Title: Male synthetic sling versus Artificial urinary Sphincter Trial for men with urodynamic stress incontinence after prostate surgery: Evaluation by Randomised controlled trial (MASTER)
Funder: Department of Health and Social Care

Abstract: A pragmatic multicentre randomised controlled non-inferiority trial comparing the effectiveness of the synthetic sling (‘male sling’) with the artificial urinary sphincter (AUS) for men with urodynamic stress incontinence (USI) after prostate surgery (radical prostatectomy or transurethral resection of the prostate; TURP). Health technologies being assessed: Both interventions involve the surgical implantation of a prosthetic device designed to restore continence by specialist urological surgeons. The trial will take place within designated NHS hospitals with the appropriate expertise to implant either the male sling or the AUS. Surgical procedures and other operative variables will be standardised by using agreed protocols. The male sling is a strip of plastic mesh that is placed under the urethra through an incision under the scrotum with each end passed through the obturator foramen into the upper thigh. It is then tensioned to elevate and partially compress the urethra. It is designed to be effective immediately although maximum benefit may take a few weeks to develop. The AUS is a three-part device. A fluid filled plastic cuff is placed circumferentially around the urethra which is accessed through an incision under the scrotum. The cuff is then connected by internalised plastic tubing to firstly a fluid filled pressure-regulating balloon and secondly a small mechanical pump. The balloon is placed in the retropubic space and the pump in a sub-cutaneous pocket in the scrotum. After implantation, the device is initially deactivated with the cuff empty. The man then returns to hospital typically four to six weeks after surgery for activation. He then has to learn how to operate the device. This requires three squeezes of the control pump in the scrotum to empty the cuff and allow voiding. The cuff then automatically refills over 2-3 minutes to restore continence. Setting: All surgeons carrying out AUS or male sling implantation in the UK have agreed to take part. This encompasses 23 centres: Belfast; Birmingham, Bristol; Cambridge; Cardiff; Chichester; Edinburgh; Glasgow; Leicester; Liverpool/Southport; London (2); Manchester; Middlesbrough; Newcastle, Norwich; Oxford; Salisbury; Sheffield; Stockport; Swansea; Wakefield; and Wrexham. We are confident that the trial can recruit to target exclusively in the UK. However, the applicants have collaborations with colleagues throughout Europe, particularly in Belgium and The Netherlands and the protocol would be made available for their participation if agreed and separately funded. Target population: Men with urodynamic stress incontinence (USI) after prostate surgery (radical prostatectomy or TURP), for whom surgery is judged appropriate following discussion of options between patient and clinician. For the purposes of the trial we will define men with mild incontinence as those not requiring surgery. There is no clear threshold for defining moderate or severe incontinence and little evidence of differential benefit for either intervention according to incontinence severity. We will therefore include all men whose degree of incontinence is sufficient to require surgery, from both the patient and surgeon perspectives. Measurement of costs and outcomes: The primary outcome on which non-inferiority will be judged will be participant’s report of urinary incontinence at 12 months measured by a response indicating any loss of urine to either of the two questions: “How often do you leak urine?” and “How much urine do you leak?” in the validated ICIQ-Short Form questionnaire. Twelve months was chosen since maximum benefit of the implantation device is likely to have accrued and any harms directly related to the peri-operative period will have occurred and been resolved. The primary economic outcome will be incremental cost per quality-adjusted life-year (QALY) measured using the EQ-5D at 24 months to allow for the possible need for re-intervention after failure of primary procedure. Secondary outcomes: Other measures of urinary incontinence (ICIQ-Score, urinary diaries and use of pads); condition-specific and generic quality of life; erectile function; health care resource use; and satisfaction with treatment. These outcomes will be measured by questionnaires at baseline, 6 (postal), 12 (clinic), and 24 months (postal), and by a case report form. The 24-hour urinary pad test will be used at baseline and 12 months as quantification of urine loss. The secondary economic outcomes will include costs to the NHS, patients and their families and the EQ-5D scores over the 24 months. Costs will be collected using data report forms completed by trial staff and participant-completed questionnaires. In addition, all men who have surgery, including those ineligible or who do not agree to randomisation, will be asked to consent to long term follow up, including use of computerised NHS records and other routine data sources.

Lay abstract: Around 1 in 5 men who undergo prostate surgery for cancer or benign disease need to use incontinence pads because of leakage of urine when they walk around, cough, or do any physical exertion. This ruins their quality of life, greatly lowers their self esteem, stops them working, and damages their personal relationships. At present the only effective surgical treatment is insertion of a plastic artificial urinary sphincter (AUS) device, which involves a major operation to place an inflatable cuff around the urine pipe close to the bladder, and inflating it to prevent leakage. The man then has to deflate the cuff by repeatedly squeezing a pump placed in his scrotum, to allow him to pass urine when needed. About 350 AUS are put in each year with a total cost to the NHS of £2.7 million. Recently, a new male sling has been developed which when inserted under the urine pipe supports the outlet of the bladder but doesn’t need a pump. It is less expensive for the NHS, easier to insert, but some men may still need a subsequent operation to place an AUS if they feel their incontinence has not improved enough. It is also uncertain whether there are other advantages or disadvantages compared to the AUS, and whether men will be as satisfied with the results. It is important for the NHS to decide whether the male sling or AUS is better because the number of men needing this type of surgery is likely to increase. This is because more men are requiring surgery for early prostate cancer with wider use of the PSA blood test. If our trial shows that the male sling is as good as the AUS and is preferred by men having this surgery, as well as being cheaper, it will help men, their doctors and the NHS planners decide which treatments should be available. We will ask men who are considering having surgery for urine leakage to consent to treatment with either the male sling or AUS. The type of surgery will be decided at random by computer. We anticipate that we will need 3 years to recruit sufficient men for the trial to be successful. Computer randomisation is the most ethical and appropriate design because it gives a fair comparison between the treatments and allows us to be sure that any differences between the results for the two operations are due to the treatment they received in the trial, and not due to other differences which we cannot measure. The trial will take place in hospitals where surgeons are already experienced in carrying out both types of surgery. The success of surgery will be judged by the men’s report of urine leakage, using postal questionnaires at 6 and 12 months after operation. Other outcomes we will measure will include their satisfaction with treatment, sexual function, 24-hour pad tests, quality of life, adverse effects, costs, and use of health services. The men will also be followed up in the longer term to make sure early success is maintained. The main ethical issues are the need for men who take part to accept the treatment they are allocated to by the computer randomisation and the burden of completing the measurements we need to take to find out which treatment is best. As far as we know there is not a great difference in terms of benefits and harms between the two treatments and if men who have the male sling surgery are dissatisfied with the results they can still go on to have AUS surgery. Through our previous work we have limited the amount of paper work and questionnaire completion to a minimum and will also make the questionnaires available on the internet and by text message. The research team includes surgeons who are experts in caring for men with incontinence and in clinical research, together with experts in the design, successful conduct, analysis and reporting of clinical trials in the NHS. We also have the benefit of a patient advisor to make sure that the trial addresses matters of most concern to men with incontinence.

Research activity codes: 6.3 MEDICAL DEVICES;8.2 HEALTH AND WELFARE ECONOMICS
Health categories: RENAL AND UROGENITAL