A Proof of Concept Study Evaluating the Role of Emerging Ultrasound Technologies in the Assessment and Monitoring of Localised Prostate Cancer in Men on an Active Surveillance Programme
Phase: NA
Conditions: Prostate Cancer
Sponsor: Hull University Teaching Hospitals NHS Trust

 
 
 
 
Hull University Teaching Hospitals NHS Trust
Unique Protocol ID:HullUTH
A Proof of Concept Study Evaluating the Role of Emerging 
Ultrasound Technologies in the Assessment and Monitoring 
of Localised Prostate Cancer in Men on an Active 
Surveillance Programme 
Study Protocol: Evaluating the Role of Ultrasound in 
Prostate Cancer (ERUP)  
 
6th December 2021 

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Evaluating the Role of Ultrasound in Prostate Cancer Study (ERUP Study) 
 
Full title of the research: 
A proof of concept study evaluating the role of emerging ultrasound technologies in the 
assessment and monitoring of localised prostate cancer in men on an active surveillance 
programme. 
Short title for this project: 
Evaluating the role of ultrasound in prostate cancer 
Lead researcher 
 
 
 
 
 
 
 
 
Pamela Parker 
Consultant Sonographer 
Ultrasound, Hull Teaching Hospitals 
 
Research team 
 
 
 
Mr Matthew Simms 
Consultant Urologist 
Urology, Hull Teaching Hospitals 
Dr Maureen Twiddy 
 
Dr Paul Whybrow 
 
Professor Alan Rigby 
 
 
 
 

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Abstract 
Research plan, study design and protocol 
Summary of the study: 
Active surveillance (AS) is becoming an increasingly common treatment option for men who 
have been diagnosed with localised low-grade prostate cancer (PCa). Low-grade disease is 
commonly noted by clinicians to be clinically insignificant cancer but remains a psychological 
burden to many men in this cohort. There is consensus that regular review is required for men 
on AS so that early treatment can be undertaken if there is disease progression, and to support 
men living with a cancer diagnosis. Some AS protocols, including NICE, advocate the use of MRI 
as a regular part of the monitoring pathway. Unfortunately, access to MRI for AS, within the 
current health care environment in the UK, is limited due to increasing demand for primary 
diagnostic examinations, particularly in the post Covid-19 recovery phase. Emerging 
technologies in ultrasound imaging may, however, add another diagnostic tool to monitor 
disease for patients on AS. This proof of concept study is to evaluate whether new multi-
parametric ultrasound techniques can safely reduce the number of MRIs required for effective 
AS. 
Men being investigated for PCa will be invited to undergo an ultrasound examination of their 
prostate, via the rectum, in addition to the diagnostic MRI undertaken as part of normal care. 
The findings of the ultrasound will be directly compared with the MRI and any subsequent 
biopsy samples taken as part of routine care. Those who then progress onto AS will be invited 
to undergo regular rectal prostate ultrasound examinations. These will be compared with 
previous imaging for signs of change. 
This study will also evaluate the changing role of practitioners who will be using new 
technologies and making decisions about disease progression. The ability to implement new 
techniques will be assessed. All imaging will be undertaken at Castle Hill Hospital over a 24-
month period from commencement of the study. 
 
 

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Contents 
Evaluating the Role of Ultrasound in Prostate Cancer Study (ERUP Study) ............................... i 
Full title of the research: ............................................................................................................. i 
Short title for this project: .......................................................................................................... i 
Lead researcher........................................................................................................................... i 
Research team ............................................................................................................................ i 
Abstract ...................................................................................................................................... ii 
Research plan, study design and protocol ................................................................................... ii 
Summary of the study: ............................................................................................................ ii 
Research Plan ................................................................................................................................ 6 
1.1 
Purpose and design ....................................................................................................... 6 
1.1.1 
Clinical context: ..................................................................................................... 6 
1.1.2 
Technological improvements ................................................................................ 7 
1.1.3 
Implementing change ........................................................................................... 7 
1.1.4 
Skill mix ................................................................................................................. 8 
1.1.5 
Normalisation Process Theory (NPT) .................................................................... 8 
1.2 
Study Aim ...................................................................................................................... 8 
1.3 
Primary and secondary objectives ................................................................................ 9 
1.3.1 
Primary objective .................................................................................................. 9 
1.3.2 
Secondary objectives ............................................................................................ 9 
1.4 
Study phases ................................................................................................................. 9 
1.4.1 
Phase 1: ................................................................................................................. 9 
1.4.2 
Phase 2: ............................................................................................................... 10 
1.4.3 
Phase 3: ............................................................................................................... 10 
1.4.4 
Phase 4: ............................................................................................................... 10 
1.5 
Study design and methodology – Phase 1 .................................................................. 11 
1.5.1 
Phase 1: Patient population ................................................................................ 11 
1.5.2 
Eligibility criteria in clinical practice .................................................................... 11 
1.5.3 
Phase 1 recruitment ............................................................................................ 11 
1.5.4 
Sample size – phase 1 ......................................................................................... 11 
1.5.5 
Inclusion criteria for phase 1 ............................................................................... 12 
1.5.6 
Exclusion criteria for phase 1 .............................................................................. 12 
1.5.7 
Phase 1 recruitment process .............................................................................. 13 

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1.5.8 
Ultrasound appointments – phase 1................................................................... 13 
1.5.9 
Image collection .................................................................................................. 13 
1.5.10 
Scan protocol ...................................................................................................... 13 
1.5.11 
Data collection - Phase 1 ..................................................................................... 15 
1.5.12 
Data assessment ................................................................................................. 15 
1.5.13 
Data collation ...................................................................................................... 15 
1.5.14 
Data analysis ....................................................................................................... 16 
1.6 
Study design and methodology – Phase 2 .................................................................. 16 
1.6.1 
Phase 2 recruitment ............................................................................................ 16 
1.6.2 
Sample size phase 2 ............................................................................................ 17 
1.6.3 
Inclusion criteria for phase 2 ............................................................................... 17 
1.6.4 
Exclusion criteria for phase 2 .............................................................................. 17 
1.6.5 
Phase 2 recruitment process .............................................................................. 18 
1.6.6 
Participation and patient contact ....................................................................... 18 
1.6.7 
Image collection Phase 2..................................................................................... 18 
1.6.8 
Data collection phase 2 ....................................................................................... 18 
1.6.9 
Data assessment phase 2 .................................................................................... 19 
1.6.10 
Data analysis phase 2 .......................................................................................... 19 
1.7 
Phase 3: Staff population ............................................................................................ 19 
1.7.1 
Cohort ................................................................................................................. 19 
1.7.2 
Data collection tool ............................................................................................. 19 
1.7.3 
New technology impact assessment ................................................................... 20 
1.7.4 
Phase 3 sample ................................................................................................... 20 
1.7.5 
Conflicts of interest ............................................................................................. 20 
1.7.6 
Lead researcher considerations .......................................................................... 21 
1.7.7 
Inclusion criteria for phase 3 ............................................................................... 21 
1.7.8 
Exclusion criteria for phase 3 .............................................................................. 21 
1.7.9 
Phase 3 data collection ....................................................................................... 21 
1.7.10 
Phase 3 participant and data confidentiality ...................................................... 22 
1.7.11 
Data analysis ....................................................................................................... 22 
1.8 
Phase 4 ........................................................................................................................ 22 
1.8.1 
Inclusion criteria for phase 4 ............................................................................... 22 
1.8.2 
Exclusion criteria for phase 4 .............................................................................. 22 
1.9 
Consent ....................................................................................................................... 23 
1.9.1 
Phase 1 consent .................................................................................................. 23 
1.9.2 
Phase 2 consent .................................................................................................. 23 

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1.9.3 
Phase 3 consent .................................................................................................. 23 
1.10 
Risks, burdens and benefits ........................................................................................ 24 
1.10.1 
Phase 1 ................................................................................................................ 24 
1.10.2 
Phase 2 ................................................................................................................ 25 
1.10.3 
Phase 3 ................................................................................................................ 25 
1.10.4 
Phase 4 ................................................................................................................ 26 
1.11 
Confidentiality ............................................................................................................. 27 
1.12 
Approval ...................................................................................................................... 27 
1.13 
Data security ............................................................................................................... 27 
1.13.1 
Incidental or adverse clinical findings ................................................................. 27 
1.14 
Conflict of interest ...................................................................................................... 28 
1.15 
Use of tissue samples in future research .................................................................... 28 
1.16 
Appendix 1: Evaluating the role of diagnostic ultrasound in prostate cancer – Current 
clinical pathway. Referral to diagnosis ................................................................................... 29 
1.17 
Appendix 2: Evaluating the role of diagnostic ultrasound in prostate cancer – Phase 1 
recruitment ............................................................................................................................. 30 
1.18 
Appendix 3: Evaluating the role of diagnostic ultrasound in prostate cancer – Phase 2 
recruitment ............................................................................................................................. 31 
1.19 
Appendix 4: Ultrasound in prostate cancer – Phase 1 Image review pathway .......... 32 
1.20 
Appendix 5: Diagnostic ultrasound in prostate cancer – Phase 2 Image review 
pathway .................................................................................................................................. 33 
1.21 
Appendix 6: Data collection form – Standard Ultrasound .......................................... 34 
1.22 
Appendix 7 – Data collection form – Micro-ultrasound ............................................. 35 
1.23 
Appendix 8 – Phase 3 Implementation Survey ........................................................... 36 
References .............................................................................................................................. 37 
 
 

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Research Plan 
1.1 Purpose and design 
Across the UK prostate cancer is the most common cancer in men. Developments in magnetic 
resonance imaging (MRI), and the implementation of a targeted biopsy regime, have resulted in a 
considerable improvement in the detection of prostate cancer. The advent of robotic prostatectomy, 
and improvements in radiotherapy, have both lessened the post-treatment side effects but no 
treatment is without significant risk of complications.  
1.1.1 Clinical context: 
Prostate cancer can be present as an indolent low-grade cellular change to the tissue but with very 
little risk of this progressing to a metastatic life threatening disease. Despite the improved diagnostic 
capabilities, there remain a significant proportion of men in whom low-grade cancer is detected and 
consequent treatment options may present a higher risk to quality of life than the presence of the 
localised disease. NICE CG 131 (2019) recommends men are offered active surveillance (AS) or 
watchful waiting (WW) as an option for low-risk localised prostate cancer and for whom radical 
prostatectomy or radical radiotherapy is suitable should advancing disease be detected. Both AS and 
WW involve proactively monitoring the patient for signs of disease progression rather than 
undertaking treatment immediately. Patients on an AS pathway are deemed suitable for 
intervention and curative treatment should there be signs of disease progression; patients on a WW 
pathway usually have comorbidities that preclude curative treatment but they may benefit from 
palliative care if there is evidence of future progression.  The Prostate Testing for Cancer and 
Treatment (ProtecT) (Hamdy et al. 2016) trial was established to gain a better understanding of the 
effectiveness of treatments, including AS, for prostate cancer. ProtecT  (Hamdy et al. 2016) 
concluded that, at a median of 10 years, prostate cancer specific mortality was low regardless of the 
treatment assigned and that adopting an AS approach is reasonable to avoid life limiting side effects 
(Da Silva et al. 2017, Klotz et al. 2015). 
However, despite the findings of the ProtecT trial (Hamdy et al. 2016) and the NICE guidance  131 
(NICE 2019) there is currently no standard approach to AS due to the inequalities in capacity and 
availability of services in the NHS.  It is, however, agreed that men on AS require regular tests which 
should include a combination of the following: 
 
Prostate Specific Antigen (PSA) 
 
digital rectal examinations (DRE) 

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 
MRI scans  
 
prostate biopsies – either transrectal random or transperineal template biopsy 
The improvements in MRI imaging and reporting indicate that regular scans would add valuable 
information for patients under AS but capacity is significantly hindering this as an available 
application. An overview of the current clinical pathway for patients in the local region is provided as 
appendix 1. This highlights the very real impact that capacity issues in MRI has on patient diagnostic 
pathways. 
1.1.2 Technological improvements 
However, emerging technologies in ultrasound imaging, which is less hindered by capacity issues 
within the UK and is utilised, to a degree, in current standard care, may add another diagnostic tool 
to monitor disease for patients on AS. A multi-parametric ultrasound assessment may provide the 
crucial diagnostic features that enables ultrasound imaging to be used to monitor disease. A multi-
parametric assessment will include standard frequency ultrasound, Doppler ultrasound and high 
frequency ultrasound imaging. High frequency ultrasound (micro-US) increases the detail of 
structures imaged, compared to standard trans-rectal ultrasound, and has been demonstrated to be 
a promising new modality for targeted prostate assessment compared to MRI (Maffei et al. 2019). A 
recent paper by Matheson et al. (2019) has demonstrated that most men on AS cope well 
psychologically but the paper is limited in its exploration of what alternative intervention could be 
made to improve well-being within a AS programme. A crucial question remains as to whether the 
use of additional imaging and health care intervention could improve patient outcomes. 
1.1.3 Implementing change 
Traditionally, radiologists or urologists have performed the diagnostic transrectal prostate biopsy 
procedures within the cancer pathway. In more recent years, skill mix has developed and there is an 
increasing number of sonographers undertaking these examinations enabling medical capacity to be 
released. Within the Hull University Teaching Hospitals NHS Trust, the vast majority of prostate 
biopsies are undertaken by sonographers. Sonographers are trained and qualified to interpret 
ultrasound imaging. They provide diagnostic reports as part of routine practice. The limitations of 
traditional US technology used to guide transrectal prostate biopsy precluded any diagnostic 
assessment during the biopsy procedures; US is used purely to guide where samples will be taken.  
 

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1.1.4 Skill mix 
The advent of multi-parametric ultrasound may enable a diagnostic assessment of the prostate, both 
at the initial biopsy and during AS. This will be an additional skill the sonographer will be required to 
develop. The benefits of skill mix have been documented by various authors, most recently Field and 
Snaith (2013). However, the impact of role development on sonographers and their radiologist 
colleagues, which includes changes to roles, responsibilities and accountabilities, has not been 
previously investigated in any depth. A workforce review by Parker and Harrison (2015) identified 
that appropriate training in ultrasound is key to providing a safe diagnostic and interventional 
ultrasound service but what constitutes appropriate training is less well defined.  
 
1.1.5 Normalisation Process Theory (NPT) 
Despite the publication of a defined framework for the development and evaluation of research, 
there remain substantial problems in the design and conduct of studies introducing complex 
interventions and their subsequent implementation (Finch et al. 2018). The understanding of an 
implementation processes is key to ensuring that proposed changes to techniques, technologies or 
interventions are both implemented and sustained in practice; desired outcomes of a ‘successful’ 
implementation do include the experiences of those providing the service. If a new technology 
provides good diagnostic results but is cumbersome and complex to use, it is unlikely to be 
implemented into routine healthcare practice. A recognised gap exists between developing new 
treatments and knowledge, and implementing these in practice for the patient who may benefit (De 
Brún et al. 2016, May, Johnson and Finch 2016). An understanding of the ability to implement the 
proposed new complex ultrasound techniques in real-life clinical practice will be explored within this 
proof of concept study. Normalisation process theory (NPT) is the theoretical approach being utilised 
in this study. NPT is a theory which described the collective work that stakeholders need to engage 
in to implement interventions in the real world of everyday clinical practice. NPT has 4 components 
that practitioners need to adopt in order to embed a new process or technology into routine 
practice. The 4 components: Coherence, Cognitive Participation, Collective Action, and Reflexive 
Monitoring. These will be explored further in the staff focussed third phase of the study.  
1.2 Study Aim 
This aim of this proof of concept study is to evaluate if emerging ultrasound technologies can 
provide reliable and reproducible imaging that can be used to assess the prostate gland in men with 
known localised prostate cancer and who are being managed with active surveillance. 

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The impact of additional skill mix for health care practitioners within diagnostic imaging, in the field 
of prostate cancer assessment and monitoring, will be investigated as a secondary objective of this 
study. As with many research studies, data is collected in a strict and controlled environment which 
may not readily translate into a real life clinical setting. The feasibility for implementing changes to 
the imaging pathways in active surveillance will also be evaluated with the clinical team delivering 
the current and future service.  
1.3 Primary and secondary objectives 
1.3.1 Primary objective 
The primary objective of the study is to evaluate if emerging multi-parametric ultrasound 
technologies can provide a viable tool to be used in the active surveillance of men with known 
localised prostate cancer. 
1.3.2 Secondary objectives 
Secondary objectives of this study are: 
 
to evaluate the diagnostic parameters of diagnostic ultrasound that can be utilised to assess 
disease within the prostate gland. 
 
To evaluate the diagnostic parameters of diagnostic ultrasound that can be utilised to assess 
disease progression within the prostate gland. 
 
To evaluate if the intra and inter operator variability in the assessment of ultrasound 
imaging parameters of the prostate gland can be investigated. 
 
To determine if a suitable standardise imaging protocol and reporting tool or model could be 
utilised in the reporting of transrectal ultrasound imaging of the prostate. 
 
To gain a better understanding of how new ultrasound technology and techniques can be 
implemented and embedded into clinical practice. 
1.4 Study phases 
This study is being undertaken as a PhD research project but within the NHS care setting. The study 
will consist of four phases: 
1.4.1 Phase 1:  
In this initial phase, eligible men who have consented to participate will undergo a transrectal 
ultrasound examination with a standard ultrasound probe and, at the same attendance a transrectal 
ultrasound examination with a new and novel probe using 29MHz scanning frequency. The images 
obtained from this examination will be retrospectively compared with the MRI imaging that has 
been obtained as part of the standard care pathway. The images obtained will be reviewed by two 

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health care practitioners with experience in prostate imaging and the outcomes of these reviews 
compared to evaluate agreement levels. 
1.4.2 Phase 2: 
The second phase of the study will evaluate the use of multiparametric standard and micro 
ultrasound in the assessment of men who are on an AS or WW pathway. This phase the study will 
evaluate if there are any changes in the findings at repeat ultrasound examinations that can indicate 
disease progression. Eligible men, who have consented to participate, will again undergo a 
transrectal ultrasound examination with a standard ultrasound probe and, at the same attendance a 
transrectal ultrasound examination with a new and novel probe using 29MHz scanning frequency.  
1.4.3 Phase 3:  
The process and acceptability of implementing new interventions and technologies into everyday 
clinical practice is frequently overlooked following research trials. This third phase will explore the 
views of the health care practitioners, who have consented to participate, regarding the use and 
implementation of the proposed new technologies; skill mix between these professional groups will 
be required for successful long term practice. The participants will be recruited from differing 
professionals within the staff groups of Hull University Teaching Hospitals NHS Trust. An adapted 
survey tool, derived from normalisation process theory framework, will be used to better 
understand how and if the new, complex, multi-parametric ultrasound techniques can be 
implementation within the organisational setting of everyday routine practice.  A baseline 
assessment of confidence in knowledge and skills related to prostate cancer evaluation using 
ultrasound will be made.  
1.4.3.1 
Staff training: 
Participants in phase 3 will then be provided with training using specific multi-parametric US 
techniques and will regularly score multi-parametric US examinations. Participants’ confidence in 
knowledge and skills, related to prostate cancer evaluation using US, and how they feel this can be 
implemented into regular patient care will be assessed, using the same adapted survey at baseline at 
6 - 12 months’ post implementation. 
1.4.4 Phase 4:  
A fourth phase of the study is planned. Once outcomes from the initial 3 phases of the study are 
known the lead researcher intends to organise a national meeting where results will be presented 
and discussion held between the research team and other centres providing a diagnostic prostate 
cancer service. The aim of this event is to disseminate results and to obtain a wider understanding of 

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its acceptance beyond local practice. Multi-parametric ultrasound is novel and there may be 
resistance to wider implementation. Opportunities and barriers will be explored at this phase 4 
event.  
The study phases will run concurrently and will be managed by the lead researcher.  
1.5 Study design and methodology – Phase 1 
1.5.1 Phase 1: Patient population 
With consent, all eligible men will be invited to participate in the first phase of the study; appendix 1 
outlies the current care pathway and the eligibility criteria utilised in this study.  Multi-parametric US 
will be used to assess the prostate gland prior to the ultrasound guided diagnostic prostate biopsies 
which is performed as part of routine care. The multi-parametric US examination will be performed 
blinded to the pre-biopsy MRI undertaken as part of routine care. Multi-parametric US findings will 
be scored and subsequently correlated to MRI and any related histology findings which are recorded 
as part of routine care. 
1.5.2 Eligibility criteria in clinical practice 
MRI is offered to all men who meet the eligibility criteria of age ≤75, PSA ≤ 20 and life expectancy of 
≥ 10 years. MRI is reported using the PI-RADS V2 criteria; a 5 point scale with 1 & 2 highly unlikely to 
have significant prostate cancer, 4 & 5 highly likely to have significant prostate cancer and PI-RADS 3 
equivocal and further investigation warranted. The pathway in the Hull University Teaching Hospitals 
NHS Trust is that patients with PI-RADS score of 1 or 2 are not routinely offered biopsy due to the 
risk of biopsy complications being greater than the likelihood of prostate cancer. Men meeting these 
criteria will be invited to participate in phase 1 of the study and the multi-parametric US will be 
correlated with MRI only. A biopsy will not be performed. Any men from this cohort electing for AS 
will be invited to join phase 2. 
1.5.3 Phase 1 recruitment 
Participants for phase 1 of the study will be invited from the cohort of patients referred into Hull 
Teaching Hospitals with suspected prostate cancer and who meet the criteria for pre prostate biopsy 
MRI. Appendix 1 outlines the current clinical pathway and participants for the study will be invited 
from those who fulfil the criteria for pathway A of the local service.  
1.5.4 Sample size – phase 1 
As this is a proof of concept study testing the technology of ultrasound and with no previous 
comparable data little is known about the standard deviation and the distribution of US scores. This 

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makes determining a sample size based on means and variances difficult. Therefore, a sample size 
estimation is based on a representative proportional of the annual referral rate into this service. The 
sample size for phase 1 will be a minimum of 30 patients and a maximum of 60 patients. This 
represents 5% - 10% of the total patient population presenting with suspected prostate cancer and 
undergoing prostate biopsy in one calendar year.  Given the small numbers within this cohort, all 
eligible participants will be invited to continue onto phase 2 of the study with maximum cohort of 30 
being accepted.  
1.5.5 Inclusion criteria for phase 1 
The recruitment criteria and pathway for the clinical phases of the study are outlined in the flow 
charts, appendix 1 and appendix 2. These identify when the participants will be invited to 
participate, when consent will be obtained and the broad outline of the involvement in the study 
that participants can expect. 
Men referred to urology within Hull University Teaching Hospitals NHS Trust with suspected, but 
undiagnosed, prostate cancer and: 
 
Are aged equal to 75 or less 
 
PSA equal to 20 or less 
 
Have had a clinical assessment and deemed to have a life expectancy of 10 years or more 
 
Are able to tolerate a rectal ultrasound examination 
 
Able to provide informed consent to the study 
 
Have had  a multi-parametric MRI performed as part of routine care pathway 
 
MRI results will not preclude invitation for participation; men with PI-RADS 1 & 2, who would 
not be offered biopsy under routine care, are also included in the study. This phase 1 US 
imaging will be an addition examination for this cohort of patients. Consent for the addition 
imaging is required. Reference is made to the Phase 1 PIS (v2 03.11.21) and phase 1 ICF (v2 
03.11.21). 
1.5.6 Exclusion criteria for phase 1 
 
Patients accessing care in Hull University Teaching Hospitals NHS Trust but who are not 
suspected of having prostate cancer 
 
Men referred to urology but who do not meet the eligible criteria for MRI as part of the 
routine care pathway. This includes men who are over 75 and / or have a PSA over 20 
 
Men who meet eligibility criteria but in whom MRI has not been completed (due to lack of 
compliance, artefact, contraindications etc) 
 
Men who are eligible for inclusion but who cannot tolerate rectal ultrasound examinations. 

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 
Men who are unable to consent to the study 
1.5.7 Phase 1 recruitment process 
Patients are seen in a specific prostate assessment clinic by a urology nurse specialist. A clinical 
history is taken and from there, referrals for both MRI and ultrasound guided prostate biopsy are 
made. At this appointment, all patients will be given an information leaflet for the study. The MRI is 
undertaken within 14 days of referral; the ultrasound guided prostate biopsy can only be performed 
following the MRI. The MRI can be distorted due to post biopsy haemorrhage in the prostate gland, 
and, more importantly, the MRI provides crucial information related to suspected areas of pathology 
in the gland which are targeted during the biopsy procedure. During the time from referral to MRI 
the patient will be contacted by the lead researcher and invited into the ultrasound study.  
1.5.8 Ultrasound appointments – phase 1 
A mutually convenient appointment will be made and confirmed with an appointment letter. The 
phase 1 recruitment pathway is provided in appendix 2. The patient will attend at the agreed date 
and time and a face to face consultation with the lead researcher will be undertaken to discuss the 
study and obtain written consent. The lead researcher will be blinded to the results of the MRI or 
previous studies at this time to minimise undue coercion into the study.  
1.5.9 Image collection  
Once written consent has been obtained, the patient will be shown to a private changing area, 
directly adjacent to the ultrasound examination room and asked to change into a hospital gown. The 
patient will be escorted into the scan room for the procedure to be undertaken. A chaperone will be 
present with consent of the patient, as per standard clinical practice.  A randomly allocated 
sonographer who has consented to participate in the study will be introduced and verbal consent 
obtain for the procedure to commence. 
1.5.10 Scan protocol 
The patient will be positioned in a left sided-decubitus position or lithotomy position depending 
upon which is most comfortable for them. Once comfortable an ultrasound probe from a standard 
ultrasound machine with a scan frequency of 7.5MHz, and about the size of an adult male’s index 
finger, is gently placed into the rectum and the prostate identified. The following images of the 
prostate will be obtained and saved onto the PACS system 
During the ultrasound examination, the prostate gland will be scanned in a longitudinal and 
transverse plane from the apex to base, including seminal vesicles, and from right lateral border to 

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left lateral border. A standard imaging preset will be used and no changes to the scan frequency, or 
pre-processing software are to be made. The scan will be captured and stored as a video loop. 
Systematic still images of the prostate will also be captured and stored. The systematic images 
acquired are: 
1.5.10.1 Longitudinal plane: 
Right lateral 
 
 
Left lateral   
Right mid  
 
 
Left mid  
Central/ Midline 
1.5.10.2 Transverse plane: 
Seminal vesicles 
 
Base 
Mid gland 
 
 
Apex 
The prostate volume will be calculated using the following standard volume formula: height (cm) x 
width (cm) x length (cm) x 0.53 and documented in mL. 
Colour flow Doppler imaging will be applied to evaluate the presence of any perfusion within the 
gland. With colour flow Doppler applied the same set of images will be stored. 
The probe will be removed.  
The examination will then be repeated using high frequency micro-ultrasound technology. Again, a 
standard imaging preset will be used and no changes to the scan frequency, or pre-processing 
software are to be made. This repeat examination will involve a second probe being inserted into 
the rectum, again about the size of a large male adult’s index finger. Imaging of the prostate at 
29MHz will be undertaken. Cine loops of the right and left lobes of the gland will be recorded. Five 
still images of the prostate will be captured at the midline, right mid gland, right lateral gland, left 
mid gland, and left lateral gland. 
The probe will be removed.  Both ultrasound examinations will take no more than a maximum of 10 
minutes to complete ( 5 minutes each scan). Standard infection control procedures will be 
undertaken to clean ultrasound equipment, the examination couch and all peripherals. 
The image collection for the study is complete and the patient will then proceed to undergo 
standard care dependent upon the findings of the MRI. The patient will be met by the sonographer 

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assigned to provide the consultation and biopsy as part of the standard care. Findings of the MRI will 
then be discussed with the patient and the patient’s pathway will proceed as normal. 
1.5.11 Data collection - Phase 1  
Each participant will be given a unique study ID number. All images, cine loops and data for the 
study will be acquired and stored under this separate study ID. The data will be stored on the Hull 
Teaching Hospitals password protected picture archive and reporting system (PACS). A password 
protected database, stored in a password protected network drive of Hull Teaching Hospitals will 
hold the unique identifier number and will be used to record study data. 
The lead researcher will randomly allocate a unique identifier number to two of the participating 
healthcare professionals. The reviewers will be randomly allocated to reduce bias as far as possible 
within a small team. Each reviewer will have their own unique identifier number known only to the 
lead researcher. The identity of the reviewers will be anonymised. The images and cine loops stored 
for the study will have no patient identifiable data on them. Appendix 4 outlines the image 
acquisition and review pathway for phase 1 of the study. 
1.5.12 Data assessment 
The set of images and cine loops will be reviewed, in retrospect, by the assigned reviewers. The 
images and cine loop will be reviewed via a PACS workstation with monitor quality, and viewing 
conditions, as similar as possible to the ultrasound monitors and scan rooms. The save images will be 
scored using a 5-point scale, similar to the established PI-RADSV2 prostate reporting scoring system 
used to report MRI. This 5-point scale provides a score of the ultrasound appearance ranging from 
homogeneous and mid-grey (highly likely to be benign) through to heterogeneous and echo-poor 
(highly likely to be malignant). Any identified focal areas will be measured and the site documented 
dependent upon where in the gland the image was taken. Assessment of the presence of Colour 
flow Doppler will documented on a 3-point scale ranging from no colour Doppler signal evident to 
florid colour Doppler evident (signal fills the imaging sample box).  The scoring system for the 
standard ultrasound and micro ultrasound images is provided in Appendix 6 (standard) and 
Appendix 7 (micro). Once reviewed, the scores submitted on the data collection forms will be 
uploaded onto the database by the lead researcher.  
1.5.13 Data collation 
Once the reviewers scores have been uploaded onto the database, the lead researcher will review 
the clinical information taken as part of the standard care consultation. This will include the PSA 
level and documented DRE report. Both will be added to the database. The MRI report is undertaken 

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16 
as part of the standard care pathway. The MRI PI-RADS score and documented site of abnormality 
will be recorded on the data base. The histology results of any prostate biopsies undertaken will also 
be reviewed and the histological Gleeson score added to the database.  
1.5.14 Data analysis 
Once the database is complete for each participant, the lead researcher will compare the: 
 
ultrasound scores  
 
ultrasound colour Doppler findings 
 
prostate volume size 
 
lesion size 
The above criteria will be compared between both the standard and micro-US imaging, and then the 
standard and micro-US with both MRI and histology. An assessment of agreement will be 
undertaken to evaluate the concordance between the two reviewers of the same images  
(Ranganathan, Pramesh and Aggarwal 2017). The relationship between these pairs will be evaluated 
using Bland-Altman plots. Scores from the ultrasound reviews will also be evaluated to determine 
inter-and intra-operator agreement between the randomly allocated reviewers. The inter-rater 
reliability, both within and across subgroups of reviewers, will be assessed using the intra-class 
correlation coefficient or the Cohen weighted kappa test (de Raadt et al. 2021). 
1.6 Study design and methodology – Phase 2 
Men eligible for AS will be invited to participant in phase 2. A multi-parametric US examination will 
be undertaken as part of the AS monitoring regime. Men under AS have a prostate serum antigen 
(PSA) blood test and digital rectal examination every 6 months. A multi-parametric US examination 
will be undertaken at these appointments to minimise unnecessary health care interactions for the 
participants. The multi-parametric US examination will be performed blinded to the previous 
examinations and histology results. The images will be scored and then correlated with previous 
imaging scores and current PSA levels. Any changes will be indicated to the lead urologist and the 
patients will be offered MRI imaging to evaluate any changes using existing gold standard imaging. 
1.6.1 Phase 2 recruitment  
Participants into phase 2 of the study will be invited from the cohort of patients who have already 
undergone investigations for suspected prostate cancer which include MRI imaging as a requisite. 
Patients who have low probability MRI scores of PI-RADS 1 or 2 will be invited onto the phase 2 
longitudinal arm of the study. Patients who have had biopsy and have either low risk localised 

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prostate cancer and have elected to be monitored with AS, or those with higher grade disease and 
who have elected to be monitored via a WW pathway will also be invited on to the phase 2 
longitudinal arm of the study. 
1.6.2 Sample size phase 2 
Again, determining a sample size for this proof of concept study remains difficult. Given the small 
numbers likely to be recruited into phase 1 and therefore eligible to continue to phase 2, all phase 1 
participants who are managed under AS or WW will be invited to continue onto phase 2 of the study 
with maximum cohort of 30 being accepted. It is acknowledged that inclusion in phase 2 is 
dependent upon cancer grading at diagnosis and, due to uncertainty of disease diagnosis within the 
cohort it may be difficult to recruit participants within the two-year time limit for data collection. 
Participants in phase 1 and 2 will continue to be recruited up to a maximum of 18 months from the 
commencement of the study to maximise the opportunity for phase 2 recruitment. 
1.6.3 Inclusion criteria for phase 2 
Men referred to urology within Hull University Teaching Hospitals NHS Trust with known localised 
prostate cancer of Gleeson 3 + 3 (6) or less and: 
 
Are eligible for an AS monitoring pathway 
 
Are on an AS monitoring pathway which is regularly reviewed by a consultant urologist 
 
Able to attend Castle Hill Hospital for 6 monthly multi-parametric US examinations 
 
Are able to tolerate a rectal ultrasound examination 
 
Able to provide informed consent to the study 
1.6.4 Exclusion criteria for phase 2 
 
Men who meet eligibility criteria for active surveillance but have elected to undergo active 
treatment (hormone treatment, prostatectomy or radiotherapy) 
 
Men who do not meet eligibility criteria for active surveillance 
 
Men who are eligible for inclusion but who cannot tolerate rectal ultrasound examinations. 
 
Men who are unable to consent to the study 
 
Men who withdraw consent during the longitudinal study 
 
Men who are unable to attend Castle Hill Hospital for ultrasound imaging within study time 
frames 

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1.6.5 Phase 2 recruitment process 
Once the initial diagnosis has been made, patients are discussed at the urology prostate multi-
disciplinary meeting. A decision is made as to the most appropriate course of treatment is made and, 
following this, the patients attend for a consultation within a specialist prostate cancer clinic. Biopsy 
results and MDT outcomes are discussed and the patient is given the advised options for 
management. For localised low risk disease this does include active surveillance. For patients who 
may be less eligible for active or even deferred treatment an option of watchful waiting prior to 
palliative treatment being given can be offered. Providing all patients within these cohorts have had 
pre-biopsy MRI they are eligible for the study.  
1.6.6 Participation and patient contact 
Following consultation and treatment choice the eligible patients will be given an information leaflet 
about the study. The lead researcher will be informed of the patients who have been approached by 
the specialist nurse. The lead researcher will then contact the patient by telephone and invite them 
to participate in the study. The phase 2 recruitment pathway is provided in appendix 3. Once verbal 
consent has been given, a mutually convenient appointment will be made and confirmed with an 
appointment letter.  
The patient will attend for agreed appointment and a face to face consultation with the lead 
researcher will be undertaken to discuss the study and obtain written consent. The lead researcher 
will be blinded to the results of the MRI and any previous ultrasound image collection at this time to 
minimise undue coercion into the study, as in phase 1.  
1.6.7 Image collection Phase 2 
The ultrasound examination described and image collection for phase 2 is identical to that of phase 
1. The exception being that once the images have been collected and stored the patient will be free 
to leave; no further consultation, procedure or examination will be undertaken. 
1.6.8 Data collection phase 2  
The data collection of phase 2 is identical to that of phase 1. Data collections forms utilised are 
attached in Appendix 6 & Appendix 7. The current standard and micro-ultrasound collected as part 
of phase 2 will be reviewed by two randomly allocated reviewers and scored as outlined above.  

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1.6.9 Data assessment phase 2 
Once scored the documented criteria will be compared between both the standard and micro-US 
imaging collected during phase 2, and then compared with the previous standard and micro-US 
imaging collected during phase 1.  
1.6.10 Data analysis phase 2 
The relationship between these pairs will be evaluated using Bland-Altman plots as per phase 1. 
Scores from the ultrasound reviews will also be evaluated to determine inter-and intra-operator 
agreement between the randomly allocated reviewers. The phase 1 images and cine loop are the 
baseline data that all subsequent phase 2 examinations undertaken on that particular participant 
will be compared. 
Any changes between the initial ultrasound scores and subsequent scores obtained during the 
longitudinal phase 2 study will be alerted to the lead clinical supervisor (Consultant Urologist) and 
the patient will be reviewed at the next MDT.  
1.7 Phase 3: Staff population 
Phase 3 of the study aims to evaluate staff’s views about how the novel use of multi-parametric and 
micro ultrasound impacts on their work, and their expectations about whether it could become a 
routine part of their clinical practice.  
1.7.1 Cohort 
Phase 3 participants are invited from the staff population. Sonographers and radiologists involved in 
the current prostate cancer pathway will be invited to participate in the study.  
1.7.2 Data collection tool 
Normalization Process Theory (NPT) provides a framework for understanding how a new 
intervention becomes part of normal practice. A survey aligned with NPT will be used to develop an 
understanding of the complexity of the work involved in the implementation of using ultrasound 
within prostate cancer diagnosis and assessment. The survey will be used at the beginning of the 
study and again at between 6 - 12 months’ post commencement to evaluate if perceptions have 
changed over time. NPT will be used to better understand healthcare practitioners feel about the 
implantation of new and complex techniques and technology.  
1.7.2.1 
NPT components 
Qualitative data, collection via the survey from participants in phase 3, will be gathered to better 
understand the following: 

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 
When they use and interpret / score the new technology how familiar does it feel? 
 
Do they feel that the new technology and interpretation is currently a normal part of their 
work? 
 
Do you feel that the new technology and interpretation will become a normal part of their 
work? 
1.7.2.2 
NPT domains 
The survey will investigate the four domains of NPT. It will investigate the ways that participants 
make sense of the work of implementing and integrating multi-parametric and micro ultrasound into 
practice (coherence); how they engage with it (cognitive participation); enact it (collective action); 
and appraise its effects (reflexive monitoring). This phase of the study will evaluate any differences 
between different grades of staff using ultrasound in this study and between professional groups 
involved. Skill mix is an important consideration when implementing new techniques or 
interventions to ensure that these can be successfully integrated into real world clinical practice.  
1.7.3 New technology impact assessment 
Phase 3 will investigate the impact that differing professional groups may have on developing and 
implementing new technologies although the small sample size will preclude any quantitative data 
analysis. A narrative review will be provided.  
1.7.4 Phase 3 sample 
Participants for phase 3 will be invited from the whole cohort of professionals who work within the 
radiology team currently involved with prostate imaging within the Hull University Teaching Hospital 
NHS Trust. This cohort of professionals includes urology specialised radiologists and sonographers 
who are involved with the production and interpretation of prostate imaging, and will also include 
urology consultants and urology registrars who are involved with reading and decision making from 
prostate imaging at multi-disciplinary team meetings. Sonographers in this cohort are radiographers 
who have undertaken Masters level post graduate training in medical ultrasound and specialised in 
specific prostate imaging. Relevant staff employed within this service will be given study information 
leaflets and invited to join the study. The phase 3 cohort will be a maximum of 12 staff members 
from varying professions.  
1.7.5 Conflicts of interest 
Whilst it is important to maintain anonymity within this group, this will be difficult to maintain as the 
numbers of staff within each professional group is small. Data analysis will only be undertaken by 
the lead researcher and all results will be shared sensitively with consideration that confidentiality 
will be maintained at all times. Identifiable data will not be published or shared. The lead researcher 

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who will be involved in the acquisition and scoring of the multi-parametric ultrasound images but 
will not complete a phase 3 survey to prevent bias. However, the lead researcher will complete a 
survey independent of the study at implementation and at 12 months and use this to inform their 
reflection of the study and personal development within their clinical role.  
1.7.6 Lead researcher considerations 
The lead researcher is a key player in the small clinical team and integral in ensuring NHS service 
delivery can be maintained.  The lead researcher is also the clinical lead sonographer for the 
ultrasound service within the trust. It is recognised that this may cause unnecessary conflict and 
bias. To avoid this, and to minimise the risk of coercion consent for participation within phase 3 of 
the study will be obtain by the recognised PhD clinical supervisor, Mr Matthew Simms, Consultant 
Urologist, who is overseeing the clinical aspect of the study with the lead researcher. This potential 
conflict is an acknowledged risk and will be managed by open communication and by ensuring 
participants have the option to withdraw consent to participate at any time with no adverse effects.  
1.7.7 Inclusion criteria for phase 3 
 
Health care practitioner working as a radiologist or sonographer and employed within 
radiology of Hull University Teaching Hospitals NHS Trust 
 
Hold a recognised qualification awarded by the Royal College of Radiologists or a recognised 
post graduate ultrasound qualification undertaken at a CASE approved higher education 
institute 
 
Registered with a statutory regulator such as the GMC, NMC or HCPC 
 
Participates in the current radiology prostate cancer assessment care pathway  
 
Able to provide informed consent to the study 
1.7.8 Exclusion criteria for phase 3 
 
Health care practitioners not employed in Hull University Teaching Hospitals NHS Trust 
 
Sonographers or radiologists not directly participating in the current radiology prostate 
cancer assessment care pathway 
 
Sonographers or radiologists who do not hold relevant qualifications listed within the 
inclusion criteria 
 
Sonographers or radiologists who do not hold relevant statutory registration 
 
Sonographers or radiologists who do not consent to participate in the study  
1.7.9 Phase 3 data collection 
The survey is designed using the tool related to the normalisation process theory. The Normalisation 
MeAsure Development (NoMAD) tool is a questionnaire of survey items used to assess the 

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implementation processes of this new technology. A paper copy of the survey questions is provided 
in Appendix 8. The survey will be created within the JISC (Joint Information Systems Committee) 
online survey tool and distributed anonymously to all participants; it is acknowledged that 
anonymity is difficult to maintain due to the small cohort of staff and the wide variety of individual 
roles.  
1.7.10 Phase 3 participant and data confidentiality 
Confidentiality will be maintained. The responses will be analysed in a simple tabular format 
summarising the frequency of responses to items which will indicate where participants are 
providing more positive or negative responses.  
1.7.11 Data analysis 
A narrative of the qualitative data collected will be produced to identify the main themes that may 
provide an opportunity for development or either technology or skill set of the participant as well as 
identifying the barriers to implementation.  
1.8 Phase 4 
A fourth phase of the study is planned. Once outcomes from the initial 3 phases of the study are 
known the lead researcher intends to participate in a national meeting where results will be 
presented and discussion held between the research team and other centres providing a diagnostic 
prostate cancer service. The lead researcher has experience of planning and organising national 
study events and has access to the British Medical Ultrasound (BMUS) Team who will facilitate. The 
event will be open to all centres providing a prostate service. Notes will be taken during the event to 
form a narrative of proposed service developments. Attendees at the event will be informed that the 
event is being undertaken as an outcome of the research study and will be invited to participate in 
discussions around the study findings and implications for future service delivery.  
1.8.1 Inclusion criteria for phase 4 
 
Delegates attending the specific prostate imaging workshop organised through BMUS 
 
Able to provide informed consent to the study 
 
Delegates who are happy to participate in discussion but who do not want their own 
comments recorded. Reference is made to the Phase 4 consent to study sheet (ICF V2 
03.11.2021) 
1.8.2 Exclusion criteria for phase 4 
 
Delegates attending the study event who do not consent to participate in the study  

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23 
 
Delegates who register for the study event but fail to attend. Notes from face to face 
discussion only will be recorded in the interests of transparency for all participants 
 
1.9 Consent 
Written consent will be obtained from all participants in all three phases of the study.  
1.9.1 Phase 1 consent 
Phase 1 participants will be informed of the study at their initial clinic appointment with a nurse 
practitioner. A leaflet will be given to the men to read prior to attending for their pre-biopsy MRI 
examination. Once the MRI has been completed the men will be contacted by telephone and invited 
onto the study. Those that give verbal consent at that stage will be met by the lead researcher on 
the day of their routine prostate biopsy appointment and written consent will be obtained.  
1.9.2 Phase 2 consent 
All histology results post prostate biopsy are currently recorded in the hospital patient information 
system with the prostate biopsy record. These are discussed at the urology multi-disciplinary 
meeting and decision to treat or offer active surveillance made. Details of men moving onto AS will 
be communicated to the lead researcher by the MDT coordinator using a password protected 
internal hospital database. These men will be contacted by the lead researcher and invited onto 
phase 2 of the study.  
The consent procedure, for both phase 1 and phase 2 of the study, will involve talking to the 
participant, explaining the aims of the research to them, explaining the aims and objectives of the 
study, and explain study procedures, and the possibility to withdraw from the study at any given 
moment without giving any justifications or explanations. The consent form will include permission 
to continue to use data already collected should a participant withdraw from the study.  
Participants will only be included in the study if they are freely able to provide valid consent. 
Consent forms will discuss the issues related to continued participation in the study should the 
participant lose capacity and include permission for continuation of data analysis of data that has 
already been collected should the participant lose capacity to consent. 
1.9.3 Phase 3 consent 
Phase 3 participants will be invited into the study to both undertake multi-parametric ultrasound 
imaging, and to provide a retrospective score of the saved images. Phase 3 participants will also be 
required to undertake 2 surveys to provide their views of the new technology using the NoMAD 

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survey.  The requirements of the study will be fully explained in a leaflet prior to a face to face 
discussion where written consent will be obtained by the lead researcher. Care will be taken to 
ensure there is no conflict between the lead researchers research role and her clinical role to 
prevent coercion of team members participating in the study  
1.10 Risks, burdens and benefits 
1.10.1 Phase 1 
1.10.1.1 Risk 
There is minimal risk to patients participating in phase 1 of the study. A trans-rectal ultrasound 
examination of the prostate will be performed prior to any standard care being undertaken. The 
standard care for patients with MRI PI-RADS score 3, 4 or 5 is to have a transrectal ultrasound probe 
inserted into the rectum, the prostate identified and appropriate biopsy sites determined. The 
majority of men tolerate this procedure well. The multi-parametric US examination will involve a 
probe being inserted into the rectum, images taken and stored for evaluation later. The probe will 
then be withdrawn and standard care will commence.  
1.10.1.2 Burden 
The burden upon the patient is to have two probes separately inserted into the rectum as opposed 
to once for standard care. The examination time will be extended by a maximum of 10 minutes. The 
burden is greater for participants with MRI PI-RADS score of 1 or 2. Rectal ultrasound and biopsy is 
not indicated as part of their standard care pathway and, as such, participation in the study will 
include a transrectal ultrasound examination that they would not normally receive. Both 
examinations will take no more than 10 minutes in total and will be planned around clinic 
attendances to avoid unnecessary visits to the hospital.  
1.10.1.3 Benefit 
The benefit is that the researcher will gain valuable data in terms of stored ultrasound images that 
can be correlated to existing gold standard MRI and histology where available. The patients will have 
the satisfaction of participating in a study evaluating new technology which may lead to better 
outcomes for future patients. The ultrasound imaging is unlikely to be able to provide diagnostic or 
prognostic information until a comparative analysis with the gold standards has been performed. 
However, should any findings of incidental pathology or suspicious appearances be determined 
during the ultrasound examination these will be alerted to the lead clinician. Any such incidental or 
suspicious findings will then be discussed at the urology multi-disciplinary meeting (MDT) to 
determine a management plan. Such findings may result in early detection of potential issues 
providing a benefit to participants on this study.  

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1.10.2 Phase 2 
1.10.2.1 Risk 
There is minimal risk to patients participating in phase 2 of the study. A trans-rectal ultrasound 
examination of the prostate will be performed prior to any standard care being undertaken. 
Standard care includes a PSA blood test and a DRE. A multi-parametric US examination will be 
performed immediately following the regular DRE. It again will involve a probe being inserted into 
the rectum, images taken and stored for evaluation later. This will be repeated with the micro 
ultrasound probe. The probe will then be withdrawn and the patient attendance complete. Both 
examinations will take no more than 10 minutes in total. 
1.10.2.2 Burden 
There is a greater burden to phase 2. This is an examination over and above standard care. The 
patient will need to tolerate a rectal ultrasound examination every 6 months. As this new technology 
is being investigated it is not a diagnostic examination and will not provide diagnostic or prognostic 
results for the individual participant. The burden of dealing with the unknown will be explained to 
the participant and access to urology specialists will be available at all times. Should any findings of 
concern be detected on evaluation of the multi-parametric US these will be alerted to the lead 
urologist and arrangements for MRI will be made. Any changes on MRI compared to the baseline 
imaging will necessitate diagnostic biopsy. 
1.10.2.3 Benefit 
The benefit is that the researcher will gain valuable data in terms of stored ultrasound images that 
can be correlated to previous multi-parametric US, previous existing gold standard MRI and 
histology where available. The patients will have the satisfaction of participating in a study 
evaluating new technology which may lead to better outcomes for future patients.  The ultrasound 
imaging is unlikely to be able to provide diagnostic or prognostic information until a comparative 
analysis with the gold standards has been performed. However, should any findings of incidental 
pathology or suspicious appearances be determined during the ultrasound examination these will be 
alerted to the lead clinician. Any such incidental or suspicious findings will then be discussed at the 
urology MDT to determine a management plan. Such findings may result in early detection of 
potential issues providing a benefit to participants on this study. 
1.10.3 Phase 3 
1.10.3.1 Risk 
There is minimal risk to health care practitioners participating in phase 3 of the study. There is an 
established group of sonographers and radiologists providing the radiology prostate cancer 
assessment care pathway. There is a risk to the study of attrition of participants due to the age 

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demographics of the available workforce and staff relocating. There is also a risk of conflict between 
professional groups as knowledge and skills develop. This will be mitigated by regular 
communication with the study groups, led by the lead researcher and supported by the academic 
supervisory team as a non-involved third party. The greatest risk however is due to the lead 
researcher having a pivotal leadership role within the team and crucial to normal service delivery. 
There is a risk of unintentional bias from participants either feeling they should participate or feeling 
the need to please. These risks will be mitigated by open and honest communication with all team 
members upon recruitment and during the study.  
1.10.3.2 Burden 
There is a burden on the participants in phase 3; this is an additional workload over and above their 
existing activity. However, the ultrasound department is highly supportive of research and 
development and allocates time for such activity within practitioners’ working day. There is a risk 
that the radiologists may have competing workloads which cannot be mitigated against but, again, 
R&D is supported within radiology and this study provides development opportunities for all 
participants.  
1.10.3.3 Benefit 
The participants will have the opportunity to learn new skills and improve their knowledge of this 
common disease. They will be participating in a study with the aim of improving patient care in their 
chosen field of practice. This will, hopefully, engender professional pride, engagement, and 
commitment. The participants will have the opportunity to use and experience new ultrasound 
technology. This study is using the first micro-ultrasound machine installed in the UK and, as such, is 
ground breaking in the UK knowledge of prostate ultrasound imaging.  
1.10.4 Phase 4 
Phase 4 of the study requires the organisation of a study event. There will be little in terms of 
burden on the participants of this event; indeed, it is likely to be hugely beneficial in terms of sharing 
practice and hearing about new technology. The burden will be on the lead researcher who will be 
responsible for organising the event and ensuring an accurate record of discussions in transcribed. 
However, there are benefits of discussion with other health care providers ensuring the research 
does not become single centre-centric and to provide a wider overview of practice that could be 
implemented to better improve local services.  

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1.11 Confidentiality 
This project is a prospective study comprising data from the medical records of patients of Hull 
University Teaching Hospitals NHS Trust, who in keeping with standard clinical care and 
management, have undergone diagnostic tests, treatments and interventions but who will be 
consenting to additional diagnostic imaging examinations. Therefore, in accordance with the Health 
Research Authority (2017), this study requires approval from the Local Research Ethics Committee 
(LREC).  As this study is being undertaken as part of a PhD programme, ethical release has been 
sought from the University of Hull. 
1.12 Approval 
Approval from the Hull University Teaching Hospitals NHS Trust will be sought in line with the local 
Research And Development Operational Policy which is in place to ensure studies adhere to a robust 
ethical framework. Key to this is legislation in the Data Protection Act (2018), General Data 
Protection Regulations (Gov.UK, 2018) and the guidance upheld in the Caldicott Principles 1997. 
Wherever possible sensitive and personal information, which may identify participants, will be 
removed to minimize the risk of data breaches. The Hull University Teaching Hospitals NHS Trust 
data protection policy and procedures will ensure possible data breaches are risk assessed and that 
protection of network drives are maintained and kept current. Unnecessary data will not be stored. 
1.13 Data security 
All data will be collected within the following restrictions:  
Only the data required for the evaluation of the study aims and objectives will be collected. All data 
will be accurately transcribed and analysed within the confines of the requirements of the project. 
The data will be utilised for the specific purpose of this study only.  Consent forms will include 
permission for data access by the primary research team, use of data in publication as well as 
consent for future studies which may originate from this primary study.  
New and emerging technology is used in this study and as such new diagnostic features may become 
evident. As such intellectual property rights are considered and advice is sought from the Hull 
University Teaching Hospitals NHS Trust IP team.  
1.13.1 Incidental or adverse clinical findings 
Consideration is given to incidental pathology or suspicious findings detected as part of the imaging 
component undertaken during the diagnostic data set collection within this study. The consent 

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forms will include permission for the researcher to share any abnormal findings or concerns about 
suspicious findings with the participant’s clinical team to avoid unnecessary delay to diagnosis and / 
or clinical treatment. 
1.14 Conflict of interest 
The major conflict of interest is that the lead researcher is a sonographer and will be going through a 
period of skill development as per the participants in phase 3 of the study. Robust supervision will 
mitigate against undue bias during the phase 3 data collection and analysis. 
Participants may request access to data relating to their own input into the study and will be given 
access to their own record only. No other participant data will be shared. 
1.15 Use of tissue samples in future research 
No human tissue will be stored for future research. All stored data related to this study, including 
images and databases, will be destroyed after 10 years in compliance with the Hull  
 
 

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1.16 
Appendix 1: Evaluating the role of diagnostic ultrasound in prostate cancer – Current clinical 
pathway. Referral to diagnosis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient presents to GP with suspected prostate cancer – referral sent to urology 
department at Castle Hill Hospital.  
Pathway A 
Pathway B 
Age > 75 and / or 
PSA > 20 and / or 
life expectancy < 10 
years 
Transperineal prostate or 
transrectal biopsy under local 
anaesthetic performed (dependent 
upon site of target lesion) 
CT abdomen & pelvis and 
/ or nuclear medicine 
imaging  
Age ≤ 75 and 
PSA ≤ 20 and 
life expectancy 
≥ 10 years 
Multiparametric 
MRI performed  
Multiparametric 
MRI 
contraindicated  
MRI Reviewed. PI-RADS 
1 or 2 – pt offered PSA 
monitoring or biopsy 
MRI Reviewed. 
PI-RADS 3, 4 or 5   
Transperineal prostate 
biopsy under local 
anaesthetic performed 
Histology performed and results reviewed at MDT 
Patients seen in clinic – options for watchful waiting, active surveillance or active treatment 
discussed and agreed 
Patient seen in nurse led clinic and options for diagnosis and possible treatment discussed. 
Patient agrees to investigations. Placed upon relevant pathway as defined by the Trust criteria. 
Referrals for relevant imaging and biopsy sent to radiology 

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1.17 
Appendix 2: Evaluating the role of diagnostic ultrasound in prostate cancer – Phase 1 recruitment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient presents to GP with suspected prostate cancer – referral sent to urology 
department at Castle Hill Hospital. Allocated to clinical pathway A 
Age ≤ 75, PSA ≤ 20 and, life expectancy ≥ 10 years 
Patient informed of ultrasound 
research study and provided with 
Patient seen in nurse led clinic and options for diagnosis and possible treatment discussed. 
Patient agrees to investigations. Patient referred to radiology for MRI and prostate biopsy 
(dependent upon MRI findings) 
MRI performed 
Patient contacted by lead researcher and invited into ultrasound study 
Patient agrees to participate in study 
Transrectal multiparametric ultrasound 
performed and standard set of images saved 
MRI Reviewed and biopsy procedure planned.  
Patient declines study 
inclusion 
Mutually agreed appointment given for study investigation 
PI-RADS 1 or 2 – pt offered PSA 
monitoring or biopsy 
PI-RADS 3, 4 or 5: prostate 
biopsy performed 
Standard care pathway followed 
Patient attends and written consent obtained 
Patient declines investigation – 
Urologist returns referral to GP 
with advice for assessment if 
required in the future 

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1.18 
Appendix 3: Evaluating the role of diagnostic ultrasound in prostate cancer – Phase 2 recruitment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patients seen in clinic – options for watchful waiting, active surveillance or 
active treatment discussed and agreed 
Patients have had investigations for suspected prostate cancer 
which include multiparametric MRI 
MRI PI-RADS 1 or 2 
and declined biopsy 
Any PI-RADS score and had biopsy 
performed. Histology Gleeson score known 
Patient opts for watchful waiting 
or active surveillance. US study 
information leaflet given to pt 
Patient opts for active treatment 
(prostatectomy, radiotherapy, hormone 
therapy for example) 
Patient contacted by lead researcher 
Mutually agreed appointments given for study investigation every 
6 months from initial diagnosis for a period of 2 years’ maximum 
Saved images retrospectively reviewed and scored by reviewer 1 – blinded to 
reviewer 2, MRI and histology 
Saved images retrospectively reviewed and scored by reviewer 1 – blinded 
to reviewer 2, MRI and histology 
Apparent changes on ultrasound imaging 
Clinical project lead informed. Up to date 
PSA obtained. Patient discussed at MDT. 
Options include continue AS, MRI or active 
treatment offered 
No apparent changes on imaging 
Standard watchful waiting / active 
surveillance continues. 
Treatment commenced 
Patient agrees to participate in study 
Patient declines 
Patient attends and written consent obtained 
Transrectal multiparametric ultrasound performed and 
standard set of images saved 
Phase 1 and Phase 2 scores reviewed by lead researcher 
Study participation continues with consent 

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1.19 
Appendix 4: Ultrasound in prostate cancer – Phase 1 Image review pathway 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patients under clinical pathway A  : Age ≤ 75, PSA ≤ 20 and, life expectancy ≥ 10 years 
Patients informed of study and had information leaflets. Patient contacted by lead 
researcher and consented to participate in phase 1 of the study 
MRI Performed and diagnostic report produced utilising PI-RADS V2 scoring system   
Patient attends ultrasound department at 
mutually agreed appointment time. Written 
consent obtained 
Transrectal multiparametric ultrasound performed using both standard 
and micro ultrasound imaging by a sonographer. Sonographer is blinded to 
the previous MRI images and report. Standard set of ultrasound images 
saved under unique identifier on the PACS of Hull Teaching Hospitals Trust 
MRI Reviewed and biopsy procedure planned.  
PI-RADS 1 or 2 – pt offered PSA 
monitoring or biopsy 
PI-RADS 3, 4 or 5: prostate 
biopsy performed 
Standard care pathway followed 
Patient attends but declines 
participation following face to 
face discussion 
Saved images retrospectively reviewed and scored using by randomly allocated reviewer 
1 – blinded to reviewer 2, MRI and histology. Scores saved on protected database 
Saved images retrospectively reviewed and scored by randomly allocated reviewer 2  - 
blinded to reviewer 1, MR and histology. Scores saved on protected database 
MRI Score and histology score for each participant recorded in database by lead researcher. A 
comparison between Reviewer 1 US scores and MRI & histology and between reviewer 2 US scores and 
MRI & histology made.  
Agreement rates between reviewers calculated 
Unique identifier number allocated to patient.  UIN randomly allocated to randomly selected 
reviewer. Team of reviewers recruited from radiology team and who have consented to 
participate in phase 3 of the study 

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1.20 
Appendix 5: Diagnostic ultrasound in prostate cancer – Phase 2 Image review pathway 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patients with previous investigations for prostate cancer which include MRI reported with PI-
RADS V2 scoring system and who have opted for watchful waiting or active surveillance.  
Patients informed of study and had information leaflets. Patient contacted by lead researcher 
and consented to participate in phase 2 of the study 
Patient attends ultrasound department at mutually 
agreed appointment time. Written consent obtained 
Transrectal multiparametric ultrasound performed using both standard 
and micro ultrasound imaging by a sonographer. Sonographer is blinded to 
the previous MRI images and report. Standard set of ultrasound images 
saved under unique identifier on the PACS of Hull Teaching Hospitals Trust 
Patient attends but declines 
participation following face to 
face discussion 
Saved images retrospectively reviewed and scored using by randomly allocated reviewer 
1 – blinded to reviewer 2, previous US, MRI, and histology. Scores saved on database 
Saved images retrospectively reviewed and scored by randomly allocated reviewer 2  - 
blinded to reviewer 1, previous US, MR, and histology. Scores saved on database 
MRI Score and histology score for each participant recorded in database by lead researcher. A 
comparison between Reviewer 1 US scores and MRI & histology and between reviewer 2 US scores 
and MRI & histology made.  
Agreement rates between reviewers calculated 
Unique identifier number of patient randomly allocated to randomly selected reviewer. 
Team of reviewers recruited from radiology team and who have consented to 
participate in phase 3 of the study 
Mutually agreed appointments given for study investigation every 
6 months from initial diagnosis for a period of 2 years’ maximum 
Standard watchful waiting / active surveillance continues. 
Phase 1 US scores and phase 2 US scores reviewed by the lead researcher. 
Apparent changes identified. Any changes to be communicated to clinical project 
lead for discussion at urology / prostate MDT  

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1.21 Appendix 6: Data collection form – Standard Ultrasound 
 

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1.22 Appendix 7 – Data collection form – Micro-ultrasound 
 

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1.23 Appendix 8 – Phase 3 Implementation Survey 
 
 

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37 
 
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