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 & 13 others 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

*Corresponding author for this work

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)381-388
Number of pages8
JournalEuropean Urology
Volume71
Issue number3
DOIs
Publication statusPublished - 1 Mar 2017
Externally publishedYes

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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  • Cite this

    Johnston, T. J., Shaw, G. L., Lamb, A. D., Parashar, D., Greenberg, D., Xiong, T., ... 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