Urodynamics for prostate surgery trial: randomised evaluation of assessment methods

Plain English Summary

Background and study aims
The prostate gland sits around the exit of the bladder in men. As men get older, the prostate grows, and this can narrow the exit from the bladder, so that there is restriction of flow. As a result, some men develop difficulty passing urine (voiding) as they age. For these men, prostate surgery can be helpful by removing the part of the prostate causing the narrowing, so that flow improves. However, for some men, almost identical symptoms of difficulty passing urine are due to underactive bladder. In other words, the bladder contraction is too weak, and is not effective at expelling the urine. This is a smaller group, but important, as these men may have no improvement after prostate surgery, while being exposed to risk of complications of surgery. Medical assessment of men with voiding problems typically involves discussing the symptoms, doing a physical examination of the prostate and measuring the urine flow rate. In many NHS hospitals, these are the only tests done before deciding whether to proceed to prostate surgery. In effect, voiding symptoms are presumed to be a result of prostate enlargement for these men, since it is the more common problem compared with bladder underactivity. However, this approach cannot identify which men actually have bladder underactivity as the cause of their voiding symptoms. So, in some hospitals an extra test is used, called urodynamics. Urodynamics is done to measure how much pressure the bladder generates when passing urine, because a high pressure shows the problem is obstruction, and a low pressure shows it is bladder weakness. Urodynamics involves gently putting a small tube into the bladder via the penis to measure the bladder pressure, and to fill the bladder with a sterile fluid (saline). Another small tube is gently placed into the rectum, via the anus, to measure abdominal pressures. Measuring abdominal pressure is necessary because any change in abdominal pressure can affect bladder pressure, and if the test did not allow for this it could give a misleading result. Urodynamics is safe, but some men find it uncomfortable or undignified, and a few develop urine infection afterwards. No studies have been conducted so far to tell us which of these two approaches to assessing men with voiding urinary problems is better overall.

Who can participate?
UPSTREAM – Phase I: Men who are experiencing bothersome lower urinary tract symptoms (LUTS) and are seeking further treatment, which may include the possibility of having surgery for your symptoms.
UPSTREAM – Phase II: Existing participants of the UPSTREAM trial (UPSTREAM – Phase I)

What does the study involve?
The UPSTREAM project consists of two phases, UPSTREAM – Phase I and UPSTREAM – Phase II.
If you take part in the UPSTREAM – Phase I study, you will be asked to complete a questionnaire and a bladder diary, you will do a flow rate test, and we will check your urine for infection during a hospital visit. You will be assigned at random to have the standard NHS tests either with or without urodynamics. If you are assigned to the urodynamics group, the test will be done at another hospital visit. You will then discuss the results with your urologist and you will decide whether to have surgery, based on the results of the test and the answers to any questions you have for your urologist. You will be asked to complete symptom questionnaires at 6, 12 and 18 months after joining the study. These will analyse your urinary symptoms, your quality of life, satisfaction with testing, sexual function and health outcomes. You will do a follow-up flow rate test (two flow rate tests if you have surgery). You may be asked to have an interview with a qualitative researcher to discuss your opinions in more detail. This study will compare the two methods of assessing symptoms by finding out whether the men had similar relief of their symptoms. We will also study whether the urodynamic tests changed the decision for surgery in some of the men (how many men had surgery in each of the two groups?). We will assess the cost-effectiveness of the two management pathways, and study any side effects of the tests and the treatments.
In the follow-up study (UPSTREAM – Phase II), we want to find out the longer-term (5-year) results of treatment for the men’s LUTS, and see how many men went on to receive surgery after the initial 18-months (i.e. after the original study, “UPSTREAM - Phase I”). In taking part in UPSTREAM - Phase II, men do not need to return to hospital for any clinical assessments. Instead, we will ask them to complete one questionnaire booklet about their urinary symptoms, the effect on their everyday life, and their general state of health. To thank men for their time we will offer them a £20.00 gift voucher upon receipt of the completed questionnaire. We will also securely collect information relevant to this study from central NHS records (such as information about relevant inpatient stays and outpatient attendances).

What are the possible benefits and risks of participating?
UPSTREAM – Phase I: The information will be important for men trying to decide on management of their symptoms, for the doctors advising them, and for the NHS in ensuring the best use is made of resources for this common problem. Side effects of the treatment include urinary infection and urinary retention.
UPSTREAM – Phase II: By taking part, men will be providing evidence for future men with bothersome LUTS who may be faced with similar decisions they and their urologist have had about assessing and treating your condition. We do not anticipate any disadvantages in taking part, although men will need to spend time completing the questionnaire.

Where is the study run from?
For Phase I of the UPSTREAM project, Urology departments of at least 26 NHS hospitals in England were responsible for the recruitment, assessment and treatment of UPSTREAM.
For the purpose of UPSTREAM - Phase II, no clinical assessments are proposed, rather data collection is via PROMS (questionnaires) and data extraction via central NHS records (e.g. NHS Digital linked data). Thus, it is not necessary for men to return to their local hospital, nor will they (or the coordinating research team) require contact with their Urology clinical care team.
The central (coordinating) research team based at the Bristol Randomised Trials Collaboration (BRTC), as part of the Bristol Trials Centre (BTC), will be responsible for coordinating and delivering the study components. North Bristol NHS Trust will have oversight of data collection and responsibility for reporting through the NIHR.

When is the study starting and how long is it expected to run for?
October 2014 to December 2023

Who is funding the study?
National Institute for Health and Care Research (NIHR) (UK)

Who is the main contact?
Mr Marcus Drake
marcus.drake@imperial.ac.uk

Study website

http://www.bristol.ac.uk/population-health-sciences/projects/upstream/

Type

Scientific

Contact name

Mr Marcus Drake

ORCID ID

Contact details

Bristol Urological Institute
Southmead Hospital
Bristol
BS10 5NB
United Kingdom
+44 (0)117 323 5690
marcus.drake@imperial.ac.uk

EudraCT/CTIS number

Nil known

IRAS number

153330, 264738

ClinicalTrials.gov number

NCT02193451

Protocol/serial number

HTA 12/140/01

Scientific title

Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods (UPSTREAM) for diagnosis and management of bladder outlet obstruction (BOO) in men

Acronym

UPSTREAM

Study hypothesis

In men with bothersome lower urinary tract symptoms (LUTS), we hypothesise that diagnostic categorisation of bladder outlet obstruction using invasive urodynamics improves patient selection for obstruction-relieving prostate surgery compared to a pathway with no invasive urodynamic testing. Consequently, this will make it less likely that the subgroup of men with LUTS who do not have bladder outlet obstruction will elect to undergo surgery, thereby reducing risk of harm from surgery and potentially worse symptom outcomes.

More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/1214001
Protocol can be found at: http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0004/117886/PRO-12-140-01.pdf

Added 11/12/2019:
Objectives of UPSTREAM – Phase II:
To answer the following questions at five years post-randomisation:
A. What are the symptomatic outcomes for LUTS, measured by the IPSS?
B. What are the surgery rates in the two diagnostic pathways (the relative proportion of men having surgery)?
C. Was additional diagnostic testing (e.g. UDS) undertaken after the completion of UPSTREAM - Phase I? (where possible)
D. What are the differential effects on other outcomes, such as symptom: severity and bother; sexual function; quality of life (QoL); and general health?
E. What is the cost-effectiveness from an NHS secondary care perspective using the QALY as the economic outcome?
F. What is the differential use of NHS resources?

Ethics approval(s)

Phase I: NRES Committee South Central - Oxford B, 10/07/2014, REC ref: 14/SC/0237
Phase II: South Central – Berkshire, 01/11/2019, REC ref: 19/SC/0578; HRA approval 04/11/2019

Study design

Phase I: Randomised controlled parallel-group trial
Phase II: Further follow up (five years post-randomisation) of the UPSTREAM randomised controlled trial (RCT)

Primary study design

Interventional

Secondary study design

Randomised parallel trial

Study setting(s)

Hospital

Study type

Diagnostic

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Lower urinary tract symptoms; Urodynamics

Intervention

A care pathway based on urodynamic tests with invasive multichannel cystometry ('invasive urodynamics' active intervention arm) and a care pathway based on non-invasive tests, i.e. without multichannel cystometry ('usual care' control arm).

Intervention type

Other

Primary outcome measure

Difference in lower urinary tract symptom (LUTS) between the two arms at 18 months, measured with the International Prostate Symptom Score (IPSS)

Secondary outcome measures

Current secondary outcome measures as of 05/02/2019:
1. Surgery rate (the relative proportion of men in each group having surgery up to 18 months after randomisation).
2. Cost-effectiveness analyses from the perspectives of the NHS, Personal Social Services and patients. Subsequent need for surgery will be recorded.
3. Adverse events of testing and treatment (e.g. infection, urinary retention).
4. Measures from the International Consultation on Incontinence Questionnaires (ICIQ) (Abrams et al., 2006) will be used alongside the IPSS, giving sensitive and comprehensive assessment of LUTS severity/ bother, sexual function, quality of life and satisfaction with urodynamic testing. The following will be measured at 6, 12 and 18 months:
4.1. IPSS
4.2. ICIQ Male LUTS (ICIQ-MLUTS)
4.3. ICIQ sexual function in Male LUTS (ICIQ-MLUTS-sex)
4.4. ICIQ urodynamics satisfaction (ICIQ-UDS-S) will be administered at a single time point after urodynamic testing for relevant patients.
5. Maximum urinary flow rate (Qmax) at 18 months. In men undergoing surgery in both arms, an additional Qmax measure at 4 months after operation will be used as a quality measure for surgery.
6. The EQ-5D-5L will be used to provide the quality of life weights used to calculate Quality Adjusted Life Years (QALYs).
7. Qualitative interviewing will explore user acceptability and influences on decisions made by the participating men and the surgeons.

UPSTREAM – Phase II (added 11/12/2019):
1. LUTS measured with the IPSS PROM at 5 years post-randomisation (objective A)
2. Alongside the IPSS (including the QoL measure), measures from selected International Consultation on Incontinence Questionnaires (ICIQs) will be used, collectively giving sensitive and comprehensive assessment of QoL, LUTS severity/bother, sexual function, and general health (objective D). The following measures will be used:
2.1. IPSS – including QoL
2.2. ICIQ Male LUTS (ICIQ-MLUTS)
2.3. ICIQ sexual function in Male LUTS (ICIQ-MLUTS-sex)
3. The EQ-5D-5L will be used to provide the QoL weights used to calculate QALYs (objective E)
4. Data for objectives ‘B’ (surgery rates), ‘C’ (diagnostic testing), and ‘F’ (resource use) will be obtained via a one-off bespoke data extraction of Health Episode Statistics (HES) and HES-Office of National Statistics (ONS) linked data via NHS Digital.
5. PROMs (standardised questionnaires) will form the “5-year follow up” questionnaire booklet, which will be completed at each participant’s 5 years post-randomisation timepoint, or thereabouts (objectives A, D and E). Participants will be able to complete the questionnaire booklet via post, online or telephone.
6. Data extraction via NHS Digital: to assess surgery rates, whether additional diagnostic testing was undertaken after the completion of UPSTREAM - Phase I (where possible), and resource use (objectives B, C and F) the researchers will utilise individual-level data obtained via a bespoke data extraction of HES and HES-ONS linked data, via NHS Digital. The data extraction will include individual-level data about participants’ relevant: inpatient stays; outpatient attendances: including procedures; radiology and accident and emergency (A&E) episodes; and cause of death (where applicable).
The researchers envisage the extraction taking place in 2022 to (ideally) include the last participant’s 5-year post-randomisation timepoint. The exact date of extraction, however, will be decided in collaboration with NHS Digital to maximise data collection. The researchers may conduct an earlier extraction to inform the data analysis; this will be decided as the trial progresses.

Previous secondary outcome measures:
1. Surgery rate (the relative proportion of men in each group having surgery up to 18 months after randomisation).
2. Cost-effectiveness analyses from the perspectives of the NHS, Personal Social Services and patients. Subsequent need for surgery will be recorded.
3. Adverse events of testing and treatment (e.g. infection, urinary retention).
4. Measures from the International Consultation on Incontinence Questionnaires (ICIQ) (Abrams et al., 2006) will be used alongside the IPSS, giving sensitive and comprehensive assessment of LUTS severity/ bother, sexual function, quality of life and satisfaction with urodynamic testing. The following will be measured at 6, 12 and 18 months:
4.1. IPSS
4.2. ICIQ Male LUTS (ICIQ-MLUTS)
4.3. ICIQ sexual function in Male LUTS (ICIQ-MLUTS-sex)
4.4. ICIQ quality of life (ICIQ-QoL)
4.5. ICIQ urodynamics satisfaction (ICIQ-UDS-S) will be administered at a single time point after urodynamic testing for relevant patients.
5. Maximum urinary flow rate (Qmax) at 18 months. In men undergoing surgery in both arms, an additional Qmax measure at 4 months after operation will be used as a quality measure for surgery.
6. The EQ-5D-5L will be used to provide the quality of life weights used to calculate Quality Adjusted Life Years (QALYs).
7. Qualitative interviewing will explore user acceptability and influences on decisions made by the participating men and the surgeons.

Overall study start date

01/04/2014

Overall study end date

31/12/2023

Reason abandoned (if study stopped)

Participant inclusion criteria

UPSTREAM – Phase I:

Current inclusion criteria as of 05/02/2019:
1. Men seeking further treatment for their bothersome lower urinary tract symptoms (LUTS) which may include surgery
2. Willing to be randomised

Previous inclusion criteria:
1. Men considering undergoing surgery as a treatment option for their bothersome LUTS
2. Willing to be randomised

UPSTREAM – Phase II (added 03/12/2019):

PROMS (questionnaire) study component:
Inclusion criteria: Men randomised (enrolled) to the UPSTREAM trial (Phase I) who were willing to be contacted for long term follow up, as indicated on their original (Phase I) consent form.

NHS Digital data extraction study component:
Inclusion criteria: Men randomised (enrolled) to the UPSTREAM trial (Phase I).

Participant type(s)

Patient

Age group

Adult

Sex

Male

Target number of participants

800

Total final enrolment

820

Participant exclusion criteria

UPSTREAM – Phase I:

Patients who:
1. are unable to pass urine without a catheter (urinary retention)
2. have a relevant neurological disease
3. undergoing active treatment, or on active surveillance, for prostate or bladder cancer
4. have previously had prostate surgery
5. are not medically fit for surgery, or unable to complete outcome assessments
6. do not consent to be randomised

UPSTREAM – Phase II (added 03/12/2019):

PROMS (questionnaire) study component:
1. Patients who are not already randomised (enrolled) to the UPSTREAM trial (Phase I)
2. UPSTREAM (Phase I) participants who:
2.1. are not willing to be contacted about long term follow up
2.2. have withdrawn trial participation, or at least withdrawn permission to be contacted in the future for long term follow up, at the time of their 18-month timepoint
2.3. do not consent and/or are not willing or able to comply with essential study procedures of this further follow up (UPSTREAM - Phase II)

NHS Digital data extraction study component:
1. Patients who are not already randomised (enrolled) to the UPSTREAM trial (Phase I)
2. UPSTREAM (Phase I) participants who have withdrawn permission for the study to continue to access sections of their medical notes and NHS records, ONS and NHS Central registers information, at the time of their 18-month timepoint

Recruitment start date

01/04/2014

Recruitment end date

31/12/2016

Countries of recruitment

England, United Kingdom

Study participating centre

Southmead Hospital
Bristol
BS10 5NB
United Kingdom

Study participating centre

Freeman Hospital
Newcastle upon Tyne
NE7 7DN
United Kingdom

Study participating centre

Royal Devon and Exeter Hospital
Exeter
EX2 5DW
United Kingdom

Study participating centre

Musgrove Park Hospital
Taunton
TA1 5DA
United Kingdom

Study participating centre

Southport and Formby District General Hospital
Southport
PR8 6PN
United Kingdom

Study participating centre

Kingston Hospital
Kingston upon Thames
KT2 7QB
United Kingdom

Study participating centre

Royal Hallamshire Hospital
Sheffield
S10 2JF
United Kingdom

Study participating centre

Epsom General Hospital
Epsom
KT18 7EG
United Kingdom

Study participating centre

Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom

Study participating centre

Kent and Canterbury Hospital
Canterbury
CT1 3NG
United Kingdom

Study participating centre

Salisbury District General Hospital
Salisbury
SP2 8BJ
United Kingdom

Study participating centre

Lister Hospital
Stevenage
SW1W 8RH
United Kingdom

Study participating centre

Churchill Hospital
Oxford
OX3 7LE
United Kingdom

Study participating centre

The James Cook University Hospital
Middlesbrough
TS4 3BW
United Kingdom

Study participating centre

The Queen Elizabeth Hospital
King's Lynn
PE30 4ET
United Kingdom

Study participating centre

Royal Free Hospital
London
NW3 2QG
United Kingdom

Study participating centre

Royal Liverpool and Broadgreen University Hospitals NHS Trust
Liverpool
L7 8XP
United Kingdom

Study participating centre

Torbay Hospital
Torbay
TQ2 7AA
United Kingdom

Study participating centre

Southampton General Hospital
Southampton
SO16 6YD
United Kingdom

Study participating centre

Kettering General Hospital
Kettering
NN16 8UZ
United Kingdom

Study participating centre

Charing Cross Hospital
London
W6 8RF
United Kingdom

Study participating centre

Royal Berkshire Hospital
Reading
RG1 5AN
United Kingdom

Study participating centre

Derriford Hospital
Plymouth
PL6 8DH
United Kingdom

Study participating centre

West Cumberland Hospital
Whitehaven
CA28 8JG
United Kingdom

Study participating centre

Sunderland Royal Hospitals
Sunderland
SR4 7TP
United Kingdom

Study participating centre

St George’s Hospital
London
SW17 0QT
United Kingdom

Organisation

Southmead Hospital (UK)

Sponsor details

c/o Helen Lewis
Research and Innovation Office
Floor 3 Learning and Research
Bristol
BS10 5NB
England
United Kingdom
+44 (0)117 323 6468
helen.lewis@nbt.nhs.uk

Sponsor type

Hospital/treatment centre

Website

ROR

https://ror.org/05d576879

Funder type

Government

Funder name

Health Technology Assessment Programme

Alternative name(s)

NIHR Health Technology Assessment Programme, HTA

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Publication and dissemination plan

Results will be published in peer-reviewed journals.

Intention to publish date

31/12/2024

Individual participant data (IPD) sharing plan

Anonymous research data will be stored securely and kept for future analysis. Members of the PMG will develop a data sharing policy consistent with UoB policy. Data will be kept anonymous on secure access computers. Requests for access to data must be via a written confidentiality and data sharing agreements (DSA), which will be confirmed by the CI (or appointed nominee); DSA templates are, for example, available from the University of Bristol’s research data services facility (RDSF) website.
The DSA should cover limitations of use, transfer to 3rd parties, data storage and acknowledgements. The person applying for use of the data will be scrutinised for appropriate eligibility by members of the research team. All requests will require their own separate REC approval prior to data being released.

IPD sharing plan summary

Available on request

Study outputs

• ISRCTN56164274_PROTOCOL_V1.0_21Oct19.pdf
• ISRCTN56164274_ResultsPlainEnglish.docx