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 J. Rosario; Edward Rowe; Jenny L. Donovan; Freddie C. Hamdy; David E. Neal; the 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 J. Rosario, Edward Rowe, Jenny L. Donovan, Freddie C. Hamdy, David E. Neal, the ProtecT Study Group

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › 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
Early online date	6 Oct 2016
DOIs	https://doi.org/10.1016/j.eururo.2016.09.040
Publication status	Published - Mar 2017

Research Groups and Themes

BTC (Bristol Trials Centre)
BRTC
Centre for Surgical Research

Keywords

Prostate cancer
Prostate-specific antigen screening
Survival

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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., ... the 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{d4d65edfd3044037bdc77093fbe42b55,

title = "Mortality Among Men with Advanced Prostate Cancer Excluded from the ProtecT Trial",

abstract = "BackgroundEarly detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PCa) may improve survival rates.ObjectiveTo 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 participantsMortality 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 analysisPCa-specific and all-cause mortality were compared using Kaplan-Meier analysis and Cox's proportional hazards regression.Results and limitationsOf 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.ConclusionsMen 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 summaryProstate 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 Rosario, {Derek J.} and Edward Rowe and Donovan, {Jenny L.} and Hamdy, {Freddie C.} and Neal, {David E.} and {the ProtecT Study Group}",

year = "2017",

month = mar,

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

language = "English",

volume = "71",

pages = "381--388",

journal = "European Urology",

issn = "0302-2838",

publisher = "Elsevier B.V.",

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, DJ, Rowe, E, Donovan, JL, Hamdy, FC, Neal, DE & the 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 J.

AU - Rowe, Edward

AU - Donovan, Jenny L.

AU - Hamdy, Freddie C.

AU - Neal, David E.

AU - the ProtecT Study Group

PY - 2017/3

Y1 - 2017/3

N2 - BackgroundEarly detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PCa) may improve survival rates.ObjectiveTo 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 participantsMortality 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 analysisPCa-specific and all-cause mortality were compared using Kaplan-Meier analysis and Cox's proportional hazards regression.Results and limitationsOf 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.ConclusionsMen 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 summaryProstate 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 - BackgroundEarly detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PCa) may improve survival rates.ObjectiveTo 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 participantsMortality 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 analysisPCa-specific and all-cause mortality were compared using Kaplan-Meier analysis and Cox's proportional hazards regression.Results and limitationsOf 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.ConclusionsMen 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 summaryProstate 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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U2 - 10.1016/j.eururo.2016.09.040

DO - 10.1016/j.eururo.2016.09.040

M3 - Article (Academic Journal)

C2 - 27720537

SN - 0302-2838

VL - 71

SP - 381

EP - 388

JO - European Urology

JF - European Urology

IS - 3

ER -

Mortality Among Men with Advanced Prostate Cancer Excluded from the ProtecT Trial

Abstract

Research Groups and Themes

Keywords

UN SDGs

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