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

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

doi:10.1016/j.eururo.2014.10.022

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

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

Deanery of Molecular, Genetic and Population Health Sciences

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Pages (from-to)	186-93
Number of pages	8
Journal	European Urology
Volume	68
Issue number	2
DOIs	https://doi.org/10.1016/j.eururo.2014.10.022
Publication status	Published - Aug 2015

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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, C., Evans, D. G., Davidson, R., Eccles, D., ... Eeles, R. (2015). Effect of BRCA Mutations on Metastatic Relapse and Cause-specific Survival After Radical Treatment for Localised Prostate Cancer. European Urology, 68(2), 186-93. https://doi.org/10.1016/j.eururo.2014.10.022

@article{cbfb77af35274cee86e0e3bc5093b259,

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

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.",

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

year = "2015",

month = aug,

doi = "10.1016/j.eururo.2014.10.022",

language = "English",

volume = "68",

pages = "186--93",

journal = "European Urology",

issn = "0302-2838",

publisher = "Elsevier",

number = "2",

}

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, MJ, Eason, J, Brewer, C, Evans, DG, Davidson, R, Eccles, D, Porteous, ME, Douglas, F, Adlard, J, Donaldson, A, Antoniou, AC, Kote-Jarai, Z, Easton, DF, Olmos, D & Eeles, R 2015, 'Effect of BRCA Mutations on Metastatic Relapse and Cause-specific Survival After Radical Treatment for Localised Prostate Cancer', European Urology, vol. 68, no. 2, pp. 186-93. https://doi.org/10.1016/j.eururo.2014.10.022

TY - JOUR

T1 - Effect of BRCA Mutations on Metastatic Relapse and Cause-specific Survival After Radical Treatment for Localised Prostate Cancer

AU - Castro, Elena

AU - Goh, Chee

AU - Leongamornlert, Daniel

AU - Saunders, Ed

AU - Tymrakiewicz, Malgorzata

AU - Dadaev, Tokhir

AU - Govindasami, Koveela

AU - Guy, Michelle

AU - Ellis, Steve

AU - Frost, Debra

AU - Bancroft, Elizabeth

AU - Cole, Trevor

AU - Tischkowitz, Marc

AU - Kennedy, M John

AU - Eason, Jacqueline

AU - Brewer, Carole

AU - Evans, D Gareth

AU - Davidson, Rosemarie

AU - Eccles, Diana

AU - Porteous, Mary E

AU - Douglas, Fiona

AU - Adlard, Julian

AU - Donaldson, Alan

AU - Antoniou, Antonis C

AU - Kote-Jarai, Zsofia

AU - Easton, Douglas F

AU - Olmos, David

AU - Eeles, Rosalind

PY - 2015/8

Y1 - 2015/8

N2 - 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.

AB - 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.

U2 - 10.1016/j.eururo.2014.10.022

DO - 10.1016/j.eururo.2014.10.022

M3 - Article

C2 - 25454609

SN - 0302-2838

VL - 68

SP - 186

EP - 193

JO - European Urology

JF - European Urology

IS - 2

ER -

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

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