Ten-year Mortality, Disease Progression, and Treatment-related Side Effects in Men with Localised Prostate Cancer from the ProtecT Randomised Controlled Trial According to Treatment Received

ProtecT Study Group, David E. Neal*, Chris Metcalfe, Jenny L. Donovan, J. Athene Lane, Michael Davis, Grace J. Young, Susan J. Dutton, Eleanor I. Walsh, Richard M. Martin, Tim J. Peters, Emma L. Turner, Malcolm Mason, Prasad Bollina, James Catto, Alan Doherty, David Gillatt, Vincent Gnanapragasam, Peter Holding, Owen HughesRoger Kockelbergh, Howard Kynaston, Jon Oxley, Alan Paul, Edgar Paez, Derek J. Rosario, Edward Rowe, John Staffurth, Doug G. Altman, Freddie C. Hamdy, Gill Lawrence, Richard Bryant

*Corresponding author for this work

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    Abstract

    Background: The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer (PCa) randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. 

    Objective: To determine report outcomes according to treatment received in men in randomised and treatment choice cohorts. 

    Design, setting, and participants: This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. 

    Intervention: Two cohorts included 1643 men who agreed to be randomised; 997 declined randomisation and chose treatment. 

    Outcome measurements and statistical analysis: Health-related quality of life impacts on urinary, bowel, and sexual function were assessed using patient-reported outcome measures. Analysis was carried out based on treatment received for each cohort and on pooled estimates using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. 

    Results and limitations: According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and outdating of the interventions being evaluated during the lengthy follow-up required in trials of screen-detected PCa. 

    Conclusions: Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. 

    Patient summary: More than 90 out of every 100 men with localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are much better after active monitoring, but the risks of spreading of prostate cancer are more common. Prostate cancer is very common, affecting about one in nine men during their lifetime, but most do not die or develop complications. The ProtecT trial randomised men with prostate-specific antigen-detected localised prostate cancer to active monitoring (AM), radical prostatectomy, or radiotherapy, and followed them up for 10 yr. We found that >90 out of every 100 men with localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring (AM), surgery, or radiotherapy. Side effects on sexual and bladder function are much better after AM than after radical treatments, but the risks of spreading of prostate cancer are greater after AM.

    Original languageEnglish
    Pages (from-to)320-330
    Number of pages11
    JournalEuropean Urology
    Volume77
    Issue number3
    DOIs
    Publication statusPublished - Mar 2020

    Bibliographical note

    Funding Information: Supported by the U.K. National Institute for Health Research Health Technology Assessment Programme (NIHR HTA: projects 96/20/06, 96/20/99, with the University of Oxford as sponsor). Dr. Donovan is supported by the NIHR Collaboration for Leadership in Applied Health Research and Care West, hosted by University Hospitals Bristol NHS Foundation Trust, and Dr. Hamdy is supported by the Oxford NIHR Biomedical Research Centre Surgical Innovation and Evaluation Theme and the Cancer Research U.K. Oxford Centre. This study was conducted in collaboration with the Bristol Randomised Trials Collaboration (BRTC), a UKCRC Registered Clinical Trials Unit, which as part of the Bristol Trials Centre is in receipt of National Institute for Health Research CTU support funding.

    Open Access: . This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

    Publisher Copyright: © 2019 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology.

    Citation: Neal, David E., et al. "Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received." European urology 77.3 (2020): 320-330.

    DOI: https://doi.org/10.1016/j.eururo.2019.10.030

    Keywords

    • Active monitoring
    • Disease progression
    • Metastasis
    • Prostate cancer
    • ProtecT trial
    • Radical prostatectomy
    • Radiotherapy

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