Partial ablation versus radical prostatectomy in intermediate-risk prostate cancer: the PART feasibility RCT
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background
Prostate cancer (PCa) is the most common cancer in men in the UK. Patients with intermediate-risk, clinically localised disease are offered radical treatments such as surgery or radiotherapy, which can result in severe side effects. A number of alternative partial ablation (PA) technologies that may reduce treatment burden are available; however the comparative effectiveness of these techniques has never been evaluated in a randomised controlled trial (RCT).
Objectives
To assess the feasibility of a RCT of PA using high-intensity focused ultrasound (HIFU) versus radical prostatectomy (RP) for intermediate-risk PCa and to test and optimise methods of data capture.
Design
We carried out a prospective, multicentre, open-label feasibility study to inform the design and conduct of a future RCT, involving a QuinteT Recruitment Intervention (QRI) to understand barriers to participation.
Setting
Five NHS hospitals in England.
Participants
Men with unilateral, intermediate-risk, clinically localised PCa.
Interventions
Radical prostatectomy compared with HIFU.
Primary outcome measure
The randomisation of 80 men.
Secondary outcome measures
Findings of the QRI and assessment of data capture methods.
Results
Eighty-seven patients consented to participate by 31 March 2017 and 82 men were randomised by 4 May 2017 (41 men to the RP arm and 41 to the HIFU arm). The QRI was conducted in two iterative phases: phase I identified a number of barriers to recruitment, including organisational challenges, lack of recruiter equipoise and difficulties communicating with patients about the study, and phase II comprised the development and delivery of tailored strategies to optimise recruitment, including group training, individual feedback and ‘tips’ documents. At the time of data extraction, on 10 October 2017, treatment data were available for 71 patients. Patient characteristics were similar at baseline and the rate of return of all clinical case report forms (CRFs) was 95%; the return rate of the patient-reported outcome measures (PROMs) questionnaire pack was 90.5%. Centres with specific long-standing expertise in offering HIFU as a routine NHS treatment option had lower recruitment rates (Basingstoke and Southampton) – with University College Hospital failing to enrol any participants – than centres offering HIFU in the trial context only.
Conclusions
Randomisation of men to a RCT comparing PA with radical treatments of the prostate is feasible. The QRI provided insights into the complexities of recruiting to this surgical trial and has highlighted a number of key lessons that are likely to be important if the study progresses to a main trial. A full RCT comparing clinical effectiveness, cost-effectiveness and quality-of-life outcomes between radical treatments and PA is now warranted.
Future work
Men recruited to the feasibility study will be followed up for 36 months in accordance with the protocol. We will design a full RCT, taking into account the lessons learnt from this study. CRFs will be streamlined, and the length and frequency of PROMs and resource use diaries will be reviewed to reduce the burden on patients and research nurses and to optimise data completeness.
Trial registration
Current Controlled Trials ISRCTN99760303.
Prostate cancer (PCa) is the most common cancer in men in the UK. Patients with intermediate-risk, clinically localised disease are offered radical treatments such as surgery or radiotherapy, which can result in severe side effects. A number of alternative partial ablation (PA) technologies that may reduce treatment burden are available; however the comparative effectiveness of these techniques has never been evaluated in a randomised controlled trial (RCT).
Objectives
To assess the feasibility of a RCT of PA using high-intensity focused ultrasound (HIFU) versus radical prostatectomy (RP) for intermediate-risk PCa and to test and optimise methods of data capture.
Design
We carried out a prospective, multicentre, open-label feasibility study to inform the design and conduct of a future RCT, involving a QuinteT Recruitment Intervention (QRI) to understand barriers to participation.
Setting
Five NHS hospitals in England.
Participants
Men with unilateral, intermediate-risk, clinically localised PCa.
Interventions
Radical prostatectomy compared with HIFU.
Primary outcome measure
The randomisation of 80 men.
Secondary outcome measures
Findings of the QRI and assessment of data capture methods.
Results
Eighty-seven patients consented to participate by 31 March 2017 and 82 men were randomised by 4 May 2017 (41 men to the RP arm and 41 to the HIFU arm). The QRI was conducted in two iterative phases: phase I identified a number of barriers to recruitment, including organisational challenges, lack of recruiter equipoise and difficulties communicating with patients about the study, and phase II comprised the development and delivery of tailored strategies to optimise recruitment, including group training, individual feedback and ‘tips’ documents. At the time of data extraction, on 10 October 2017, treatment data were available for 71 patients. Patient characteristics were similar at baseline and the rate of return of all clinical case report forms (CRFs) was 95%; the return rate of the patient-reported outcome measures (PROMs) questionnaire pack was 90.5%. Centres with specific long-standing expertise in offering HIFU as a routine NHS treatment option had lower recruitment rates (Basingstoke and Southampton) – with University College Hospital failing to enrol any participants – than centres offering HIFU in the trial context only.
Conclusions
Randomisation of men to a RCT comparing PA with radical treatments of the prostate is feasible. The QRI provided insights into the complexities of recruiting to this surgical trial and has highlighted a number of key lessons that are likely to be important if the study progresses to a main trial. A full RCT comparing clinical effectiveness, cost-effectiveness and quality-of-life outcomes between radical treatments and PA is now warranted.
Future work
Men recruited to the feasibility study will be followed up for 36 months in accordance with the protocol. We will design a full RCT, taking into account the lessons learnt from this study. CRFs will be streamlined, and the length and frequency of PROMs and resource use diaries will be reviewed to reduce the burden on patients and research nurses and to optimise data completeness.
Trial registration
Current Controlled Trials ISRCTN99760303.
Date Issued
2018-09-01
Date Acceptance
2017-11-01
Citation
Health Technology Assessment, 2018, 22 (52)
ISSN
1366-5278
Publisher
NIHR Journals Library
Journal / Book Title
Health Technology Assessment
Volume
22
Issue
52
Copyright Statement
© Queen’s Printer and Controller of HMSO 2018. This work was produced by Hamdy et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that
suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.
suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.
Sponsor
Wellcome Trust
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000446127000001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
204998/Z/16/Z
Subjects
Science & Technology
Life Sciences & Biomedicine
Health Care Sciences & Services
INTENSITY-FOCUSED ULTRASOUND
TARGETED PHOTODYNAMIC THERAPY
RANDOMIZED CONTROLLED-TRIALS
QUALITY-OF-LIFE
INTERSTITIAL TUMOR ABLATION
EXTERNAL-BEAM RADIOTHERAPY
ISUP CONSENSUS CONFERENCE
IRREVERSIBLE ELECTROPORATION
ACTIVE SURVEILLANCE
RADIATION-THERAPY
Publication Status
Published