Effect of BRCA Mutations on Metastatic Relapse and Cause-specific Survival After Radical Treatment for Localised Prostate Cancer

2.50
Hdl Handle:
http://hdl.handle.net/11287/593933
Title:
Effect of BRCA Mutations on Metastatic Relapse and Cause-specific Survival After Radical Treatment for Localised Prostate Cancer
Authors:
Castro, E.; Goh, C.; Leongamornlert, D.; Saunders, E.; Tymrakiewicz, M.; Dadaev, T.; Govindasami, K.; Guy, M.; Ellis, S.; Frost, D.; Bancroft, E.; Cole, T.; Tischkowitz, M.; Kennedy, M. J.; Eason, J.; Brewer, Carole; Evans, D. G.; Davidson, R.; Eccles, D.; Porteous, M. E.; Douglas, F.; Adlard, J.; Donaldson, A.; Antoniou, A. C.; Kote-Jarai, Z.; Easton, D. F.; Olmos, D.; Eeles, R.
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.
Citation:
Eur Urol. 2015 Aug;68(2):186-93.
Publisher:
Elsevier
Journal:
European urology
Issue Date:
1-Aug-2015
URI:
http://hdl.handle.net/11287/593933
DOI:
10.1016/j.eururo.2014.10.022
PubMed ID:
25454609
Additional Links:
http://linkinghub.elsevier.com/retrieve/pii/S0302-2838(14)01036-7
Type:
Journal Article; Research Support, Non-U.S. Gov't
Language:
eng
ISSN:
1873-7560
Appears in Collections:
2015 RD&E publications; Clinical Genetics (Peninsula Genetics)

Full metadata record

DC FieldValue Language
dc.contributor.authorCastro, E.en
dc.contributor.authorGoh, C.en
dc.contributor.authorLeongamornlert, D.en
dc.contributor.authorSaunders, E.en
dc.contributor.authorTymrakiewicz, M.en
dc.contributor.authorDadaev, T.en
dc.contributor.authorGovindasami, K.en
dc.contributor.authorGuy, M.en
dc.contributor.authorEllis, S.en
dc.contributor.authorFrost, D.en
dc.contributor.authorBancroft, E.en
dc.contributor.authorCole, T.en
dc.contributor.authorTischkowitz, M.en
dc.contributor.authorKennedy, M. J.en
dc.contributor.authorEason, J.en
dc.contributor.authorBrewer, Caroleen
dc.contributor.authorEvans, D. G.en
dc.contributor.authorDavidson, R.en
dc.contributor.authorEccles, D.en
dc.contributor.authorPorteous, M. E.en
dc.contributor.authorDouglas, F.en
dc.contributor.authorAdlard, J.en
dc.contributor.authorDonaldson, A.en
dc.contributor.authorAntoniou, A. C.en
dc.contributor.authorKote-Jarai, Z.en
dc.contributor.authorEaston, D. F.en
dc.contributor.authorOlmos, D.en
dc.contributor.authorEeles, R.en
dc.date.accessioned2016-01-19T12:37:32Zen
dc.date.available2016-01-19T12:37:32Zen
dc.date.issued2015-08-01en
dc.identifier.citationEur Urol. 2015 Aug;68(2):186-93.en
dc.identifier.issn1873-7560en
dc.identifier.pmid25454609en
dc.identifier.doi10.1016/j.eururo.2014.10.022en
dc.identifier.urihttp://hdl.handle.net/11287/593933en
dc.description.abstractBACKGROUND: 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.en
dc.language.isoengen
dc.publisherElsevieren
dc.relation.urlhttp://linkinghub.elsevier.com/retrieve/pii/S0302-2838(14)01036-7en
dc.titleEffect of BRCA Mutations on Metastatic Relapse and Cause-specific Survival After Radical Treatment for Localised Prostate Canceren
dc.typeJournal Articleen
dc.typeResearch Support, Non-U.S. Gov'ten
dc.identifier.journalEuropean urologyen

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