Mortality among men with advanced prostate cancer excluded from the ProtecT trial

Thomas J. Johnston; Greg L. Shaw; Alastair D. Lamb; Deepak Parashar; David Greenberg; Tengbin Xiong; Alison L. Edwards; Vincent Gnanapragasam; Peter Holding; Phillipa Herbert; Michael Davis; Elizabeth Mizielinsk; J. Athene Lane; Jon Oxley; Mary Robinson; Malcolm Mason; John Staffurth; Prasad Bollina; James Catto; Andrew Doble; Alan Doherty; David Gillatt; Roger Kockelbergh; Howard Kynaston; Steve Prescott; Alan Paul; Philip Powell; Derek Rosario; Edward Rowe; Jenny L. Donovan; Freddie C. Hamdy; David E. Neal; ProtecT Study Group

doi:10.1016/j.eururo.2016.09.040

Mortality among men with advanced prostate cancer excluded from the ProtecT trial

Thomas J. Johnston^*, Greg L. Shaw, Alastair D. Lamb, Deepak Parashar, David Greenberg, Tengbin Xiong, Alison L. Edwards, Vincent Gnanapragasam, Peter Holding, Phillipa Herbert, Michael Davis, Elizabeth Mizielinsk, J. Athene Lane, Jon Oxley, Mary Robinson, Malcolm Mason, John Staffurth, Prasad Bollina, James Catto, Andrew DobleAlan Doherty, David Gillatt, Roger Kockelbergh, Howard Kynaston, Steve Prescott, Alan Paul, Philip Powell, Derek Rosario, Edward Rowe, Jenny L. Donovan, Freddie C. Hamdy, David E. Neal, ProtecT Study Group

^*Corresponding author for this work

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

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Abstract

Background: Early detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PCa) may improve survival rates.

Objective: To determine outcomes for men diagnosed with advanced PCa following prostate-specific antigen (PSA) testing who were excluded from the ProtecT randomised trial.

Design, setting, and participants: Mortality was compared for 492 men followed up for a median of 7.4 yr to a contemporaneous cohort of men from the UK Anglia Cancer Network (ACN) and with a matched subset from the ACN.

Outcome measurements and statistical analysis: PCa-specific and all-cause mortality were compared using Kaplan-Meier analysis and Cox's proportional hazards regression.

Results and limitations: Of the 492 men excluded from the ProtecT cohort, 37 (8%) had metastases (N1, M0 = 5, M1 = 32) and 305 had locally advanced disease (62%). The median PSA was 17 μg/l. Treatments included radical prostatectomy (RP; n = 54; 11%), radiotherapy (RT; n = 245; 50%), androgen deprivation therapy (ADT; n = 122; 25%), other treatments (n = 11; 2%), and unknown (n = 60; 12%). There were 49 PCa-specific deaths (10%), of whom 14 men had received radical treatment (5%); and 129 all-cause deaths (26%). In matched ProtecT and ACN cohorts, 37 (9%) and 64 (16%), respectively, died of PCa, while 89 (22%) and 103 (26%) died of all causes. ProtecT men had a 45% lower risk of death from PCa compared to matched cases (hazard ratio 0.55, 95% confidence interval 0.38–0.83; p = 0.0037), but mortality was similar in those treated radically. The nonrandomised design is a limitation.

Conclusions: Men with PSA-detected advanced PCa excluded from ProtecT and treated radically had low rates of PCa death at 7.4-yr follow-up. Among men who underwent nonradical treatment, the ProtecT group had a lower rate of PCa death. Early detection through PSA testing, leadtime bias, and group heterogeneity are possible factors in this finding.

Patient summary: Prostate cancer that has spread outside the prostate gland without causing symptoms can be detected via prostate-specific antigen testing and treated, leading to low rates of death from this disease.

Original language	English
Pages (from-to)	381-388
Number of pages	8
Journal	European Urology
Volume	71
Issue number	3
DOIs	https://doi.org/10.1016/j.eururo.2016.09.040
Publication status	Published - 1 Mar 2017
Externally published	Yes

Bibliographical note

Copyright the European Association of Urology 2016. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

Prostate cancer
Prostate-specific antigen screening
Survival

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10.1016/j.eururo.2016.09.040

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Johnston, T. J., Shaw, G. L., Lamb, A. D., Parashar, D., Greenberg, D., Xiong, T., Edwards, A. L., Gnanapragasam, V., Holding, P., Herbert, P., Davis, M., Mizielinsk, E., Lane, J. A., Oxley, J., Robinson, M., Mason, M., Staffurth, J., Bollina, P., Catto, J., ... ProtecT Study Group (2017). Mortality among men with advanced prostate cancer excluded from the ProtecT trial. European Urology, 71(3), 381-388. https://doi.org/10.1016/j.eururo.2016.09.040

@article{cd95b67a94e44f948d12e90b0ec0025a,

title = "Mortality among men with advanced prostate cancer excluded from the ProtecT trial",

abstract = "Background: Early detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PCa) may improve survival rates. Objective: To determine outcomes for men diagnosed with advanced PCa following prostate-specific antigen (PSA) testing who were excluded from the ProtecT randomised trial. Design, setting, and participants: Mortality was compared for 492 men followed up for a median of 7.4 yr to a contemporaneous cohort of men from the UK Anglia Cancer Network (ACN) and with a matched subset from the ACN. Outcome measurements and statistical analysis: PCa-specific and all-cause mortality were compared using Kaplan-Meier analysis and Cox's proportional hazards regression. Results and limitations: Of the 492 men excluded from the ProtecT cohort, 37 (8%) had metastases (N1, M0 = 5, M1 = 32) and 305 had locally advanced disease (62%). The median PSA was 17 μg/l. Treatments included radical prostatectomy (RP; n = 54; 11%), radiotherapy (RT; n = 245; 50%), androgen deprivation therapy (ADT; n = 122; 25%), other treatments (n = 11; 2%), and unknown (n = 60; 12%). There were 49 PCa-specific deaths (10%), of whom 14 men had received radical treatment (5%); and 129 all-cause deaths (26%). In matched ProtecT and ACN cohorts, 37 (9%) and 64 (16%), respectively, died of PCa, while 89 (22%) and 103 (26%) died of all causes. ProtecT men had a 45% lower risk of death from PCa compared to matched cases (hazard ratio 0.55, 95% confidence interval 0.38–0.83; p = 0.0037), but mortality was similar in those treated radically. The nonrandomised design is a limitation. Conclusions: Men with PSA-detected advanced PCa excluded from ProtecT and treated radically had low rates of PCa death at 7.4-yr follow-up. Among men who underwent nonradical treatment, the ProtecT group had a lower rate of PCa death. Early detection through PSA testing, leadtime bias, and group heterogeneity are possible factors in this finding. Patient summary: Prostate cancer that has spread outside the prostate gland without causing symptoms can be detected via prostate-specific antigen testing and treated, leading to low rates of death from this disease.",

keywords = "Prostate cancer, Prostate-specific antigen screening, Survival",

author = "Johnston, {Thomas J.} and Shaw, {Greg L.} and Lamb, {Alastair D.} and Deepak Parashar and David Greenberg and Tengbin Xiong and Edwards, {Alison L.} and Vincent Gnanapragasam and Peter Holding and Phillipa Herbert and Michael Davis and Elizabeth Mizielinsk and Lane, {J. Athene} and Jon Oxley and Mary Robinson and Malcolm Mason and John Staffurth and Prasad Bollina and James Catto and Andrew Doble and Alan Doherty and David Gillatt and Roger Kockelbergh and Howard Kynaston and Steve Prescott and Alan Paul and Philip Powell and Derek Rosario and Edward Rowe and Donovan, {Jenny L.} and Hamdy, {Freddie C.} and Neal, {David E.} and {ProtecT Study Group}",

note = "Copyright the European Association of Urology 2016. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

year = "2017",

month = mar,

day = "1",

doi = "10.1016/j.eururo.2016.09.040",

language = "English",

volume = "71",

pages = "381--388",

journal = "European Urology",

issn = "0302-2838",

publisher = "Elsevier",

number = "3",

}

Johnston, TJ, Shaw, GL, Lamb, AD, Parashar, D, Greenberg, D, Xiong, T, Edwards, AL, Gnanapragasam, V, Holding, P, Herbert, P, Davis, M, Mizielinsk, E, Lane, JA, Oxley, J, Robinson, M, Mason, M, Staffurth, J, Bollina, P, Catto, J, Doble, A, Doherty, A, Gillatt, D, Kockelbergh, R, Kynaston, H, Prescott, S, Paul, A, Powell, P, Rosario, D, Rowe, E, Donovan, JL, Hamdy, FC, Neal, DE & ProtecT Study Group 2017, 'Mortality among men with advanced prostate cancer excluded from the ProtecT trial', European Urology, vol. 71, no. 3, pp. 381-388. https://doi.org/10.1016/j.eururo.2016.09.040

TY - JOUR

T1 - Mortality among men with advanced prostate cancer excluded from the ProtecT trial

AU - Johnston, Thomas J.

AU - Shaw, Greg L.

AU - Lamb, Alastair D.

AU - Parashar, Deepak

AU - Greenberg, David

AU - Xiong, Tengbin

AU - Edwards, Alison L.

AU - Gnanapragasam, Vincent

AU - Holding, Peter

AU - Herbert, Phillipa

AU - Davis, Michael

AU - Mizielinsk, Elizabeth

AU - Lane, J. Athene

AU - Oxley, Jon

AU - Robinson, Mary

AU - Mason, Malcolm

AU - Staffurth, John

AU - Bollina, Prasad

AU - Catto, James

AU - Doble, Andrew

AU - Doherty, Alan

AU - Gillatt, David

AU - Kockelbergh, Roger

AU - Kynaston, Howard

AU - Prescott, Steve

AU - Paul, Alan

AU - Powell, Philip

AU - Rosario, Derek

AU - Rowe, Edward

AU - Donovan, Jenny L.

AU - Hamdy, Freddie C.

AU - Neal, David E.

AU - ProtecT Study Group

N1 - Copyright the European Association of Urology 2016. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Background: Early detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PCa) may improve survival rates. Objective: To determine outcomes for men diagnosed with advanced PCa following prostate-specific antigen (PSA) testing who were excluded from the ProtecT randomised trial. Design, setting, and participants: Mortality was compared for 492 men followed up for a median of 7.4 yr to a contemporaneous cohort of men from the UK Anglia Cancer Network (ACN) and with a matched subset from the ACN. Outcome measurements and statistical analysis: PCa-specific and all-cause mortality were compared using Kaplan-Meier analysis and Cox's proportional hazards regression. Results and limitations: Of the 492 men excluded from the ProtecT cohort, 37 (8%) had metastases (N1, M0 = 5, M1 = 32) and 305 had locally advanced disease (62%). The median PSA was 17 μg/l. Treatments included radical prostatectomy (RP; n = 54; 11%), radiotherapy (RT; n = 245; 50%), androgen deprivation therapy (ADT; n = 122; 25%), other treatments (n = 11; 2%), and unknown (n = 60; 12%). There were 49 PCa-specific deaths (10%), of whom 14 men had received radical treatment (5%); and 129 all-cause deaths (26%). In matched ProtecT and ACN cohorts, 37 (9%) and 64 (16%), respectively, died of PCa, while 89 (22%) and 103 (26%) died of all causes. ProtecT men had a 45% lower risk of death from PCa compared to matched cases (hazard ratio 0.55, 95% confidence interval 0.38–0.83; p = 0.0037), but mortality was similar in those treated radically. The nonrandomised design is a limitation. Conclusions: Men with PSA-detected advanced PCa excluded from ProtecT and treated radically had low rates of PCa death at 7.4-yr follow-up. Among men who underwent nonradical treatment, the ProtecT group had a lower rate of PCa death. Early detection through PSA testing, leadtime bias, and group heterogeneity are possible factors in this finding. Patient summary: Prostate cancer that has spread outside the prostate gland without causing symptoms can be detected via prostate-specific antigen testing and treated, leading to low rates of death from this disease.

AB - Background: Early detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PCa) may improve survival rates. Objective: To determine outcomes for men diagnosed with advanced PCa following prostate-specific antigen (PSA) testing who were excluded from the ProtecT randomised trial. Design, setting, and participants: Mortality was compared for 492 men followed up for a median of 7.4 yr to a contemporaneous cohort of men from the UK Anglia Cancer Network (ACN) and with a matched subset from the ACN. Outcome measurements and statistical analysis: PCa-specific and all-cause mortality were compared using Kaplan-Meier analysis and Cox's proportional hazards regression. Results and limitations: Of the 492 men excluded from the ProtecT cohort, 37 (8%) had metastases (N1, M0 = 5, M1 = 32) and 305 had locally advanced disease (62%). The median PSA was 17 μg/l. Treatments included radical prostatectomy (RP; n = 54; 11%), radiotherapy (RT; n = 245; 50%), androgen deprivation therapy (ADT; n = 122; 25%), other treatments (n = 11; 2%), and unknown (n = 60; 12%). There were 49 PCa-specific deaths (10%), of whom 14 men had received radical treatment (5%); and 129 all-cause deaths (26%). In matched ProtecT and ACN cohorts, 37 (9%) and 64 (16%), respectively, died of PCa, while 89 (22%) and 103 (26%) died of all causes. ProtecT men had a 45% lower risk of death from PCa compared to matched cases (hazard ratio 0.55, 95% confidence interval 0.38–0.83; p = 0.0037), but mortality was similar in those treated radically. The nonrandomised design is a limitation. Conclusions: Men with PSA-detected advanced PCa excluded from ProtecT and treated radically had low rates of PCa death at 7.4-yr follow-up. Among men who underwent nonradical treatment, the ProtecT group had a lower rate of PCa death. Early detection through PSA testing, leadtime bias, and group heterogeneity are possible factors in this finding. Patient summary: Prostate cancer that has spread outside the prostate gland without causing symptoms can be detected via prostate-specific antigen testing and treated, leading to low rates of death from this disease.

KW - Prostate cancer

KW - Prostate-specific antigen screening

KW - Survival

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DO - 10.1016/j.eururo.2016.09.040

M3 - Article

C2 - 27720537

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SN - 0302-2838

VL - 71

SP - 381

EP - 388

JO - European Urology

JF - European Urology

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ER -

Mortality among men with advanced prostate cancer excluded from the ProtecT trial

Abstract

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Keywords

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