Tag Archive for: protect trial


April Editorial: The BJUI’s clinical trials initiative

The BJUI supports clinical trials. Plain, simple, and with some new strategies.

Randomised clinical trials (RCTs) are the highest level of evidence-based medicine. We know this to be true, but we also know that RCTs are a challenge to fund, accrue patients, execute, and follow to endpoints. From a statistician’s point of view, RCTs provide unbiased estimates of the effects of different treatments. From a clinician’s point of view, RCTs provide the grandest of experiments in nature – a true test of option A vs option B. We are thrilled when one option beats the other. We can be satisfied if the options are equivalent, at least knowing the matter is settled and move on to the next question. Either way, the story lines can be rich with ongoing debate, drama, and analysis: were the cohorts truly equivalent? Was the study population generalisable? Were the treatments contemporary? Were there unintended harms/toxicities?

Allow us to illustrate some examples of what we propose to our readers. In 2003, Thompson et al. [1] published the famous Prostate Cancer Prevention Trial in the New England Journal of Medicine: ‘The influence of finasteride on the development of prostate cancer’. This landmark study has been cited 2541 times, according to Google Scholar. Looking further at impact, one can go to the www.swog.org site and query the protocol ‘SWOG-9217’ and see that over 150 publications have been produced using this dataset (16 in 2016!). Several publications pre-dated the primary endpoint paper and discussed trial design, the dilemma of chemoprevention, and updates to trial progress. Post primary endpoint, publications have looked at multiple strategies – costs, the high-grade findings, longer-term follow-up, biopsy findings from the placebo arm, etc. Just last year, the UK made its mark on the prostate cancer world with the landmark Prostate Testing for Cancer and Treatment (ProtecT) study [2]. Again, we see the primary endpoint paper in the New England Journal of Medicine, but secondary endpoint papers, such as the quality-of-life outcomes are in the BJUI [3], and a mortality outcome analysis for trial screen failures in European Urology [4].

The BJUI can support clinical trial efforts through multiple pathways. Certainly, we would love to receive a primary endpoint paper from an important RCT in urology. We can also have impact by featuring important secondary endpoint papers, trial design papers (preferably ones that read like a good review article, with the trial proposed as the ‘answer’ to the dilemma), as well as smaller/early phase I–II trials that are stand-alone pieces of key knowledge. Figure 1 shows a possible flow chart of a RCT with each box representing possible publication points. In addition to content in the BJUI, our webpage Blogs section has a ‘rapid response team’ to start immediate dialogue on important RCTs published in other journals. For example with the recent Yaxley et al. [5] trial in the Lancet, our blogs section, led by Declan Murphy, had over 10 000 views and over 50 follow-up comments. So clearly, our readers care about RCTs.


Figure 1. A possible flow chart of a randomised clinical trial (RCT) with each box representing possible publication points. QOL, quality of life; f/u, follow-up.

Finally, the BJUI can help with RCTs in two more ways. For the reader, we will highlight RCT-related papers in their native sections (i.e. oncology, functional, education) with a special ‘Trials’ headline, and will invite experts to comment on the significance of the study. For reviewers and authors, we will be critical on RCT design, such that flaws are identified, and papers not given inflated significance. It is frustrating to receive papers that lack adequate reporting on what researchers did, RCT-related papers submitted to the BJUI frequently fail to adhere to the 2010 Consolidated Standards of Reporting Trials (CONSORT) guidance for reporting RCTs, which potentially leads to major revisions, if not outright rejection. The CONSORT requirements are on our author submission guidelines, but ideally these are read and adhered to in advance, as many are not possible to correct after the fact. Recently, we have also added that all RCTs must be registered (i.e. clinicaltrials.gov or similar) before the first patient is enrolled.

John W. Davis, Associate Editor, Urological Oncology* and
Graeme MacLennan, Consulting Editor, Statistics and Trials

*MD Anderson Cancer Center, Houston, TX, USA and University of Aberdeen, Aberdeen, UK


How to Cite this article

Davis, J. W. and MacLennan, G. (2017), The BJUI‘s clinical trials initiative. BJU International, 119: 503. doi: 10.1111/bju.13837


Article of the Month: PROMs in the ProtecT trial of PCa treatments

Every Month the Editor-in-Chief selects an Article of the Month from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video discussing the paper.

If you only have time to read one article this week, it should be this one.

Patient-reported outcomes in the ProtecT randomized trial of clinically localized prostate cancer treatments: study design, and baseline urinary, bowel and sexual function and quality of life

Athene Lane*,, Chris Metcalfe*,, Grace J. Young*,, Tim J. Peters,§, Jane Blazeby*Kerry N. L. Avery*, Daniel Dedman, Liz Down*, Malcolm D. Mason**, David E. Neal††Freddie C. Hamdy†† and Jenny L. Donovan*,§ for the ProtecT Study group


*School of Social and Community Medicine, University of Bristol, Bristol, Bristol Randomised Trials Collaboration, University of Bristol, Bristol, School of Clinical Sciences, University of Bristol, Bristol, §Collaboration for Leadership in Applied Health Research and Care West, United Hospitals Bristol, Bristol, Clinical Practice Research Datalink Group, Medicines and Healthcare Products Regulatory Agency, London, **School of Medicine, Cardiff University, Cardiff, and ††Nufeld Department of Surgery, University of Oxford, Oxford, UK


To present the baseline patient-reported outcome measures (PROMs) in the Prostate Testing for Cancer and Treatment (ProtecT) randomized trial comparing active monitoring, radical prostatectomy and external-beam conformal radiotherapy for localized prostate cancer and to compare results with other populations.

Materials and Methods

A total of 1643 randomized men, aged 50–69 years and diagnosed with clinically localized disease identified by prostate-specific antigen (PSA) testing, in nine UK cities in the period 1999–2009 were included. Validated PROMs for disease-specific (urinary, bowel and sexual function) and condition-specific impact on quality of life (Expanded Prostate Index Composite [EPIC], 2005 onwards; International Consultation on Incontinence Questionnaire-Urinary Incontinence [ICIQ-UI], 2001 onwards; the International Continence Society short-form male survey [ICSmaleSF]; anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), generic mental and physical health (12-item short-form health survey [SF-12]; EuroQol quality-of-life survey, the EQ-5D-3L) were assessed at prostate biopsy clinics before randomization. Descriptive statistics are presented by treatment allocation and by men’s age at biopsy and PSA testing time points for selected measures.



A total of 1438 participants completed biopsy questionnaires (88%) and 77–88% of these were analysed for individual PROMs. Fewer than 1% of participants were using pads daily (5/754). Storage lower urinary tract symptoms were frequent (e.g. nocturia 22%, 312/1423). Bowel symptoms were rare, except for loose stools (16%, 118/754). One third of participants reported erectile dysfunction (241/735) and for 16% (118/731) this was a moderate or large problem. Depression was infrequent (80/1399, 6%) but 20% of participants (278/1403) reported anxiety. Sexual function and bother were markedly worse in older men (65–70 years), whilst urinary bother and physical health were somewhat worse than in younger men (49–54 years, all P < 0.001). Bowel health, urinary function and depression were unaltered by age, whilst mental health and anxiety were better in older men (P < 0.001). Only minor differences existed in mental or physical health, anxiety and depression between PSA testing and biopsy assessments.


The ProtecT trial baseline PROMs response rates were high. Symptom frequencies and generic quality of life were similar to those observed in populations screened for prostate cancer and control subjects without cancer.

Editorial: ‘Killing Two Birds With One Stone’ – PROMS from the ProtecT Trial

Very few areas of medicine generate more controversy than the management of clinically localised prostate cancer. This is in large part due to the somewhat conflicting nature of the scant level I evidence that exists on the subject. Whereas the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) demonstrated a clinically meaningful and durable survival advantage for surgery when compared to watchful waiting in a predominantly White Scandinavian population of patients with clinically palpable yet localised prostate cancer [1], the Radical Prostatectomy Versus Observation for Localized Prostate Cancer (PIVOT) trial reported a mostly null effect of surgery in a predominantly older, less healthy population of American patients with clinically indolent disease [2]. Neither trial addresses the effect of radiotherapy on prostate cancer survival and both may lack relevance in contemporary prostate cancer practice.

For these reasons and a myriad of others, the medical community eagerly awaits the results of the Prostate Testing for Cancer and Treatment (ProtecT) trial [3]. With a fastidiously designed protocol that involves 337 primary care centres across nine cities in the UK, the use of dedicated study nurses, the successful enrolment of pre-specified sample size targets, and the inclusion of patient-reported quality-of-life measures, the ProtecT trial is poised to make enormous inroads for men with prostate cancer and the providers who care for them.

In this issue of the BJUI, the investigators from the ProtecT trial publish baseline patient-reported outcome measures (PROMs) from the ProtecT trial [4]. While others have previously reported baseline PROMs in large comparative effectiveness studies [5], the findings from this study are notable for several reasons. First, this is the first randomised trial comparing the effect of surgery, radiation, and active monitoring on PROMs. While several high-quality prospective observational cohort studies have reported long-term quality-of-life outcomes after prostate cancer treatment [6, 7], ProtecT will offer randomised comparisons that minimise confounding and selection bias from the outset. Second, the ProtecT trial will not only measure disease-specific health-related quality of life through the use of psychometrically validated survey instruments, such as the Expanded Prostate Index Composite, but also general health-related quality of life through the use of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C-30 (as well as depression and anxiety through the use of the Hospital Anxiety and Depression Scale). Finally, and perhaps most importantly, the investigators collected baseline PROMs at the time of the first biopsy before cancer diagnosis, which will offer distinct advantages when modelling patient-reported function over time, as well as avoiding recall bias associated with retrospective collection of baseline patient-reported outcomes.

In the absence of the long-term survival data from randomised trials comparing surgery and radiation, previous studies have rightly focused on understanding how the effect of prostate cancer treatments differ with respect to PROMs. With the ProtecT trial, we will not only start to have answers to longstanding questions about how surgery, radiation and active surveillance compare with respect to clinical outcomes, such as survival and cancer control, but also with respect to PROMs. By addressing both of these domains, the ProtecT investigators are in position to ‘kill two birds with one stone’ and in so doing will undoubtedly make large strides in facilitating data-driven decision-making for patients with prostate cancer worldwide.

Mark D. Tyson* and David F. Penson*,,


Departments of *Urologic Surgery and Health Policy, Vanderbilt University Medical Center, and‡ Geriatric, Research, and Educational Center, Veterans Affairs Tennessee Valley Health Care System, Nashville, TN, USA




1 Bill-Axelson A, Holmberg L, Garmo H et al. Radical prostatectomy or watchful waiting in early prostate cancer. N Engl J Med 2014; 370: 93242


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