85%, respectively) than in carriers (96%, 76%, and 61%, respectively; p<0.001). Multivariate analysis confirmed BRCA mutations as an independent prognostic factor for MFS (hazard ratio [HR]: 2.36; 95% confidence interval [CI], 1.38-4.03; p=0.002) and CSS (HR: 2.17; 95% CI, 1.16-4.07; p=0.016).

CONCLUSIONS:
BRCA carriers had worse outcomes than noncarriers when conventionally treated for local/locally advanced PCa.

PATIENT SUMMARY:
Prostate cancer patients with germline BRCA mutations had worse outcomes than noncarriers when conventionally treated with surgery or radiation therapy.

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More information

Accepted/In Press date: 15 October 2014
e-pub ahead of print date: 6 November 2014
Published date: August 2015
Keywords: brca1, brca2, homologous repair, prognostic factor, prostate cancer, prostatectomy, radiotherapy
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 382466
URI: https://eprints.soton.ac.uk/id/eprint/382466
ISSN: 0302-2838
PURE UUID: 3046bc6b-a39b-4111-b143-27d882360428

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Date deposited: 05 Oct 2015 12:50
Last modified: 15 Jul 2019 21:02

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Contributors

Author: Elena Castro
Author: Chee Goh
Author: Daniel Leongamornlert
Author: Ed Saunders
Author: Malgorzata Tymrakiewicz
Author: Tokhir Dadaev
Author: Koveela Govindasami
Author: Michelle Guy
Author: Steve Ellis
Author: Debra Frost
Author: Elizabeth Bancroft
Author: Trevor Cole
Author: Marc Tischkowitz
Author: M. John Kennedy
Author: Jacqueline Eason
Author: Carole Brewer
Author: D. Gareth Evans
Author: Rosemarie Davidson
Author: Diana Eccles
Author: Mary E. Porteous
Author: Fiona Douglas
Author: Julian Adlard
Author: Alan Donaldson
Author: Antonis C. Antoniou
Author: Zsofia Kote-Jarai
Author: Douglas F. Easton
Author: David Olmos
Author: Rosalind Eeles

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