european urology 52 (2007)

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1 european urology 52 (2007) available at journal homepage: Review Incontinence Tension-Free Midurethral Slings in the Treatment of Female Stress Urinary Incontinence: A Systematic Review and Meta-analysis of Randomized Controlled Trials of Effectiveness Giacomo Novara a,b, Vincenzo Ficarra a, Rafael Boscolo-Berto a, Silvia Secco a, Stefano Cavalleri a, Walter Artibani a, * a Department of Oncological and Surgical Sciences, Urology Clinic, University of Padua, Padua, Italy b I.R.C.C.S. Istituto Oncologico Veneto (IOV), Padua, Italy Article info Article history: Accepted June 11, 2007 Published online ahead of print on June 21, 2007 Keywords: Burch colposuspension Monarc Pubovaginal sling SPARC Stress urinary incontinence Tension-free vaginal tape TOT Trans-obturator tape TVT TVT-O Abstract Objectives: To evaluate the efficacy of tension-free vaginal tape (TVT) compared with other surgical treatments for stress urinary incontinence (SUI) and with other tension-free midurethral slings. Methods: A systematic review of the literature was performed in January 2007 using MEDLINE, Embase, and Web of Science. The searches used both MeSH and free text protocols. Meta-analysis was conducted using the Review Manager software 4.2 (Cochrane Collaboration). Results: Our search identified 37 randomized controlled trials. According to the Jadad score, the quality of the evaluated studies was limited in most papers. TVT outperformed Burch colposuspension in terms of postoperative continence rates (odds ratio [OR] from 0.38 to 0.59, according to the different end points), whereas success rates were similar after TVT and pubovaginal slings. Comparing TVT to the other retropubic tension-free midurethral vaginal slings, TVT was more efficacious than both intravaginal slingplasty (IVS; OR = 0.47; p = 0.007) and suprapubic arc (SPARC; OR from 0.53 to 0.56 according to the different evaluated end points). Indeed, the available data suggest similar efficacy for retropubic and trans-obturator tapes both in terms of subjective (OR = 0.98; p = 0.92) and objective (OR = 0.81; p = 0.34) rates. Conclusions: Our meta-analysis showed that TVT outperformed Burch colposuspension; efficacies of TVT and pubovaginal sling were similar. TVT was more efficacious than IVS and SPARC, whereas retropubic and trans-obturator tapes showed overlapping rates. The poor quality of most of the studies, both in terms of methodologic and clinical parameters, limits the strengths of the recommendations derived by the meta-analysis. # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Department of Oncological and Surgical Sciences, Urology Clinic, University of Padua, Monoblocco Ospedaliero, IV Floor, Via Giustiniani 2, 35128, Padua, Italy. Tel ; Fax: address: walter.artibani@unipd.it (W. Artibani) /$ see back matter # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi: /j.eururo

2 664 european urology 52 (2007) Introduction Pelvic floor dysfunctions are a major health care problem, affecting millions of women throughout the world. One in every nine American women will undergo surgery for a pelvic floor disorder in her lifetime, with 30% of those women requiring additional surgical procedures for recurrence of the same condition [1]. Specifically, estimations from the United States suggest that annually 135,000 women have surgery for urinary incontinence and 200,000 for prolapse [2 4]. Moreover, it is thought that the demand for surgery for pelvic floor disorders will increase by 45% in the next 30 yr due to the demographic distribution of the population in the western world and the increasing prevalence of pelvic floor dysfunction with age [5]. To date, the pathophysiologic bases of stress urinary incontinence (SUI) have not been completely understood and several hypotheses have been suggested as well as several surgical treatments. Since the first reports from the Ulmsten group [6], tension-free vaginal tape (TVT), the first polypropylene midurethral sling put on the market, has become one the most commonly performed procedures worldwide due to the ease of performance and high success rates and, to date, several hundred thousand TVT procedures have been performed. Moreover, several devices have been introduced on the market to make the midurethral sling procedures even less invasive, including suprapubic arc (SPARC) sling, intravaginal slingplasty (IVS), transobturator slings, prepubic TVT, and so on [7]. The purposes of the present meta-analysis were to evaluate the efficacy of TVT compared with the other surgical treatments for SUI and to compare the performances of the different tension-free midurethral slings. 2. Materials and methods The systematic review of the literature was performed in January 2007 using MEDLINE, Embase, and Web of Science. The MEDLINE search used a complex search strategy including both Medical Subject Heading (MeSH) and free text protocols. Specifically, the MeSH search was conducted by combining the following terms retrieved from the MeSH browser provided by MEDLINE: Urinary Incontinence, Stress, and Suburethral Slings. Multiple free text searches were performed applying singularly the following terms through the fields title and abstract of the records: Urinar*incont*, TVT, Tension-free vaginal tape*, Tension-free vaginal sling*, Transobturator tape*, Trans-obturator sling*, TVT-obturator, TVT-O, TOT, suprapubic arc sling*, SPARC sling*, intravaginal slingplasty, IVS sling, Uratape, ObTAPE, Prepubic sling*, Prepubic TVT, Prepubic tape*, PelviLace, Ureter, Aris, In-Fast, Monarc, I-Stop, and BioArc. Subsequently, the searches were pooled and the following limits were used: humans, gender (female), and language (English). No temporal limits were used. The searches on Embase and Web of Science used only the free-text protocol, with the same key words. Subsequently, the queries were pooled without applying any limits. In addition, other significant studies cited in the reference lists of the selected papers were considered. A total of 471 records were retrieved by searching MEDLINE, 399 in Embase, and 384 in Web of Science. Three of the authors reviewed their full texts to select the papers relevant to the review topic. Specifically, all the studies including outcomes of tension-free midurethral slings ( rates, satisfaction rates) were selected. Two authors collected separately the data from the studies in an electronic database, and another author verified the accuracy of data extraction and collection. The selected papers were distinguished according to the grade of evidence: meta-analyses of randomized controlled trials (RCTs) constitute the highest evidence (level 1a), followed by an adequately sampled single RCT (level 1b), systematic review of cohort studies (level 2a), and low-quality RCT or observational studies (level 2b). Lower grade of evidence was provided by surgical series (level 4) [8]. For the purpose of the present review, our attention was focused only on RCTs. The quality of the retrieved RCTs was assessed through the Jadad score [9]. A numerical score between 0 and 5 was assigned as a rough measure of study design and reporting quality, 0 being the weakest and 5 the strongest. One point was assigned if the trial was either randomized or double-blinded or in the case of an accurate description of the drop-out patients. Moreover, further points were given if randomization and blinding procedures were appropriate, whereas, instead, points were subtracted in the case of inappropriate descriptions of the same procedures. An overall score 3 indicated a good quality study [9]. To evaluate the efficacy of the different procedures, both objective (stress test, pad test) and subjective criteria (patients perception of the clinical improvement, expressed by validated questionnaires, institutional questionnaires, or open interview) were considered, reporting objective and subjective rates. In case of papers reporting patient outcome through the use of mixed subjective and objective end points (eg, no referred leakage and negative stress test, no referred leakage and negative pad test), an overall success rate was shown. Meta-analysis was conducted using the Review Manager software version 4.2 (The Cochrane Collaboration, Oxford, United Kingdom). Specifically, statistical heterogeneity was tested through the x 2 test. A p < 0.10 was used to indicate heterogeneity. In case of lack of heterogeneity, fixed-effects models were used for the meta-analyses. For the dichotomous data, results of each study were expressed as an odds ratio (OR) with a 95% confidence interval (CI). The presence of publication bias was evaluated through funnel plot, which is scatter plots of the treatment effect estimated by individual studies versus a measure of study size or precision. In this graphical representation, larger and more

3 european urology 52 (2007) precise studies are plotted at the top, near the combined effect size, and smaller and less precise studies will show a wider distribution below. If there is no publication bias, the studies would be expected to be symmetrically distributed on both sides of the combined effect size line. In case of publication bias, the funnel plot may be asymmetrical because the absence of studies would distort the distribution on the scatter plot [10]. 3. Results Once we excluded duplicate publications, papers evaluating technical variants of the classical TVT procedure, studies evaluating the treatment of persistent SUI after TVT procedure, and those including only urodynamic data, 169 studies were selected. Among these, we identified 31 RCTs [11 41]. Six further RCTs were identified from the reference lists of the retrieved papers [42 48]. Among these studies, 30 were full text publications [11 28,30 32,34 41], and 8 RCTs were published as congress abstracts only [29,33,42 48] RCTs comparing retropubic tension-free midurethral tapes to Burch colposuspension To date, nine RCTs compared TVT to Burch colposuspension as primary treatment for SUI [15,20,23,30,31,36,37,39,40]. A further study compared SPARC to laparoscopic Burch colposuspension [22] (Table 1). Ward and Hilton, on behalf of the United Kingdom and Ireland Tension-free Vaginal Tape Trial Group, were the first to report on 344 patients with SUI, who were randomized to TVT or Burch colposuspension. The trial was very well designed and performed, including both subjective and objective end points, as well as the use of generic (Rand SF-36) and disease-specific (Bristol Female Lower Urinary Tract Symptoms [BFLUTS]) questionnaires to assess symptoms and the impact of the surgical treatment on health-related quality of life. At a 2-yr follow-up reported in a subsequent publication [40], a negative 1-h pad test was recorded in 81% of the patients who had undergone TVT and in 80% of those in the Burch group. In two sensitivity analyses performed to deal with the patients lost to follow-up, TVT slightly outperformed colposuspension. Using the BFLUTS, only 25% of the women in the TVT arm and 20% of those in the colposuspension group reported no urine leakage under any circumstance. Along the followup, indeed, the patients in the colposuspension arm reported worse health-related quality of life, as expressed by SF-36 scores, in emotional, social, and physical function and vitality domains at the 6-wk follow-up, emotional and social functioning, vitality, and mental health domains at 6-mo follow-up, and in role limitation because of emotional problems and mental health at 24-mo follow-up [40]. The study should be regarded as a high-quality trial despite the lack of blinding procedures because of appropriate randomization technique, accurate selection of outcomes, and subjective and objective tools to evaluate the patients (Jadad score 3). The data at 2-yr follow-up, however, are not sufficient and long-term results are still awaited. Similar efficacy between TVT and Burch colposuspension was also reported by Liapis el al [23], Bai et al [15], and El-Barky et al [20], although all the trials included few patients and were methodologically less solid. Interestingly, Valpas et al published a well-performed trial comparing TVT and laparoscopic Burch colposuspension, in which both subjective and objective criteria (stress test and 48-h pad test) were used to evaluate the rate. At the 1-yr follow-up, patients in the TVT arm significantly outperformed those in the laparoscopic colposuspension group both in terms of objective rate (negative stress test: 85.7% vs. 56.9%; p < ) and in the subjects personal perception of the result of the procedures, as evaluated by King s Health Questionnaire scores [37]. Despite short follow-up and the lack of blinding procedures, the study is a high-quality RCT because of appropriate randomization technique, accurate selection of outcomes, and subjective and objective tools to evaluate the patients (Jadad score 3). Similar data, however, were not reconfirmed by Persson et al [31], Ustun et al [36], and Paraiso et al [30]. Fig. 1 shows the forest plots concerning the metaanalyses of rates according to different definitions. TVT was followed by significantly higher continence rates compared to Burch colposuspension, considering success rates evaluated according to any definition of continence (OR = 0.58; 95%CI OR = ; p = ; Fig. 1a), presence of negative stress test (OR = 0.38; 95%CI OR = ; p < ; Fig. 1b), and negative pad test (OR = 0.59; 95%CI OR = ; p = 0.005; Fig. 1c). A further RCT compared another retropubic tape, the SPARC sling, to laparoscopic colposuspension [22]. The inclusion of this study in all the metaanalyses did not significantly modify the figures reported above (forest plots not shown). Further sensitivity analyses limited to the RCTs with followup >12 mo or evaluating laparoscopic colposuspension provided results similar to those reported above (forest plots not shown).

4 666 Table 1 Randomized controlled trials comparing retropubic tension-free midurethral slings to Burch colposuspension as primary treatment for stress urinary incontinence: subjective, objective, and overall rates Reference Cases Follow-up, mo of overall Overall rate of objective Objective rate of subjective Subjective rate Level Jaded of score evidence Liapis 2002 [23] TVT NR 84% NR NR NR NR 2b 0 Colposuspension 35 86% Persson 2002 [31] TVT NR NR Negative pad test 89% Dry at nonvalidated 57% 2b 2 Lap. colposuspension 32 87% 52% questionnaire Ward 2002 [39] * TVT NR NR Negative 1-h pad test/ 73%/81%/66% BFLUTS Q4, 6-9/ 36%/59% 1b 3 Colposuspension 169 negative stress test/ 64%/67%/57% BFLUTS Q7 28%/53% both negative Ustun 2003 [36] TVT No referred leak at 82.6% NR NR NR NR 2b 0 Lap. colposuspension interview, negative 82.6% stress test, no urodynamic SUI Paraiso 2004 [30] TVT NR NR Negative stress test 96.8% NR NR 1b 3 Lap. colposuspension % Valpas 2004 [37] TVT NR NR Negative stress test/ 85.7%/72.9% King s College Favor TVT 1b 3 Lap. colposuspension 51 negative 48-h pad test 56.9%/58.8% Health Questionnaire Ward 2004 [40] * TVT NR NR Negative 1-h pad test 63% BFLUTS Q4, 6-9/ 25%/43% 1b 3 Colposuspension % BFLUTS Q7 20%/37% Bai 2005 [15] TVT No referred 87% NR NR NR NR 2b 0 Colposuspension 33 leakage at interview 87.8% and negative stress test El-Barky 2005 [20] TVT Not reported 72% NR NR NR NR 2b 0 Colposuspension 25 72% Foote 2006 [22] SPARC No leak and VAS < % NR NR NR NR 2b 0 Lap. colposuspension % european urology 52 (2007) TVT = tension-free vaginal tape; NR = not reported; lap. = laparoscopic; BFLUTS = Bristol Female Lower Urinary Tract Symptoms; SUI = stress urinary incontinence; SPARC = suprapubic arc; VAS = visual analog scale. * Same randomized controlled trial, published at different follow-ups.

5 european urology 52 (2007) Fig. 1 Forest plots of continence rates after TVT and Burch colposuspension: 1a: continence rate according to any definition of ; 1b: continence rate according to the presence of negative stress test; 1c: continence rate according to the presence of negative pad test RCTs comparing TVT to pubovaginal slings Five RCTs compared TVT to pubovaginal sling as primary treatment for SUI (Table 2) [11,12,14,15,38]. Three studies compared the efficacy of TVT to autologous slings [12,15,38], although all the RCTs were small, low-quality studies. Bai et al found that rectal fascia pubovaginal sling outperformed both TVT and Burch colposuspension, with 92.8% of the patients being d at the 12-mo follow-up (compared to 87.8% the Burch colposuspension group and 87% of the TVT patients) [15]. Similar continence rates between TVT and pubovaginal sling were reported in the study by Wadie et al (92% after TVT and 92.9% after sling) [38] and Amaro et al [12]. Arunkalaivanan et al reported data on 132 patients randomized to TVT (68 cases) or porcine dermal sling (Pelvicol TM implant, Bard; 74 cases), using a nonvalidated questionnaire to assess the outcome. At the 12-mo follow-up, 85.3% of those patients undergoing TVT and 89.2% of those after Pelvicol implant subjectively reported to be dry [14]. The same group published data at a 36-mo follow-up, reporting rates, with patients lost to follow-up considered as

6 Table 2 Randomized controlled trials comparing TVT to pubovaginal sling as primary treatment for stress urinary incontinence: subjective, objective, and overall rates 668 Reference Cases Follow-up, mo of overall Overall rate of objective Objective rate of subjective Subjective rate Level of evidence Jaded score Arunkalaivanan 2003 [14] * TVT NR NR NR NR Dry at non-validated 85.3% 1b 3 Pelvicol 74 questionnaire 89.2% Abdel-Fattah 2004 [11] * TVT NR NR NR NR Dry at non-validated 77.8% 1b 3 Pelvicol 74 questionnaire 79.1% Bai 2005 [15] TVT No referred leakage 87% NR NR NR NR 2b 0 Rectus fascia at interview and 92.8% sling 28 negative stress test Wadie 2005 [38] TVT 25 6 No pads and 92% NR NR NR NR 2b 0 Rectus fascia sling 28 negative stress test 92.9% Amaro 2007 [12] TVT NR 65% NR NR NR NR 2b 0 Autologous sling 21 57% TVT = tension-free vaginal tape; NR = not reported. * Same randomized controlled trial, published at different follow-ups. Table 3 Randomized controlled trials comparing TVT to IVS as primary treatment for stress urinary incontinence: subjective, objective, and overall rates Reference Cases Follow-up, mo of overall Overall rate of objective Objective rate of subjective Subjective rate Level of evidence Jaded score european urology 52 (2007) Rechberger 2003 [32] TVT No referred leakage 88% NR NR NR NR 2b 1 IVS 50 at interview and 80% NR negative cough test Lim 2005 [25] TVT NR NR Negative stress test 87.9% No referred leakage 78.7% 2b 1 IVS % at interview 78.3% Meschia 2006 [28] TVT NR NR Negative 1-h pad 85%/86% No referred leakage 87% 2b 2 IVS 95 test/negative cough test 72%/75% at interview 78% TVT = tension-free vaginal tape; IVS = intravaginal slingplasty; NR = not reported.

7 european urology 52 (2007) Fig. 2 Forest plots of continence rates after TVT and pubovaginal sling: 2a: continence rate according to any definition of in all the 4 RCTs; 2b: continence rate according to any definition of in the RCTs evaluating only autologous sling. failures, as high as 77.8% and 79.1%, respectively [11]. In both arms of the studies, no major complications occurred, and the percentages of minor complications were slightly higher in the Pelvicol group. At follow-up, few patients needed clean intermittent self-catheterization for voiding lower urinary tract symptoms (3.4% after TVT and 1.4% after Pelvicol), sling releasing being performed in 2.9% of the patients who had undergone TVT and 6.8% of the Pelvicol group [11,14]. Both the RCTs are low-quality studies, due to the lack of blinding procedures, inappropriate randomization technique (Jadad score 1), and use of a non-validated questionnaire to assess the outcome. Fig. 2 shows the forest plots concerning the metaanalyses of rates. TVT and pubovaginal slings showed similar continence rates, evaluated according to any definition of continence (OR = 0.82; 95%CI OR = ; p = 0.55; Fig. 2a). The same results were obtained considering only autologous slings (OR = 1.03; 95%CI OR = ; p = 0.94; Fig. 2b). Further sensitivity analyses limited to the RCTs with follow-up >12 mo did not significantly modify the figures reported above (forest plots not shown). A further RCT compared TVT and endopelvic fascia plication in patients with occult SUI undergoing surgery for pelvic organ prolapse [27]. Fifty patients with anterior vaginal wall prolapse undergoing vaginal hysterectomy, McCall culdoplasty, and cystocele repair were randomized to concomitant TVT or endopelvic fascia plication at the level of the urethrovesical junction. At a median followup of 24 wk, SUI was less common after TVT, considering both subjective (4% vs. 36%, p = 0.01) and objective (8% vs. 44%, p = 0.01) criteria [27] RCTS comparing TVT to other retropubic tension-free midurethral slings Three RCTs compared TVT to IVS, a midurethral sling produced by Tyco, designed to be implanted in the retropubic space downside-to-top, as primary treatment for SUI (Table 3) [25,28,32]. The main difference between the two devices is determined by the texture of the polypropylene fibers constituting the mesh, with IVS being multifilament, having a denser texture and smaller pores (55 65 mm), resulting in a more rigid mesh [49]. Rechberger et al were the first to report an RCT in which classical TVT was compared to an IVS device. Specifically, the study included 50 patients in each arm and used mixed subjective and objective criteria (no referred leakage of urine and negative cough

8 670 european urology 52 (2007) Fig. 3 Forest plots of continence rates after TVT and IVS: 3a: continence rate according to the presence of negative stress test; 3b: continence rate according to the subjective criteria; 3c: continence rate according to any definition of. test) to define success after surgery. At a median follow-up of 13.5 mo, rate was slightly higher in the TVT arm (88% vs. 80%). Complication rates were similar, with the exception of postoperative acute urinary retention, which was significantly more common among the patients who had TVT placement [32]. The study should be considered a poorquality RCT due to the lack of appropriate randomization and blinding procedures (Jadad score 1). The largest trial was recently published by Meschia et al, who reported data on 190 patients randomized 1:1 to TVT or IVS. The study was quite well designed, using both objective and subjective criteria to define postoperative continence and presented an acceptable 24-mo follow-up. Considering all the cases lost to follow-up as failures, the study finally showed significantly higher continence rates for the patients treated with TVT, regardless of the applied definition of continence [28]. Fig. 3 shows the forest plots concerning the metaanalyses of rates. TVT outperformed IVS, considering success rates evaluated according to any definition of continence (OR = 0.51; 95%CI OR = ; p =0.007; Fig. 3c), and presence of negative stress test (OR = 0.47; 95%CI OR = ; p = 0.007; Fig. 3a), whereas the subjective rates were similar (OR = 0.63; 95%CI OR = ; p = 0.10; Fig. 3b). Further sensitivity analyses limited to the RCTs with a follow-up >12 mo reconfirmed similar figures (forest plots not shown). Four RCTs compared TVT to SPARC, a sling produced by AMS and developed to be implanted topside-to-down, as primary treatment for SUI (Table 4) [13,25,26,35].

9 european urology 52 (2007) Fig. 4 Forest plots of continence rates after TVT and Sparc: 4a: continence rate according to the presence of negative pad test; 4b: continence rate according to the to the presence of negative stress/cough test; 4c: continence rate according to any objective criteria; 4d: continence rate according to subjective criteria. In the study with the longest median follow-up (25 mo), Tseng et al compared the efficacy and complication rates of TVT and SPARC in 62 patients, using a negative 1-h pad test to define postoperative continence. Specifically, the authors reported similar continence rates in the two arms (87.1% vs. 80.7%) and similar complication rates in all the assessable parameters [35]. The study is a goodquality RCT (Jadad score 3). Similar figures were reported by Andonian et al [13] and Lim et al [25].

10 672 european urology 52 (2007) Table 4 Randomized controlled trials comparing TVT to SPARC as primary treatment for stress urinary incontinence: subjective, objective, and overall rates Jaded score Level of evidence Subjective rate of subjective Objective rate of objective Reference Cases Follow-up, mo Andonian 2005 [13] TVT Negative 1-h pad test 95% IIQ score Non-significant 2b 2 SPARC 41 83% difference Lim 2005 [25] TVT Negative stress test 87.9% No referred leakage 78.7% 2b 1 SPARC % at interview 75% Tseng 2005 [35] TVT Negative pad test 87.1% NR NR 1b 3 SPARC % Lord 2006 [26] TVT Negative cough test 97.3% No use of protection 87.1% 1b 3 SPARC % 76.5% TVT = tension-free vaginal tape; SPARC = suprapubic arc; IIQ = Incontinence Impact Questionnaire; NR = not reported. However, in the largest published RCT, enrolling 147 patients randomized to TVT and 154 to SPARC, Lord et al showed significantly higher subjective continence rates in the TVT arm (87.1% vs. 76.5%; p = 0.03), although the short follow-up (6 8 wk) limits the salience of these figures [26]. Despite the currently available inadequate follow-up duration, the trial was methodologically accurate (Jadad score 3). Fig. 4 shows the forest plots concerning the metaanalyses of rates. With regard to continence rates, TVT outperformed SPARC in terms of subjective rate (OR = 0.56; 95%CI OR = ; p = 0.02; Fig. 4d), and objective rates according to any definition (negative stress test, negative cough test, negative pad test; OR = 0.53; 95%CI OR = ; p = 0.005; Fig. 4c) and presence of negative stress or cough tests (OR = 0.56; 95%CI OR = ; p = 0.02; Fig. 4b). The data of the comparisons were significantly influenced by the data from the study of Lord et al [26], which enrolled about 50% of the analyzed patients and evaluated them at a 2-mo follow-up only. Excluding this RCT, only a nonstatistically significant trend in favor of TVT was identified considering objective rates (OR = 0.41; 95%CI OR = ; p = 0.09) RCTs comparing retropubic to trans-obturator tension-free midurethral slings Excluding the paper by DeTayrac et al, which was retracted for major violation of the ethical standards for conducting human research [19], seven trials compared Gynecare TVT and Gynecare TVT- O (a macroporous polypropylene mesh, to be inserted inside-to-out through the obturator foramen) [24,33,41]; three RCTs compared Gynecare TVT to different trans-obturator tapes (TOTs; meshes to be inserted outside-to-in through the obturator foramen) [43,46,47], and a further study compared TVT to Monarc, a knitted macroporous polypropylene mesh produced by AMS, to be placed outside-to-in through the trans-obturator route [21]; a single study compared SPARC to Monarc [29]; two further RCTs reported on a series of patients where I-Stop, a macroporous monofilament polypropylene mesh produced by CL Medical, was implanted through retropubic or trans-obturator route [16,17] (Table 5). With the exclusion of the recently published study by Zullo et al [41], all the studies were methodologically weak, due to inaccurate randomization and blinding procedures, were underpowered for most of the end points, had short follow-up

11 Table 5 Randomized controlled trials comparing retropubic to trans-obturator tapes as primary treatment for stress urinary incontinence: subjective, objective, and overall rates Reference Cases Follow-up, mo of overall Overall rate of objective Objective rate of subjective Subjective rate Level of evidence Jaded score Mansoor 2003 [43] TVT 54 NR NR 93% NR NR NR NR 2b 0 TOT 48 96% David-Montefiore 2005 [17] * Retropubic I-Stop 42 1 NR NR NR NR UDI 92.9% 2b 1 Trans-obturator 93.5% I-Stop 46 Enzelsberger 2005 [21] TVT NR NR Negative stress test 86% NR NR 2b 0 Monarc 56 and no urodynamic SUI 84% Na 2005 [29] SPARC 65 3 NR 86.2% NR NR NR NR 2b 1 Monarc % Porena 2005 [46] TVT NR NR NR 93.6% NR 70.2% 2b 1 TOT % 78.6% Ryu 2005 [33] TVT 40 NR NR NR NR NR I-QOL score Non-significant 2b 1 TVT-O 40 difference Laurikainen 2006 [42] TVT NR NR Negative stress test 98.5% VAS Non-significant 2b 0 TVT-O % difference Liapis 2006 [24] TVT NR NR Negative 1-h pad test 89% Non-validated 73.9% 2b 1 TVT-O 43 and negative cough test 90% questionnaire 76.7% Meschia 2006 [44] TVT NR NR Negative cough test 92% ICI-SF, W-IPSS, 92% 1b 3 TVT-O % PGI-S 87% Oliveira 2006 [45] TVT NR 100% NR NR NR NR 2b 0 TVT-O % Riva 2006 [47] TVT 66 >12 NR NR NR 89.4% NR 94% 2b 0 TOT % 91% Zhu 2006 [48] TVT NR NR NR NR NR 92.6% 2b 0 TVT-O % Darai 2007 [16] * Retropubic I-Stop NR NR NR NR UDI 88.5% 2b 1 Trans-obturator 86.5% I-Stop 46 Zullo 2007 [41] TVT NR NR Negative stress test 91% NR NR 1b 3 TVT-O 37 89% TVT = tension-free vaginal tape; TOT = trans-obturator tape; NR = not reported; UDI = Urinary Distress Inventory; SUI = stress urinary incontinence; TVT-O = TVT-obturator; I-QOL = Incontinence Quality of Life; VAS = visual analog scale; ICI-SF = International Consultation on Incontinence-Short Form; W-IPSS = Women International Prostate Symptom Score; PGI-S = Patient s Global Expression of Severity. * Same randomized controlled trial, published at different follow-ups. european urology 52 (2007)

12 674 european urology 52 (2007) Fig. 5 Forest plots of continence rates after retropubic or transobturator tapes: 5a: continence rate according to the objective criteria; 5b: continence rate according to subjective criteria; 5c: continence rate according to any definition of. durations, and some published only as congress abstracts [29,33,42 46,48]. In the best published RCT, Zullo et al randomized 70 patients to TVT or TVT-O. Using a negative stress test to define surgical success, the authors reported similar success rates in the two arms (91% vs. 89%) at a median follow-up of 16 mo [41]. Although the study has to be considered a good-quality RCT according to methodologic considerations (appropriate randomization procedure, blinding data collection, no patients lost to follow-up, Jadad score 3), it was powered to detect only differences in intraoperative and postoperative complication rates and the currently available follow-up is only modest. Although published only as congress abstract, Meschia et al reported at the 31st annual meeting of the International UroGynecological Association (IUGA) on a prospective randomized multicenter trial comparing TVT to TVT-O. Specifically, 114 patients were randomized to TVT and 117 to TVT-O, using both subjective and objective criteria to evaluate continence. At a 9-mo follow-up, similar continence rates were reported in

13 european urology 52 (2007) both arms [44]. Although published only as a congress abstract, the study has to be considered a goodquality RCT, according to both statistical and clinical consideration (Jadad score 3). Fig. 5 shows the forest plots concerning the metaanalyses of rates. Patients randomized to retropubic or trans-obturator tapes yielded similar postoperative objective (OR = 0.81; 95%CI OR = ; p = 0.34), subjective (OR = 0.98; 95%CI OR = ; p = 0.92), and overall (OR = 0.91; 95%CI OR = ; p = 0.81) continence rates (Fig. 5a c). Similar figures were obtained in sensitivity analyses considering only the studies available as full text publications on peer-reviewed journals (objective rate: OR = 0.89; 95%CI OR = ; p = 0.75; subjective rate OR = 1.06; 95%CI OR = ; p = 0.88); and only the studies with follow-up of at least 12 mo (objective rate: OR = 0.99; 95%CI OR = ; p = 0.98; subjective rate: OR = 1.06; 95%CI OR = ; p = 0.84). Two further RCTs compared TOTs to autologous pubovaginal slings showing lower efficacy for transobturator SAFYRE, a monofilament polypropylene mesh produced by Promedon [34] and two different TOTs (inside-to-out TVT-O and outside-to-in Monarc), reporting similar performances for both tapes [18]. Neither study was included in the metaanalysis. 4. Discussion Following the initial reports by Ulmsten on a new surgical procedure to treat SUI [6], the TVT, Gynaecare gained worldwide diffusion due both to mini-invasiveness and high success rates. With the aim of making sling procedures even less invasive,morecosteffective,and,sometimes,only for patent issues, other devices to be implanted retropubically, such as SPARC (AMS) sling, IVS sling, I-Stop, and others have been placed on the market. More recently, to reduce the risk of complications in the retropubic space, the trans-obturator route has been used for placing the sling, both with outside-in (Monarc, AMS; Obtape TM, Mentor-Porges; Obtryx TM, Boston Scientific; TOT, Uratape TM, Mentor-Porges) and inside-out approaches (TVT-O TM,Gynaecare). Although a meta-analysis comparing retropubic and trans-obturator tapes has been published recently [50], the present paper is the first to assess extensively the role of tension-free midurethral slings in SUI in comparison with the other surgical techniques for SUI. The data of our meta-analysis showed that TVT outperformed Burch colposuspension in terms of postoperative continence rates, whereas efficacies of TVT and pubovaginal slings were similar. In comparison to other tension-free midurethral slings, TVT was more efficacious than the other retropubic tapes available (IVS and SPARC). In comparison to TOTs, the available data suggest similar efficacy for retropubic and trans-obturator tapes. Further comparisons were not possible due to the heterogeneity of the available trials. According to the criteria of evidence-based medicine, meta-analyses of good-quality RCTs are considered the studies with the highest level of evidence (1a), providing grade A recommendations for the clinical decision-making processes. Despite the presence of some concerns about publication bias, our systematic review fulfilled most of the criteria of the Overview Quality Assessment Questionnaire (OQAQ) to be considered a good-quality review [51]. However, the overall value of the metaanalysis is impaired by several limitations of the studies included. Using a simple score to evaluate the quality of the RCTs, only 10 of the studies had a score 3, which indicates a methodologically good study [9]. However, using clinical criteria to evaluate the study, the figures are even weaker. Only seven RCTs used validated questionnaires to assess symptoms of urinary incontinence and their impact on quality of life [13,17,33,37,39,40,44], but seven different tools were applied (BFLUTS, King s College Health Questionnaire, International Consultation on Incontinence-Short Form, Incontinence Impact Questionnaire score, Incontinence Quality of Life score, Patient s Global Expression of Severity, and Urinary Distress Inventory), making comparisons impossible. Moreover, as regards criteria to define continence, 16 studies failed to report the criteria or used different mixed subjective and objective end points, which, again, made comparison difficult and inaccurate. Most importantly, almost all the RCTs had a mean follow-up that is insufficient to assess the long-term efficacy of surgical procedures for SUI (a single study reported data at follow-up as long as 36 mo) [11]. Consequently, most of the recommendations deriving from the present meta-analysis are not of grade A. Further high-quality RCTs, following the recommendations for the clinical research provided by the 3rd International Consultation on Incontinence are highly desirable, using standardized criteria to evaluate continence and success rates after surgery [52]. 5. Conclusions The figures of the published literature summarized in our meta-analysis showed that TVT outper-

14 676 european urology 52 (2007) formed Burch colposuspension both in terms of postoperative continence rates, whereas success rate efficacies were similar after TVT and pubovaginal slings. Comparing TVT to the other retropubic tension-free midurethral vaginal slings, TVT was more efficacious than both IVS and SPARC. The available data suggest similar efficacy for retropubic and trans-obturator tapes. Considering the overall quality of the trials included, both in terms of methodologic and clinical parameters, most of the studies were of limited quality, which limits the strengths of the recommendations derived by any meta-analysis. Conflicts of interest The authors have nothing to disclose. Acknowledgments The authors thank Drs. L. Cindolo, O. Dalpiaz, C. D Elia, J.L. Gutierrez Banos, X. Iglesias, and G. Valenza for the collaboration they offered during our work on this manuscript. References [1] Olsen AL, Smith VJ, Bergstrom JO, Colling JC, Clark AL. Epidemiology of surgically managed pelvic organ prolapse and urinary incontinence. Obstet Gynecol 1997;89: [2] Waetjen LE, Subak LL, Shen H, et al. Stress urinary incontinence surgery in the United States. Obstet Gynecol 2003;101: [3] Boyles SH, Weber AM, Meyn L. Procedures for pelvic organ prolapse in the United States, Am J Obstet Gynecol 2003;188: [4] Brown JS, Waetjen LE, Subak LL, Thom DH, Van den Eeden S, Vittinghoff E. Pelvic organ prolapse surgery in the United States, Am J Obstet Gynecol 2002;186: [5] Luber KM, Boero S, Choe JY. The demographics of pelvic floor disorders: current observations and future projections. Am J Obstet Gynecol 2001;184: [6] Ulmsten U, Henriksson L, Johnson P, Varhos G. An ambulatory surgical procedure under local anesthesia for treatment of female urinary incontinence. Int Urogynecol J 1996;7:81 6. [7] Bullock TL, Ghoniem G, Klutke CG, Staskin DR. Advances in female stress urinary incontinence: mid-urethral slings. BJU Int 2006;98(Suppl 1): [8] Phillips B, Ball C, Sackett D, et al. Levels of Evidence and Grades of Recommendation. Oxford Centre for Evidencebased Medicine downloaded at levels_of_evidence.asp. [9] Jadad AR. Randomised controlled trials. London, United Kingdom: BMJ Publishing Group; [10] Rothstein HR, Sutton AJ, Borenstein M. Publication bias in metaanalysis: prevention, assessment and adjustment. Chichester, United Kingdom: John Wiley; [11] Abdel-Fattah M, Barrington JW, Arunkalaivanan AS. Pelvicol TM pubovaginal sling versus tension-free vaginal tape for treatment of urodynamic stress incontinence: a prospective randomized three-year follow-up study. Eur Urol 2004;46: [12] Amaro JL, Yamamoto HA, Kawano PR, et al. A prospective randomized trial of autologous fascial sling (AFS) versus tension-free vaginal tape (TVT) for treatment of stress urinary incontinence (SUI). J Urol 2007;177(Suppl 4):482 (abstract no. 1460). [13] Andonian S, Chen T, St-Denis B, Corcos J. Randomized clinical trial comparing suprapubic arch sling (SPARC) and tension-free vaginal tape (TVT): one-year results. Eur Urol 2005;47: [14] Arunkalaivanan AS, Barrington JW. Randomized trial of porcine dermal sling (Pelvicol implant) vs. tension-free vaginal tape (TVT) in the surgical treatment of stress incontinence: a questionnaire-based study. Int Urogynecol J Pelvic Floor Dysfunct 2003;14: [15] Bai SW, Sohn WH, Chung DJ, Park JH, Kim SK. Comparison of the efficacy of Burch colposuspension, pubovaginal sling, and tension-free vaginal tape for stress urinary incontinence. Int J Gynaecol Obstet 2005;91: [16] Daraï E, Frobert J-L, Grisard-Anaf M, et al. Functional results after the suburethral sling procedure for urinary stress incontinence: a prospective randomized multicentre study comparing the retropubic and transobturator routes. Eur Urol 2007;51: [17] David-Montefiore E, Frobert J-L, Grisard-Anaf M, et al. Peri-operative complications and pain after the suburethral sling procedure for urinary stress incontinence: a French prospective randomised multicentre study comparing the retropubic and transobturator routes. Eur Urol 2006;49: [18] Debodinance P. Trans-obturator urethral sling for surgical correction of female stress urinary incontinence: outsidein (Monarc) versus inside-out (TVT-O). Are both ways safe? J Gynecol Obstet Biol Reprod 2006;35: [19] detayrac R, Deffieux X, Droupy S, Chauveaud-Lambling A, Calvanese-Benamour L, Fernandez H. A prospective randomized trial comparing tension-free vaginal tape and transobturator suburethral tape for surgical treatment of stress urinary incontinence. Am J Obstet Gynecol 2004; 190: [20] El-Barky E, El-Shazly A, El-Wahab OA, Kehinde EO, Al- Hunayan A, Al-Awadi KA. Tension free vaginal tape versus Burch colposuspension for treatment of female stress urinary incontinence. Int Urol Nephrol 2005;37: [21] Enzelsberger H, Schalupny J, Heider R, et al. TVT versus TOT a prospective randomized study for the treatment of female stress urinary incontinence at a follow-up of 1 year. Geburtshilfe Frauenheilkd 2005;65: [22] Foote AJ, Maughan V, Carne C. Laparoscopic colposuspension versus vaginal suburethral slingplasty: a randomised

15 european urology 52 (2007) prospective trial. Aust N Z J Obstet Gynaecol 2006;46: [23] Liapis A, Bakas P, Creatsas G. Burch colposuspension and tension-free vaginal tape in the management of stress urinary incontinence in women. Eur Urol 2002;41: [24] Liapis A, Bakas P, Giner M, Creatsas G. Tension-free vaginal tape versus tension-free vaginal tape obturator in women with stress urinary incontinence. Gynecol Obstet Invest 2006;62: [25] Lim YN, Muller R, Corstiaans A, Dietz HP, Barry C, Rane A. Suburethral slingplasty evaluation study in North Queensland, Australia: the SUSPEND trial. Aust N Z J Obstet Gynaecol 2005;45:52 9. [26] Lord HE, Taylor JD, Finn JC, et al. A randomized controlled equivalence trial of short-term complications and efficacy of tension-free vaginal tape and suprapubic urethral support sling for treating stress incontinence. BJU Int 2006;98: [27] Meschia M, Pifarotti P, Spennacchio M, Buonaguidi A, Gattei U, Somigliana E. A randomized comparison of tension-free vaginal tape and endopelvic fascia plication in women with genital prolapse and occult stress urinary incontinence. Am J Obstet Gynecol 2004;190: [28] Meschia M, Pifarotti P, Bernasconi F, et al. Tension-free vaginal tape (TVT) and intravaginal slingplasty (IVS) for stress urinary incontinence: a multicenter randomized trial. Am J Obstet Gynecol 2006;195: [29] Na YG, Roh AS, Youk SM, et al. A prospective multicentre randomized study comparing transvaginal tapes (Sparc sling system) and transobturator suburethral tapes (Monarc sling system) for thesurgical treatment of stress urinary incontinence. Eur Urol Suppl 2005;4(3):15 (abstract no. 49). [30] Paraiso MF, Walters MD, Karram MM, Barber MD. Laparoscopic Burch colposuspension versus tension-free vaginal tape: a randomized trial. Obstet Gynecol 2004;104: [31] Persson J, Teleman P, Eten-Bergquist C, Wolner-Hanssen P. Cost-analyzes based on a prospective, randomized study comparing laparoscopic colposuspension with a tension-free vaginal tape procedure. Acta Obstet Gynecol Scand 2002;81: [32] Rechberger T, Rzezniczuk K, Skorupski P, et al. A randomized comparison between monofilament and multifilament tapes for stress incontinence surgery. Int Urogynecol J Pelvic Floor Dysfunct 2003;14: [33] Ryu KH, Shin JS, Du JK, Choo MS, Lee KS. Randomized trial of tension-free vaginal tape (TVT) vs. tension-free vaginal, tape obturator (TVT-O) in the surgical treatment of stress urinary incontinence: comparison of operation related morbidity. Eur Urol Suppl 2005;4(3):15 (abstract no. 50). [34] Silva-Filho AL, Candido EB, Noronha A, Triginelli SA. Comparative study of autologous pubovaginal sling and synthetic transobturator (TOT) SAFYRE sling in the treatment of stress urinary incontinence. Arch Gynecol Obstet 2006;273: [35] Tseng LH, Wang AC, Lin YH, Li SJ, Ko YJ. Randomized comparison of the suprapubic arc sling procedure vs tension-free vaginal taping for stress incontinent women. Int Urogynecol J Pelvic Floor Dysfunct 2005;16: [36] Ustun Y, Engin-Ustun Y, Gungor M, Tezcan S. Tensionfree vaginal tape compared with laparoscopic Burch urethropexy. J Am Assoc Gynecol Laparosc 2003;10: [37] Valpas A, Kivela A, Penttinen J, Kujansuu E, Haarala M, Nilsson CG. Tension-free vaginal tape and laparoscopic mesh colposuspension for stress urinary incontinence. Obstet Gynecol 2004;104:42 9. [38] Wadie BS, Edwan A, Nabeeh AM. Autologous fascial sling vs polypropylene tape at short-term followup: a prospective randomized study. J Urol 2005;174: [39] Ward K, Hilton P, United Kingdom and Ireland Tensionfree Vaginal Tape Trial Group. Prospective multicentre randomised trial of tension-free vaginal tape and colposuspension as primary treatment for stress incontinence. BMJ 2002;325: [40] Ward KL, Hilton P, UK and Ireland TVT Trial Group. A prospective multicenter randomized trial of tension-free vaginal tape and colposuspension for primary urodynamic stress incontinence: two-year follow-up. Am J Obstet Gynecol 2004;190: [41] Zullo MA, Plotti F, Calcagno M, et al. One-year follow-up of tension-free vaginal tape (TVT) and trans-obturator suburethral tape from inside to outside (TVT-O) for surgical treatment of female stress urinary incontinence: a prospective randomised trial. Eur Urol 2007;51: [42] Laurikainen EH, Valpas A, Kiilholma P, et al. A prospective randomized trial comparing TVT and TVT-O procedures for the treatment of SUI: immediate outcome and complications. Int Urogynecol J Pelvic Floor Dysfunct 2006;17(Suppl 2):S104 (abstract no. 77). [43] Mansoor A, Vedrine N, Darcq C. Surgery of female urinary incontinence using transobturator tape (TOT): a prospective randomized comparative study with TVT. Neurourol Urodyn 2003;22:488 9 (abstract no. 88). [44] Meschia M, Pifarotti P, Bernasconi F, et al. Multicenter randomized trial of TVT and TVT-O for the treatment of stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct 2006;17(Suppl 2):S92 3 (abstract no. 59). [45] Oliveira L, Girao M, Sartori M, Castro R, Fonesca E, Prior E. Comparison of retropubic TVT, prepubic TVT and TVT transobturator in surgical treatment of women with stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct 2006;17(Suppl 2):S253 (abstract no. 354). [46] Porena M, Kocjancic E, Costantini E, et al. Tension free vaginal tape vs transobturator tape as surgery for stress urinary incontinence: results of a multicentre randomised trial. Neurourol Urodyn 2005;24:416 8 (abstract no. 8). [47] Riva D, Sacca V, Tonta A, et al. TVT versus TOT: a randomized study at 1 year follow up. Int Urogynecol J Pelvic Floor Dysfunct 2006;17(Suppl 2):S93 (abstract no. 60). [48] Zhu L, Lang J. A prospective randomized trial comparing TVT and TOT for surgical treatment of slight and moderate stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct 2006;17(Suppl 2):S307 (abstract no. 461). [49] Bazi TM, Hamade RF, Abdallah Hajj Hussein I, Abi Nader K, Jurjus A. Polypropylene midurethral tapes do not have similar biologic and biomechanical performance in the rat. Eur Urol 2007;51:

16 678 european urology 52 (2007) [50] Latthe PM, Foon R, Toozs-Hobson P. Transobturator and retropubic tape procedures in stress urinary incontinence: a systematic review and meta-analysis of effectiveness and complications. BJOG 2007;114: [51] Oxman AD, Guyatt GH. Validation of an index of the quality of review articles. J Clin Epidemiol 1991;44: [52] Abrams P, Andersson KE, Brubaker L, et al. Recommendations for clinical research. In: Abrams P, Cardozo L, Khoury S, Wein A, editors. Incontinence, 3rd International Consultation on Incontinence. Plymouth, United Kingdom: Health Publications; p Editorial Common on: Tension-Free Midurethral Slings in the Treatment of Female Stress Urinary Incontinence: A Systematic Review and Meta-analysis of Randomized Controlled Trials of Effectiveness Elisabetta Costantini Urology Department, University of Perugia, Perugia, 06100, Italy ecostant@unipg.it In the last decade numerous trials have attempted to assess the clinical effectiveness of new devices for the treatment of stress urinary incontinence (SUI). The main issue for urologists and gynaecologists lies in making sense of a huge range of disparate literature spread over many journals and several years, generated with different brand names and generally performed in different settings. Often some trials comparing more medical devices report uncertain or even conflicting results of their net effect on continence. In a good systematic review, Novara et al provide a rational assessment, which takes great care to analyse all relevant studies and assess the quality of design and conduct in each one [1]. The authors tried to combine the findings of each study in an unbiased manner and to provide a quantitative estimate of net benefit aggregated overall, with the aim of presenting a balanced, impartial summary of existing clinical evidence. This meta-analysis has several benefits and some flaws, which deserve attention. Benefits. Many small or medium-sized trials have tried to compare the efficacy of different midurethral slings (MUSs) without pre-study power calculation or with a low power. They tend to be inconclusive and have a low external validity in answering questions about the clinical efficacy of MUSs. Statisticians advise clinicians to discount such low-power studies when making clinical decisions, claiming that low-power trials are unethical [2]. On the other hand, the so-called underpowered trials might be acceptable because they could ultimately be combined in a metaanalysis [3]. Novara et al seem to support this view and deserve praise for eliminating some selection bias by adopting a strong paper scoring methodology. Concurring with them, we consider papers with a high methodologic grade as unbiased and, even if they have a small sample, suitable for combination with similar unbiased trials in a metaanalysis. Furthermore, Novara et al reported the confidence intervals for all the studies they analysed. This worthwhile contribution could avoid the absence of evidence is not evidence of absence problem wrought by p 0.05 conclusions. Whether low-powered trials should be published irrespective of their results remains an open question. The authors concluded that...considering the overall quality of the trials included, both in terms of methodological and clinical parameters, most of the studies were of limited quality, which limits the strengths of the recommendations derived by metaanalysis... This take home message merits attention because it is drawn by the openness with which the process of achieving the final aggregate effect size has been produced by authors. This good meta-analysis will allow readers to determine for themselves just how reasonable are the decisions they make daily in clinical practice and to estimate the continence rate after MUS procedures. General flaws. Meta-analysis is defined as a statistical analysis that combines or integrates the results of several independent clinic trials considered by analyst to be combinable [4].Novaraetal realised all too well that the key difficulty lies in deciding which studies are combinable. They tried to address this issue using the Jadad score, which describes the development of an instrument to assess the quality of reports of randomised clinical trials (RCTs) [5]. This simple approach, however, introduces a selection bias that is obviated by presenting results in a funnel plot. Funnel plots display the studies in the meta-analysis as effect size plotted against sample size and help detect whether the meta-analysis has missed some trials [6]. Moreover, in reading meta-analysis results, readers must consider the so-called file drawer problem, which is the most well-known pitfall in meta-analysis about effect size. It means that negative results are omitted from the analysis