TOMUS

Retropubic versus Transobturator Midurethral Slings for Stress Incontinence; Richter et al; N Engl J Med. 2010 Jun 3;362(22):2066-76.

Clinical Question

In women suffering from stress incontinence undergoing surgical intervention is retropubic compared to transobturator urethral slings effective (objective and subjective) in treating stress incontinence at 12 months?

Bottom Line

At 12 months outcomes between either method are similar. Differences in complications should be discussed with patients considering surgical treatment for stress incontinence.

Major Points

At 12 months, objective success between retropubic and transobturator approaches were similar and equivalent. The subjective success was similar but non-equivalent. Nil significant differences between groups in post-operative urge incontinence Either method has different complications which should be discussed with patients.

Guidelines

American Urological Association: https://www.auanet.org/guidelines/guidelines/stress-urinary-incontinence-(sui)-guideline Grade A evidence for In index patients considering surgery for stress urinary incontinence, physicians may offer the following options: (Strong Recommendation; Evidence Level: Grade A) Midurethral sling (synthetic) Autologous fascia pubovaginal sling Burch colposuspension Bulking agents

RANZCOG statement on Mid Urethral Slings (MUS): https://ranzcog.edu.au/RANZCOG_SITE/media/RANZCOG-MEDIA/Women%27s%20Health/Statement%20and%20guidelines/Clinical-Obstetrics/MUS-(C-Gyn-32)-Re-write-July-2020_1.pdf?ext=.pdf

There is robust evidence to support the use of traditional MUS from over 2,000 publications making this treatment the most extensively reviewed and evaluated surgical procedure for female stress urinary incontinence. RANZCOG supports the use of synthetic MUS for surgical treatment when conservative treatment has been unsuccessful. There are different risks and long-term outcomes from different surgical approaches which need to be discussed and tailored to each individual woman.

Australia and New Zealand Continence Foundation: https://usanz.org.au/publicassets/aa15ff5d-245c-ea11-90fb-0050568796d8/PublicationArticleAustraliaandNewZealandContinenceFoundationJournalEditorialThemidurethralslingcurrentissuesV23No4Summer2017.pdf Key take-home points are outlined in Box 1. Women with uncomplicated SUI will generally benefit from conservative measures attended to by a continence service. Those who have no relief of symptoms may consider surgery as a reasonable next step. Index patients who have demonstrable SUI without concomitant issues such as Pelvic Organ Prolapse (POP) may be offered an MUS. In women with significant POP, repair of the prolapse in addition to a tension-free MUS or other anti-incontinence technique may be considered. Continence success from treatment using either the RP or TO route is similar but the complication profile is different.

Design

• Randomised, multicentre equivalence trial.
• N=597
  • Retropubic sling (n=298)
  • Transobturator sling (n=299)
• Setting: 9 centres in the USA
• Enrollment: April 2006-June 2008
• Mean follow-up: 12 month timepoint reported.
• Analysis: per protocol (with supporting intention to treat)
• Primary outcome:
  • Objective: negative provocative stress test, negative 24 hour pad test, no additional treatment
  • Subjective: absence of self reported symptoms (using MESA instrument), no leakage in three day diary, no additional treatment

Population

Inclusion Criteria

Women 21 years of age or older who were planning to undergo surgery for the treatment of stress incontinence with:

• at least a 3-month history of symptoms of urinary incontinence that were predominantly or solely associated with stress incontinence (as compared with urge incontinence) AND
• a positive urinary stress test at a bladder volume of 300 ml or less (urodynamic stress leakage not required)
• Medical, Epidemiological and Social Aspects of Aging (MESA) stress symptom score (percent of total possible stress score) greater than MESA urge symptom score (percent of total possible urge score)
• Bladder capacity ≥ 200ml by stress test
• Post-void residual (PVR) ≤ 100cc with pelvic organ prolapse (POP) Stage I or lower. If POP is Stage II-IV, PVR >100cc but ≤ 500cc is allowed
• Eligible for both retropubic and transobturator procedures
• No medical contraindications, e.g., current urinary tract infection (UTI), history of pelvic irradiation, history of lower urinary tract cancer
• American Society of Anesthesiologists (ASA) class I, II, or III
• No current intermittent catheterization
• Available for 24-months of follow-up and able to complete study assessments, per clinician judgment
• Signed consent form

Exclusion Criteria

• Age <21 years
• Non-ambulatory (ambulatory with assistive devices does not exclude the patient)
• Pregnancy by self-report or positive pregnancy test, or self-reported intention to ever become pregnant
• Current chemotherapy or current or history of pelvic radiation therapy
• Systemic disease known to affect bladder function (i.e., Parkinson's disease, multiple sclerosis, spina bifida, spinal cord injury or trauma)
• Urethral diverticulum, current or previous (i.e. repaired)
• Prior augmentation cystoplasty or artificial sphincter
• Implanted nerve stimulators for urinary symptoms
• History of synthetic sling for stress urinary incontinence
• <12 months postpartum
• Laparoscopic or open pelvic surgery <3 months
• Current evaluation or treatment for chronic pelvic pain (painful bladder syndrome)
• Participation in another treatment intervention trial that might influence the results of this trial
• Need for concomitant surgery requiring an abdominal incision, use of graft material in the anterior compartment, or any use of synthetic graft material
• Enrollment in other urinary incontinence trials

Baseline Characteristics

No baseline differences between the groups are highlighted. Characteristics are listed for the Retropubic sling group:

• Age – 52.7 years
• Non-hispanic white – 80.5%
• Married – 68.1%
• BMI - 30.6
• Vaginal deliveries (1 or 2) 49%

Interventions

Urodynamic testing, according to standardized protocols, was performed before and 12 months after surgery in accordance with International Continence Society guidelines. Preoperative urodynamic test results were interpreted by an investigator other than the study surgeon. Retropubic sling used: Tension-free Vaginal Tape (Gynecare) Transobturator slings used: Tension-free Vaginal Tape Obturator (Gynecare), or Monarc (American Medical System)

Outcomes

Comparisons are intensive therapy vs. standard therapy.

Primary Outcomes

• Objectively assessed success rate was 80.8% in retropubic sling group and 77.7% in transobturator sling group
  • With 3% point difference and 95% CI; -3.6 to 9.6, the objective success rate met the criteria for equivalence
• Subjectively assessed success rate was 62.2% in retropubic sling group and 55.8% in transobturator sling group
  • With 6.4% point difference and 95% CI; -1.6 to 14.3, the subjective success rate did not meet the criteria for equivalence
• The rates of patient satisfaction with the treatment were similar between the retropubic-sling group and the transobturator-sling group (85.9% and 90%, respectively; P=0.14).
• There were no significant differences between the groups in quality of life outcomes (P>0.05)

Secondary Outcomes

• There was no change in rate of treatment success in objective or subjective criteria when values were adjusted for Valsalva leak-point pressure and the maximal urethral closure pressure.
• No interaction between treatment and Valsalva leak-point pressure (P = 0.47 Objective success, P = 071 subjective success) and the maximal urethral closure pressure (P = 0.29 Objective success P = 0.38 subjective success)
• Two different surgical approaches were employed for the transobturator sling; the in-to-out and out-to-in method.
  • No significant difference in objective or subjective treatment success were observed between the two methods (P = 0.96 and P = 0.87 respectively)
• Estimated blood loss and operation time was:
  • Higher in retropubic sling group than in the transobturator sling group (50ml vs 25 ml and 30min vs 25 min)

Subgroup Analysis

Patient who underwent concomitant vaginal surgery:

• Had significantly higher success according to objective criteria (P = 0.015)
• However treatment success was the same according to subjective criteria (P = 0.46)

Adverse Events

Adverse events in retropubic sling.

• Bladder perforations and voiding dysfunctions were uncommon but only observed in retropubic sling.
• More than 100ml post-void residual volume at the time of hospital discharge (P = 0.02).
• Higher post op UTI (P = 0.04)

Adverse events in transobturator sling:

• More vaginal perforations were noted (13 vs 6), especially with the in-to-out approach
• Higher neurological symptoms (P = 0.01) with weakness in the upper leg as the most common presentation

Criticisms

• Slings - is this appropriate treatment for stress incontinence?
  • Yes, current guidelines by the International Continence Society recommends (grade A) urethral slings (or other forms of specialised management) in women who have stress incontinence that persists despite initial management options
• Is 12 months a good time frame?
  • International Continence Society Guidelines recommend urodynamic studies at 12 months post-operative
  • Inclusion criteria specified that women should be available for 24 months of follow-up
  • Cochrane review in 2017 on mid-urethral slings made this suggestion: "A salient point illustrated throughout this review is the need for reporting of longer‐term outcome data from the numerous existing trials. This would substantially increase the evidence base and provide clarification regarding uncertainties about long‐term effectiveness and adverse event profile."
• Variation in operators and centres (being multi-centred - different protocols/practice techniques could have contributed to complications
• Power of less than 80% (were aiming for 80% if each arm had 294 - analysis completed with slightly less numbers) - ideally would like above 90% - increasing study size may show statistical significance primary outcomes or increase confidence that there is no difference in rectopubic and transobturator midurethral sling techniques.
• Patients randomised to treatment arms once anaesthetised
  • Used permuted-block randomisation with stratification according to clinical location
  • No significant differences in baseline data across arms
• Patients informed of procedure performed in the post-operative period
  • Surgeons aware of intervention but not aware of pre-operative urodynamic testing results (unless required for the management of post-operative care)
  • Surgeons declared type of transobturator sling (as 2 types used) before study commenced
  • Concomitant vaginal surgery permitted
  • Some concerns of bias with unblinding of patients post-operatively and before outcomes assessed
• Primary outcome (objective) measured through stress testing and pad testing, and whether retreatment was required
  • Subjective through a standardised questionnaire (MESA), 3 day voiding diary and whether retreatment was required
  • Appropriate measurement given baseline testing and inclusion criteria for the trial
  • Same measurement outcomes applied to each group
  • Unable to ascertain whether outcome assessors were aware of intervention arm when completing post-intervention assessment
    • Small potential for influencing subjective outcome data with knowledge of intervention arm (unpredictable), less likely for objective outcome data
• Data analysed as per the pre-specified analysis plan
• Low concerns of bias overall - with unpredictable direction towards either intervention arm of the study

Funding

• The National Institute of Health/National Institute of Diabetes and Digestive and Kidney Diseases/National Institute of Child Health and Human Development/Ethicon Women’s Health and Urology - for the Urinary Incontinence Treatment Network (including travel expenses for meetings/study requirements/etc)
• Allergan (pharma), Pfizer, and Q-Med, in addition to payment for development of educational presentations, and reimbursement of travel and accommodation expenses.

Further Reading

2017 Cochrane Review on Mid-Urethral Slings (Meta-analysis): https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006375.pub4/full