European Urology

1. Introduction

Midurethral slings (MUS), retropubic tension-free vaginal tapes (RP-TVT) [1], and the transobturator tension-free vaginal tapes (TO-TVT) [2] and [3] are the most commonly performed procedures for surgical treatment of stress urinary incontinence (SUI) in women. Two types of TO-TVT have been performed over the last 8 yr— the inside-out (TVT-O) [2] and the outside-in transobturator tape (TOT) [3] approaches—with the choice of the surgical approach predominantly driven by surgeon preference. The lack of consensus in practice among surgeons is likely to be multifactorial, but lack of high-quality comparative studies is an important cause of clinical uncertainty.

The Evaluation of Transobturator Tapes (E-TOT) study [4] was the first high-quality randomised controlled trial (RCT) of the two types of TO-TVT that confirmed no significant difference in patient-reported success rates following either procedure after 1-yr follow-up. A clinically significant improvement in women's quality of life (QoL) was observed favouring the inside-out approach. Two meta-analyses [5] and [6] and a Cochrane review of MUS [7] have reached similar conclusions, but they have all stressed the importance of performing long-term follow-up for adequately conducted RCTs.

There is a gap in the literature on the mid- to long-term outcomes following TO-TVT, with the vast majority of published RCTs reporting outcomes only up to 1-yr follow-up. In the United Kingdom, the National Institute for Health and Clinical Excellence (NICE) Interventional Procedures Programme Methods Guide[8] gives urinary and faecal incontinence as exemplars where durable results from interventions are essential to those interventions being considered efficacious. The NICE clinical guideline on urinary incontinence (UI) emphasises the need to inform women of the lack of long-term outcomes data and the importance of directing future research to secure such information [8]. Costantini and Lazzeri [9] have recently emphasised “the timely need for long-term follow-up of RCTs in surgical treatment of female SUI if we are to know, not just wonder, the durability of our surgical procedures.”

In this study we aim to address this gap in the literature by presenting 3-yr outcomes of the two types of TO-TVT in women with SUI [4].

2. Methods

The E-TOT RCT is a single-blind prospective randomised study conducted in a tertiary urogynaecology unit in the United Kingdom and approved by the Glasgow Research Ethics Committee for long-term follow-up. The protocol was registered on www.clinicaltrials.gov. All women admitted for a TO-TVT as a sole procedure in the period from April 2005 to April 2007 were invited to participate in the study. TO-TVT was performed as originally described [2] and [3] using TVT-O (Ethicon Inc., Somerville, NJ, USA) for the inside-out and TOT-Aris (Coloplast Corp., Minneapolis, MN, USA) for the outside-in approach. Study participants were women with urodynamic SUI who had previously failed or declined pelvic floor muscle treatment. Women with urodynamic mixed UI, however, with a predominant SUI complaint, were included. Women with uncontrolled overactive bladder (OAB) symptoms on antimuscarinic treatment, concomitant prolapse (greater than stage 2 on the pelvic organ prolapse quantification examination), and/or concomitant surgery were excluded. Preoperative assessment included pelvic examination, urodynamic assessment, and completion of the Birmingham Bowel Urinary Symptom-22 questionnaire [10], King's Health Questionnaire (KHQ) [11], and Prolapse Incontinence Sexual Function Questionnaire (PISQ-12) [12].

The initial cohort included 341 women (Fig. 1). At 3-yr follow-up, we anticipated achieving a 68% response rate, similar to Ward and Hilton [13]. Assuming approximately 230 women would respond (115 from each arm) and a success rate of 75% for inside-out TVT-O (as reported by Angioli et al. [14]), this would enable us, with 80% power, to detect a 20% difference in the patient-reported success rates between the two groups. Women who withdrew from the study (n = 14), had a subsequent pregnancy (n = 1), received chemotherapy (n = 1), or prolapse surgery (n = 1) within the first postoperative year were excluded from this follow-up study. Women who received further continence surgery (n = 11) within the first year of follow-up were included in this follow-up study and classified as failures. The remaining 313 women were contacted by post between August 2008 and April 2010 (ie, a minimum 3-yr follow-up) to complete a postal questionnaire including symptom severity, QoL, and sexual function questionnaires. In addition, women completed the Patient Global Impression of Improvement (PGI-I) [15], International Consultation of Incontinence Questionnaire-Short Form (ICIQ-SF) [16], and questions regarding any further treatment they may have received whether conservative, medical, or surgical. This assessment was previously performed at 1-yr follow-up [4].

Fig. 1 Consolidated Standards of Reporting Trials flowchart of patient recruitment and follow-up. TVT-O = Tension-free Vaginal Tape Obturator System (Ethicon Inc., Somerville, NJ, USA); TOT-Aris = Transvaginal Obturator Tape - Aris (Coloplast Corp., Minneapolis, MN, USA).

The primary outcome measure at 3 yr was the patient-reported success rate defined as very much improved/much improved on the PGI-I, while any other response (improved, same, worse, or much worse) were considered as failures. Secondary outcomes included patient-reported success on ICIQ-SF, defined as never leak/leak once or less per week; patient satisfaction, defined as a score ≥8 on a 10-point visual analogue scale; further surgical treatment for SUI; improvement in women's QoL (≥10 points improvement on the total KHQ score); improvement in sexual function (PISQ-12 scores); and late complications (ie, new or persistent after the first year of follow-up). Risk factors for late-failures of TO-TVT were also assessed.

Categorical variables were compared between treatment groups using the chi-square or Fisher exact test as appropriate. The distribution of continuous variables was assessed using Kolmogorov-Smirnov/Shapiro-Wilk tests where indicated and histograms were plotted. Within-group comparison of quantitative variables was undertaken using the Wilcoxon matched-pairs test; the Mann-Whitney test was used to compare outcomes between groups. The McNemar test was used to compare success rates at 1- versus 3-yr follow-up. A univariate analysis was used to assess risk factors associated with late failure based on the PGI-I outcome. Statistically and clinically significant factors were entered into a multivariable logistic regression model and independent risk factors identified. All statistical analysis was undertaken using SPSS v.18.0 (IBM Corp., Armonk, NY, USA).

3. Results

The 3-yr follow-up was completed by 238 of the 341 women (70%) (inside-out approach: n = 126; outside-in approach: n = 112) and forms the basis of this report. Figure 1 shows a Consolidated Standards of Reporting Trials flowchart. Twenty-two women (6%) underwent further surgical treatment for SUI (11 within the first year and a further 11 between 1 and 3 yr) and are included in this analysis as failures.

4. Discussion

Previously published reports lack data on long-term outcomes for TO-TVT. Five RCTs, including the E-TOT study, compared inside-out and outside-in TO-TVT, with follow-up ranging from 3 to 12 mo [4], [18], [19], [20], and [21]. Meta-analyses of these RCTs showed no evidence of significant differences in patient-reported or objective success rates and safety profiles of the two procedures [5], [6], and [7]. The authors concluded that the long-term efficacy and late adverse events of TO-TVT are yet to be determined [5], [6], and [7]. Three small RCTs have previously assessed the mid- to long-term outcomes of TOTs within one arm of their comparative groups (compared with RP-TVT) with different prespecified primary outcome measures [14], [22], and [23].

The patient response rate in our RCT was 70%. This was comparable with our preoperative assumption and the response rate of Ward and Hilton's RCT in a similar cohort of women [13] but significantly lower than reported by Angioli et al. [14], who had a limited cohort of 70 women. The E-TOT RCT showed a 73% patient-reported success rate and 70% satisfaction rate for TO-TVT, with modest differences between the inside-out and outside-in approaches that did not reach statistical significance. This is significantly lower than the 81% success rate reported for this same cohort at 1 yr, indicating a significant deterioration over time. Angioli et al. previously assessed the long-term outcomes of the inside-out TO-TVT and showed a similar 73% objective success rate and 62% satisfaction rate in 37 patients at 5 yr [14]. Similarly, Basseller et al. showed a 69.5% patient-reported success rate in women who underwent TO-TVT (n = 35) at 4-yr follow-up compared with 64.3% for the RP-TVT group [22]. Lipais et al, however, assessed 74 women who underwent inside-out TO-TVT in a nonrandomised study and 4-yr follow-up; they reported 81% patient-reported success and an 82.4% objective cure rate [24]. They failed, however, to use any validated questionnaires to assess patient-reported success rates. Furthermore, the pad test they used for objective assessment has been reported to overestimate success rates following surgical treatment of SUI [25].

In the E-TOT RCT, the reoperation rate was 6%; however, 50% of these procedures were performed prior to the 1-yr follow-up. Similarly, Angioli et al. reported that most of their failures occurred in the first year; however, a considerably higher proportion (14%) underwent further surgery in their study [14]. The highest reoperation rate was reported by Schierlitz et al. (20% within 3 yr) for women who underwent TO-TVT (n = 75) compared with 1.4% in the RP-TVT group [23]. Interestingly, in the latter study, there were no significant differences between both groups in QoL changes or patient-reported outcomes. A major limitation in the latter study was the failure to exclude women with concomitant prolapse repair or using it as a minimising covariant at randomisation, leading to significant heterogeneity in the results.

In our current clinical practice, women with failed TO-TVT and requiring further continence surgery would be offered repeat MUS (either RP-TVT or the other approach of TO-TVT); however, women with more than one previous failed continence surgery would be offered a rectus fascial sling or periurethral bulking agents. In our study, RP-TVT as a repeat MUS was successful in 10 of 11 women, while inside-out TVT-O was successful in seven of eight women; one woman in each group, with cured SUI, was still bothered by OAB symptoms. Four of five women with more than one previous failed continence surgery underwent rectus fascial sling, and SUI was cured in 50%. Our results are comparable with Biggs et al. [26] and Liapis et al. [27], who previously assessed inside-out TO-TVT and RP-TVT after previous failed MUS, and reported success rates of 81% and 71%, respectively. Multivariate analysis did not show any independent risk factors for late failure of TO-TVT; our analysis at 1-yr follow-up showed previous continence surgery and low urethral-closure pressure to be independent risk factors for failure [4]; however, this was not replicated for late failures.

In the E-TOT RCT, the complication rate at 3 yr was relatively low compared with Angioli et al. [14], who reported a 16% late-complication rate in TO-TVT; the retropubic TVT late-complication rate, however, was similar to Liapis et al. [24]. This was mainly due to the variety of definitions and types of complications included in all three studies; furthermore, asymptomatic vaginal erosions were undetected in our RCT.

QoL and sexual function are quite complicated to assess at longer term follow-up despite using disease-specific questionnaires, as many other confounding factors may have developed in patients’ lives that would inevitably affect their postoperative scores. Similar to our 1-yr results, 80% of women showed >10-point improvement in KHQ scores at 3 yr with no difference between both TO-TVT groups. Kheller et al. [28] have previously shown that a 10-point improvement is the minimum requirement for clinical relevance, although we recently reported a new minimum cut-off value of 18 points [17]. Repeating the analysis using the new cut-off value did not show any significant difference in QoL improvement between the groups. Although most of the women in the E-TOT RCT showed an improvement in sexual function scores at 3-yr follow-up, 21% reported deterioration in scores compared with 4.3% at 1-yr follow-up. However, this apparently significant deterioration should be interpreted with caution as several confounding factors, such as development of prolapse and menopausal vaginal dryness, may have affected these results. PISQ-12 assesses different aspects of sexual life, such as frequency of intercourse, orgasm, dyspareunia, and partner-related issues, but it is not validated for per-item analysis. Angioli et al. did not use any validated questionnaires to assess sexual function; however, they reported dyspareunia and coital incontinence in their late complications (5% in inside-out TO-TVT compared with 10% in RP-TVT) [14]. Several studies have previously assessed sexual function following MUS with ≤1-yr follow-up. The majority [29], [30], [31], and [32] suggest an overall improvement in sexual function after surgery, whereas two articles [33] and [34] reported no significant difference after surgery and another two articles [35] and [36] found that more women experienced worsening of symptoms than improvement.

The E-TOT RCT has number of strengths. It is adequately powered, with robust inclusion and exclusion criteria and standardised postoperative assessment using validated tools. The 3-yr follow-up was performed by postal questionnaire; effectively excluding any assessor bias and avoiding any extra hospital visits. The study centre is the only urogynaecologic regional referral centre in the area; therefore, it is unlikely that women lost to follow-up were referred to another unit for management of complications or recurrence. The single-centre RCT design can be a limitation, however, in the E-TOT RCT. Five consultant surgeons recruited the patients and performed the surgical procedures; therefore, we believe the results can be generalised to all surgeons who have completed their learning curve for TO-TVT. The lack of objective assessment for cure is a limitation of this study; however, the research community is increasingly recognising that patient-reported outcomes may be more clinically relevant. Furthermore, we presented the rates of further treatment received as an additional objective assessment of treatment efficacy. Another potential limitation in this RCT is the relatively high rate of patients lost to follow-up (30%). We presented a sensitivity analysis with different assumptions in an attempt to address this limitation.

5. Conclusions

The E-TOT RCT showed a 73% patient-reported success rate for TO-TVT at 3-yr follow-up in surgical treatment of female SUI, with no significant differences between both surgical approaches: inside-out and outside-in. There was a significant drop in the patient-reported success rates between 1- and 3-yr follow-up; however, no independent risk factor was found to be associated with these late failures. A repeat midurethral sling seems an effective surgical option when further continence surgery is required after failed TO-TVT.

Author contributions: Mohamed Abdel-fattah had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Abdel-fattah, Ramsay.

Acquisition of data: Abdel-fattah, Ramsay.

Analysis and interpretation of data: Familusi, Mostafa.

Drafting of the manuscript: Abdel-fattah, Mostafa, N’Dow.

Critical revision of the manuscript for important intellectual content: Abdel-fattah, Ramsay, Familusi, Mostafa, N’Dow.

Statistical analysis: Familusi, Mostafa.

Obtaining funding: Abdel-fattah, Ramsay.

Administrative, technical, or material support: Familusi, Mostafa.

Supervision: None.

Other (specify): None.

Financial disclosures: Mohamed Abdel-fattah certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: All authors of this paper have received travel grants from different pharmaceutical companies to attend medical conferences.

Funding/Support and role of the sponsor: This study was funded by the Henry Smith Charity.