Trial background

Some men develop difficulty passing urine (voiding) as they age. This may be because an enlarged prostate gland (which sits round the base of the bladder) narrows the bladder outlet (urethra) or because the bladder becomes less able to contract. Prostate surgery is more likely to help symptoms in the first group, while the second group may have no improvement after surgery, while being exposed to risk of complications of surgery.

Invasive urodynamics involves putting a tube (catheter) into the bladder via the penis, and another into the rectum, to measure bladder and abdominal pressures while the bladder is filled with a sterile fluid. Invasive urodynamics can measure bladder pressures during filling and voiding, and bladder outlet obstruction pressures. The procedure is considered safe, but some men find it uncomfortable or undignified, and a few develop urine infection afterwards. We think that it could be useful to select the men who should and should not have surgery. However, no studies have been conducted so far to tell us if this is true: UPSTREAM is designed to find out if the invasive tests are worthwhile.

UPSTREAM is a randomised controlled trial in men who have bothersome difficulty passing urine, and who are seeking further treatment, which may include having surgery for the symptoms. The group studied will be men who continue to be bothered by difficulty passing urine, despite initial treatment such as drugs, where symptoms are thought to be due to bladder outlet obstruction. The men will be assigned at random to either urodynamic tests as well as the standard non-invasive tests (“Urodynamics”) or to the routine standard tests (“Non-urodynamic assessment” control arm) alone - please see below for more details about the two intervention groups.

The key aims of the UPSTREAM trial are to:

1) Determine whether a care pathway not including invasive urodynamics is no worse for men in terms of symptom outcome that one in which it is included, at 18-months (after randomisation)

2) Establish whether inclusion of invasive urodynamics reduces rates of bladder outlet surgery

Other research outcomes are detailed below.

Intervention groups

Men will be assigned at random (i.e. by chance) to one of two intervention groups:

1) Urodynamic tests as well as the standard non-invasive tests (“Urodynamics” intervention arm),

or

2) Routine standard tests alone (“non-urodynamic assessment” control arm)

Routine standard tests include: asking men to complete a questionnaire (the International Prostate Symptom Score (IPSS)) and a bladder diary; carrying out flow rate testing; and checking the urine for infection. Some surgeons also use “discretionary tests” such as the PSA cancer-screening blood test.

After diagnostic testing with (intervention arm) or without (non-urodynamic assessment control arm) urodynamics, patients will see their surgeon to decide on whether to proceed to surgical treatment. As UPSTREAM is a pragmatic trial, standard practice for the research centres (hospitals) will be followed, relating to the type of surgery, whether to stay on lower urinary tract symptom (LUTS) medication, antibiotic prophylaxis and other factors.

Outcomes

The UPSTREAM trial will compare the two methods of investigation by finding out whether the men had similar relief of their symptoms, by measuring the change in the international prostate symptom score (IPSS) in the two groups at 18 months after randomisation.

We will also look at the following secondary outcomes:

• Whether the invasive tests changed the decision for surgery in some of the men (how many men had surgery in each of the two groups?)
• The cost-effectiveness of the two management pathways
• Adverse effects at 6, 12 & 18 months of (a) the tests and (b) the treatments (e.g. urinary infection, urinary retention)
• Urinary symptoms at 6, 12 & 18 months, using the International Consultation on Incontinence Questionnaires (ICIQ) and the Male Lower Urinary Tract Symptoms questionnaire (ICIQ-MLUTS)
• Sexual function, using the ICIQ-MLUTS sex questionnaire
• Satisfaction with urodynamic testing, using the ICIQ-UDS-S questionnaire
• The maximum urinary flow rate (Qmax) at 18 months
• Health outcomes, using the EQ-5D-5L questionnaire
• Qualitative interviewing will explore user acceptability of urodynamics and influences on decisions made by the participating men and the surgeons

We worked out that 400 men would need to be recruited to each arm of the trial to detect a difference of one point on the IPSS, which is the main clinical measure of the symptoms. Allowing for men who do not want to participate, and who drop out once the trial starts, we would need to approach ≥3800 men during an 18 month recruitment period to reach the required number in each arm.

Please see the Information for patients section for a clear explanation of how we will collect the necessary data, and when, from patients.