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Can we deliver randomized trials of focal therapy in prostate cancer?

Nature Reviews Clinical Oncology volume 11, pages 482–491 (2014)Cite this article

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A Corrigendum to this article was published on 12 September 2017

A Corrigendum to this article was published on 12 September 2017

This article has been updated

Abstract

Tissue-preserving focal therapies, such as brachytherapy, cryotherapy, high-intensity focused ultrasound and photodynamic therapy, aim to target individual cancer lesions rather than the whole prostate. These treatments have emerged as potential interventions for localized prostate cancer to reduce treatment-related adverse-effects associated with whole-gland treatments, such as radical prostatectomy and radiotherapy. In this article, the Prostate Cancer RCT Consensus Group propose that a novel cohort-embedded randomized controlled trial (RCT) would provide a means to study men with clinically significant localized disease, which we defined on the basis of PSA level (≤15 ng/ml or ≤20 ng/ml), Gleason grade (Gleason pattern ≤4 + 4 or ≤4 + 3) and stage (≤cT2cN0M0). This RCT should recruit men who stand to benefit from treatment, with the control arm being whole-gland surgery or radiotherapy. Composite outcomes measuring rates of local and systemic salvage therapies at 3–5 years might best constitute the basis of the primary outcome on which to change practice.

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Figure 1: Trial outlines demonstrating the essential elements of three trial designs that could deliver comparative effectiveness research in evaluating novel interventions in localized prostate cancer or other difficult-to-recruit disease areas.
Figure 2: Further answers from the cohort-embedded multiple RCT design.

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Change history

  • 12 September 2017

    Nature Reviews Clinical Oncology 11, 482–491 (2014) In the published version of this article, the affiliation and position held by Dr Viktor Berge was incorrectly stated as Professor of Urology and Director of Research at the University Hospital Oslo. Dr Berge is a Consultant Urologist at the Department of Urology, at the Oslo University Hospital.

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Acknowledgements

The Medical Research Council (UK) provided support for travel and accommodation costs to all attendees (ref G1002509). Pelican Cancer Foundation charity provided logistical support in organizing the event. No commercial bodies were involved.

Author information

Authors and Affiliations

  1. Division of Surgery, University College, London, UK

    Hashim U. Ahmed & Mark Emberton

  2. Oslo University Hospital, Oslo, Norway

    Viktor Berge

  3. St James's Institute of Oncology, Leeds, UK

    David Bottomley & William Cross

  4. Newcastle University and Freeman Hospital, Newcastle, UK

    Rakesh Heer

  5. MRC Clinical Trials Unit, London, UK

    Richard Kaplan & Matthew R. Sydes

  6. University of Oxford, Oxford, UK

    Tom Leslie

  7. Royal Marsden Hospital, London, UK

    Chris Parker

  8. University of Sheffield, Sheffield, UK

    Clare Relton

  9. National Cancer Research Institute, London, UK

    Richard Stephens

  10. University of Hull, Hull, UK

    Lindsay Turnbull

  11. London School of Hygiene and Tropical Medicine, London, UK

    Jan van der Meulen

  12. Memorial Sloan–Kettering Cancer Center, New York, USA

    Andrew Vickers

  13. University of Minnesota School of Medicine, Minnesota, USA

    Timothy Wilt

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Consortia

the Prostate Cancer RCT Consensus Group

Contributions

H.U.A. wrote the first draft. All named co-authors provided editorial input to revisions and authorized the final draft. All attendees named in Box 2 were sent the draft manuscript and had input into the drafting and editing process. All attendees gave permission to be named.

Corresponding author

Correspondence to Hashim U. Ahmed.

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Competing interests

H.U.A. has received research funding from the following companies: Advanced Medical Diagnostics, GlaxoSmithKline and Sonacare. M.E. has received research funding from the following companies: Advanced Medical Diagnostics, GlaxoSmithKline, Steba Biotech and Sonacare. M.E. is a paid consultant for GlaxoSmithKline, Steba Biotech and Sonacare. M.E. is a director on the board of and has share options in Nuada Medical. The other authors declare no competing interests.

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Supplementary Table 1

List of Protocol Development Group attendees (DOC 79 kb)

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Ahmed, H., Berge, V., Bottomley, D. et al. Can we deliver randomized trials of focal therapy in prostate cancer?. Nat Rev Clin Oncol 11, 482–491 (2014). https://doi.org/10.1038/nrclinonc.2014.44

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