BPMT indicates behavioral therapy with pelvic floor muscle training; POPDI, Pelvic Organ Prolapse Distress Inventory; SSLF, sacrospinous ligament fixation; ULS, uterosacral ligament suspension.aScreening data not available for 17 mo from 1 site and for 2 mo from 2 sites.bMost common reasons: no stress urinary incontinence (n = 672), other medical condition (n = 228), surgery scheduled <1 month from contact (n = 55).
eTable 1. Inclusion and exclusion criteria for the OPTIMAL Trial
eTable 2. Components and Aims of OPTIMAL Perioperative Behavioral Therapy and Pelvic Floor Muscle Training Program
eTable 3. Demographics and Baseline Characteristics Across Treatment Cells
eTable 4. Surgical Procedures and Perioperative Outcomes
eTable 5. Postoperative Treatments for Urinary Incontinence or Pelvic Organ Prolapse
eTable 6. Pelvic Organ Prolapse Outcomes
eTable 7. Patient-Reported and Measured Secondary Outcomes
eTable 8. Adverse Events Related to the Surgical Outcome
eBox. Severity Grade Determined by a Modified Version of the Dindo Classification System
eTable 9. Pelvic Floor Distress Inventory Results
Barber MD, Brubaker L, Burgio KL, Richter HE, Nygaard I, Weidner AC, Menefee SA, Lukacz ES, Norton P, Schaffer J, Nguyen JN, Borello-France D, Goode PS, Jakus-Waldman S, Spino C, Warren LK, Gantz MG, Meikle SF, for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Pelvic Floor Disorders Network. Comparison of 2 Transvaginal Surgical Approaches and Perioperative Behavioral Therapy for Apical Vaginal ProlapseThe OPTIMAL Randomized Trial. JAMA. 2014;311(10):1023-1034. doi:10.1001/jama.2014.1719
More than 300 000 surgeries are performed annually in the United States for pelvic organ prolapse. Sacrospinous ligament fixation (SSLF) and uterosacral ligament suspension (ULS) are commonly performed transvaginal surgeries to correct apical prolapse. Little is known about their comparative efficacy and safety, and it is unknown whether perioperative behavioral therapy with pelvic floor muscle training (BPMT) improves outcomes of prolapse surgery.
To compare outcomes between (1) SSLF and ULS and (2) perioperative BPMT and usual care in women undergoing surgery for vaginal prolapse and stress urinary incontinence.
Design, Setting, and Participants
Multicenter, 2 × 2 factorial, randomized trial of 374 women undergoing surgery to treat both apical vaginal prolapse and stress urinary incontinence was conducted between 2008 and 2013 at 9 US medical centers. Two-year follow-up rate was 84.5%.
The surgical intervention was transvaginal surgery including midurethral sling with randomization to SSLF (n = 186) or ULS (n = 188); the behavioral intervention was randomization to receive perioperative BPMT (n = 186) or usual care (n = 188).
Main Outcomes and Measures
The primary outcome for the surgical intervention (surgical success) was defined as (1) no apical descent greater than one-third into vaginal canal or anterior or posterior vaginal wall beyond the hymen (anatomic success), (2) no bothersome vaginal bulge symptoms, and (3) no re-treatment for prolapse at 2 years. For the behavioral intervention, primary outcome at 6 months was urinary symptom scores (Urinary Distress Inventory; range 0-300, higher scores worse), and primary outcomes at 2 years were prolapse symptom scores (Pelvic Organ Prolapse Distress Inventory; range 0-300, higher scores worse) and anatomic success.
At 2 years, surgical group was not significantly associated with surgical success rates (ULS, 64.5% [100/155] vs SSLF, 63.1% [94/149]; unadjusted difference, 1.4%; 95% CI, −9.4% to 12.2%; adjusted odds ratio [OR], 1.1; 95% CI, 0.7 to 1.7) or serious adverse event rates (ULS, 16.5% [31/188] vs SSLF, 16.7% [31/186]; unadjusted difference, −0.2%; 95% CI, −7.7% to 7.4%; adjusted OR, 0.9; 95% CI, 0.5 to 1.6). Perioperative BPMT was not associated with greater improvements in urinary scores at 6 months (adjusted treatment difference, −6.7; 95% CI, −19.7 to 6.2), prolapse scores at 24 months (adjusted treatment difference, −8.0; 95% CI, −22.1 to 6.1), or anatomic success at 24 months.
Conclusions and Relevance
Two years after vaginal surgery for prolapse and stress urinary incontinence, neither ULS nor SSLF was significantly superior to the other for anatomic, functional, or adverse event outcomes. Perioperative BPMT did not improve urinary symptoms at 6 months or prolapse outcomes at 2 years.
clinicaltrials.gov Identifier: NCT00597935
Female pelvic floor disorders are a spectrum of conditions including pelvic organ prolapse and urinary incontinence. Pelvic organ prolapse occurs when the uterus descends into the lower vagina or vaginal walls protrude beyond the vaginal opening. Approximately 300 000 surgeries for prolapse are performed annually in the United States.1 Most surgery for pelvic organ prolapse (80%-90%) is performed transvaginally, with the remainder performed abdominally.1- 4 Increasingly, surgeons recognize that adequate apical (upper vaginal) support is an essential component of a durable repair.5- 7 The sacrospinous ligament fixation (SSLF) and the uterosacral ligament vaginal vault suspension (ULS) are the 2 most widely used vaginal procedures for correcting apical prolapse. The SSLF procedure suspends the vaginal apex to the sacrospinous ligament using an extraperitoneal approach whereas the ULS suspends the vaginal apex bilaterally to the proximal remnants of the uterosacral ligaments using an intraperitoneal approach. To date, no comparative data exist about the relative efficacy and safety of these 2 procedures.8
Concurrent pelvic floor disorders are common in women seeking vaginal prolapse surgery. Up to 73% report urinary incontinence, including the common subtype of stress incontinence or involuntary urine loss with coughing, sneezing, or physical activity.9 After prolapse surgery, new pelvic floor symptoms may develop while preexisting pelvic floor symptoms may improve, worsen, or remain unchanged.
As a stand-alone therapy, behavioral therapy with pelvic floor muscle training (BPMT) is an effective treatment for pelvic floor symptoms with incontinence cure rates as high as 78% and improved prolapse stage in up to 17%.10- 14 Diminished pelvic floor muscle strength has been associated with increased risk of prolapse recurrence and reoperation.15 Therefore, BPMT may be a logical adjunct if it improves surgical outcomes. Two reviews of perioperative physiotherapy for women undergoing prolapse surgery prioritized a need for robust, well-designed trials to evaluate the efficacy of perioperative BPMT.14,16
The Operations and Pelvic Muscle Training in the Management of Apical Support Loss (OPTIMAL) trial used a 2 × 2 factorial design to evaluate 2 primary aims: to compare surgical outcomes of SSLF to ULS 24 months after vaginal surgery for apical or uterine prolapse and stress incontinence and to evaluate the effect of perioperative BPMT on urinary symptoms 6 months after surgery and on anatomic outcomes and prolapse symptoms 24 months after surgery.
The design of the OPTIMAL trial has been published in detail.17 This factorial randomized trial was conducted between January 2008 and May 2013 at 9 sites participating in the Pelvic Floor Disorders Network, which is sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Eligible participants included women 18 years and older undergoing vaginal surgery for stage 2 through 4 prolapse (vaginal or uterine descent 1 cm proximal to the hymen or beyond)18 with complaints of vaginal bulge symptoms, descent of the uterus or vaginal apex at least halfway into the vagina, stress urinary incontinence symptoms, and objective demonstration of stress incontinence by office or urodynamic testing in the previous 12 months (eTable 1 in the Supplement has detailed eligibility criteria). The institutional review boards at each site approved the protocol. All participants provided written informed consent for study participation. Race/ethnicity was obtained by self-report.
Using a 2 × 2 factorial design, each enrolled patient underwent 2 distinct randomizations: first, perioperative BPMT or usual care, and second, SSLF or ULS. Participants were assigned with equal probability, using a random permuted block design generated by the data coordinating center with the randomized treatment allocations provided in 2 sequentially numbered, sealed, opaque envelopes (one for randomization to BPMT or usual care and one for randomization to ULS or SSLF). Randomization to BPMT vs usual care took place preoperatively and was stratified by clinical site. The second randomization to SSLF or ULS took place in the operating room and was stratified by surgeon and concomitant hysterectomy.
Participants underwent transvaginal surgery for pelvic organ prolapse, including the assigned apical suspension procedure. The SSLF procedure, performed unilaterally, was a modification of the Michigan 4-wall technique.19,20 The ULS procedure, performed bilaterally, was a modification of the technique described by Shull et al.21 Both apical suspension procedures used 2 permanent and 2 delayed absorbable sutures (4 sutures total).17 All patients with uterine prolapse underwent vaginal hysterectomy. A concomitant retropubic midurethral sling (tension-free vaginal tape [TVT]; Ethicon Women’s Health and Urology) was performed for stress urinary incontinence. Other concomitant surgeries were performed at the surgeon’s discretion; biologic or synthetic graft materials were not allowed for the prolapse repairs.
Usual perioperative care included routine perioperative teaching and standardized postoperative instructions. Participants randomized to perioperative BPMT received an individualized program that included 1 visit 2 to 4 weeks before surgery and 4 postoperative visits (2, 4-6, 8, and 12 weeks after surgery)17 (eTable 2 in the Supplement). Pelvic floor muscle training, individualized progressive pelvic floor muscle exercise, and education on behavioral strategies to reduce urinary and colorectal symptoms were performed at each visit. Self-reported adherence to BPMT was assessed at 6, 12, and 24 months. All BPMT interventionists attended centralized in-person training prior to the initiation of the study.
Data collection occurred at baseline, during surgery and hospitalization, and at regular intervals up to 24 months postoperatively with Pelvic Organ Prolapse Quantification (POPQ)18 evaluations and symptom assessments occurring at 6, 12, and 24 months. Interventionists for BPMT were masked to surgical randomization. All outcome assessors were masked to both perioperative BPMT and surgical intervention assignment, including research personnel who conducted vaginal examinations and trained telephone interviewers who administered patient-reported outcomes from a centralized facility. Participants were masked to the surgical group assignment, and study surgeons were masked to perioperative BPMT group assignment.
The primary outcome for surgery, assessed at 2 years, used a composite outcome measure of surgical “success” or “failure.” We defined “success” as the absence of all of the following: (1) descent of the vaginal apex more than one-third into the vaginal canal; (2) anterior or posterior vaginal wall descent beyond the hymen; (3) bothersome vaginal bulge symptoms as indicated by an affirmative response to either “Do you usually have a sensation of bulging or protrusion from the vaginal area?” or “Do you usually have a bulge or something falling out that you can see or feel in the vaginal area?” in the Pelvic Floor Distress Inventory (PFDI)22 and any response other than “not at all” to the question “How much does this bother you?”; or (4) re-treatment for prolapse by either surgery or pessary. Secondary surgical outcomes included maximum prolapse of each vaginal segment (anterior, posterior, and apical); urinary, bowel, and prolapse symptoms (PFDI, Incontinence Severity Index23); re-treatment for prolapse or urinary incontinence; and adverse events.
An independent data and safety monitoring board reviewed trial progress and safety. Investigators classified adverse events as serious/nonserious and expected/unexpected. Serious and expected adverse events were further categorized using the system by Dindo et al24 (eBox in the Supplement).
Primary outcomes for BPMT were assessed at 6 and 24 months. The primary 6-month outcome, urinary symptoms, was assessed by the Urinary Distress Inventory (UDI) score of the PFDI. The minimum important difference of the UDI is 11 points.25 The primary 24-month outcomes were prolapse symptoms, assessed by the Pelvic Organ Prolapse Distress Inventory (POPDI) score of the PFDI, and anatomic failure, defined by one of the following: descent of the vaginal apex more than one-third into the vaginal canal, anterior or posterior vaginal wall descent beyond the hymen, or re-treatment for prolapse. In contrast to the primary outcome of the surgical intervention, the presence of vaginal bulge symptoms was not included in the anatomic failure outcome for the BPMT analysis because it is assessed as a component of the POPDI. Secondary outcomes included maximum prolapse (anterior, posterior, and apical vaginal segments); re-treatment for urinary incontinence, prolapse, or both; urinary, prolapse, and bowel symptoms (PFDI)22; Incontinence Severity Index23; and pelvic floor muscle strength (Brink grading system).26
Study investigators estimated a priori that a surgical success difference of less than 15% would not change clinical practice and that the sample size should detect a difference of 10%. A sample size of 121 per surgical group would provide 80% power to detect a difference between surgical failure rates of 70% vs 85% using a 2-tailed 5% level of significance. Enrolling 170 women per surgical group would allow 80% power to differentiate between success rates of 70% and 83% using a 2-tailed 5% level of significance and also allow 80% power to identify a group difference of 0.3 SDs in mean UDI score between BPMT and usual care groups using a 2-tailed 5% level of significance. We increased our enrollment goal to 200 per group to allow for a 15% dropout rate. We stopped enrollment at 418 participants (374 randomized) because our early loss to follow-up was lower than expected. Our final sample size of 309 women with primary outcome data was sufficient to provide 80% power to detect a 15% treatment difference (noted a priori by the investigators to be clinically relevant), although the final number of participants with 24-month data was lower than expected. The study was not powered to detect interactions between the surgical and behavioral interventions.
The analysis was performed for all participants who underwent randomization for both the BPMT intervention and the surgical intervention, and participants were analyzed in the groups to which they were randomized. All statistical analyses were conducted using SAS version 9.3. Baseline demographic and clinical characteristics were compared between surgical treatment groups and between BPMT treatment assignments using general linear models for continuous outcomes and generalized linear models for categorical outcomes (GLM and LOGISTIC procedures). Baseline models included variables for surgical group, BPMT treatment assignment, and their interaction. For the primary outcome, a P value (2-sided) less than .05 was considered statistically significant. Analyses of secondary outcomes were considered exploratory in nature, and P values and confidence intervals are provided for descriptive purposes only.
Differences between the surgical groups in the primary outcome of surgical success at 24 months and other categorical outcomes were evaluated using generalized linear models (GLIMMIX procedure), with a logit link and terms for surgical group, BPMT treatment assignment, and their interaction, as well as stratification factors for surgeon and concomitant hysterectomy. Because of the large number of surgeons involved in the study (31 surgeons from 9 sites), surgeon was included in the outcome models as a random effect. If the interaction reached statistical significance at the P < .05 level, surgical groups were compared within each BPMT group; otherwise, the marginal differences between surgical groups were compared. Similar models were used to compare occurrence of adverse events except that a cumulative logit link was used for multinomial outcomes. Continuous outcomes were compared using analogous general linear models (MIXED procedure). For outcomes for which data were available at multiple time points (for example, bothersome vaginal bulge symptoms at 6, 12, and 24 months), a longitudinal extension to the generalized linear model that included terms for time as a categorical variable was used, and tests comparing the surgical groups at each time point were conducted. Longitudinal models additionally included interactions between the BPMT and surgical treatments and time.
For the primary analysis, data from the last available physical examination were used for women with missing anatomic data at the 2-year time point. Women who met failure criteria based on their last examination were considered to have surgical failures at 2 years; however, those who did not meet failure criteria and had missing data at 2 years were considered missing at 2 years for statistical analysis. In a sensitivity analysis, missing surgical failure outcomes were multiply imputed using a fully conditional specification (FCS) method that assumes the existence of a joint distribution for all variables (MI procedure). Based on the assumption that data were missing at random, independent variables in the imputation model were surgical group, BPMT treatment assignment, and their interaction; concomitant hysterectomy; and surgical failure at 6 and 12 months. A sensitivity analysis was conducted to assess the robustness of the primary analysis results. Each multiply imputed data set was analyzed separately using a model analogous to the original analysis, and results were combined using the MIANALYZE procedure to obtain inferences that accounted for both within- and between-imputation variance.
For the primary outcome of UDI score at 6 months, outcomes were imputed using Brown’s method for participants who had reported use of medication for lower urinary tract symptoms; stress incontinence surgery, including urethral bulking agent injections; neuromodulation; intravesical botulinum toxin injections; or enrollment in a supervised pelvic floor therapy program to address potential biases in the UDI introduced through those added treatments.27 The imputed UDI score at 6 months was analyzed using a Mann-Whitney-Wilcoxon test (NPAR1WAY procedure). In addition, we used a common linear mixed model (MIXED procedure) using nonimputed data that included terms for BPMT treatment, surgical treatment, and their interaction; clinical site; terms for time as a categorical variable; and the 2- and 3-way interactions of time with the treatment variables to evaluate the effect of BPMT treatment on the change from baseline in UDI at 6, 12, and 24 months and other elements of the PFDI at 6, 12, and 24 months. Two-year anatomic outcomes for the behavioral intervention were analyzed using models analogous to those described above for the surgical intervention but modified to control for site as a fixed effect rather than for hysterectomy and surgeon, reflecting the differences in the stratification factors for the BPMT and surgical randomizations. When the treatment interaction reached statistical significance at the P < .05 level, BPMT groups were compared within each surgical group; otherwise, marginal effects of the BPMT treatment groups were compared.
As with the surgical failure outcome, the anatomic failure outcome for the behavioral intervention used data from the last available physical examination for women with missing anatomic data at the 2-year time point. Women who met failure criteria based on their last examination were considered to have anatomic failures at 2 years; however, those who did not meet failure criteria and had missing data at 2 years were considered missing at 2 years for statistical analysis. In sensitivity analyses, missing anatomic failure outcomes were multiply imputed, as were changes from baseline in UDI scores at 6 months and POPDI subscale scores at 24 months for women who were missing the UDI or POPDI or who underwent stress incontinence or prolapse re-treatment, respectively. Imputation models used the FCS method and included surgical group, BPMT treatment assignment, and their interaction; clinical site; and observed outcomes at previous time points as independent variables (MI procedure). Sensitivity analyses using the multiply imputed data were conducted to assess the robustness of the original analyses. Each multiply imputed data set was analyzed separately using models analogous to the original analyses, with the exception that the models for changes from baseline in UDI and POPDI scores were not longitudinal (only the outcome at the time point of interest was modeled). Results were combined across the imputations using the MIANALYZE procedure to obtain inferences that accounted for both within- and between-imputation variance.
The OPTIMAL trial enrolled 418 eligible women and 408 women underwent the behavioral therapy randomization preoperatively. Thirty-four participants withdrew prior to surgery, leaving 374 women who were randomized to both the surgical intervention (188 for ULS, 186 for SSLF) and behavioral intervention (186 for BPMT, 188 for usual care) and were included in this analysis (Figure). The groups had similar rates of postrandomization withdrawals at 24 months (ULS, 27 [14.4%]; SSLF, 31 [16.7%]; P = .59; and BPMT, 34 [18.3%]; usual care, 24 [12.8%]; P = .15). The overall 2-year follow-up rate was 84.5%.
Baseline clinical characteristics were similar between the surgical groups with the exception of a greater degree of posterior vaginal prolapse in the SSLF group and a higher median number of vaginal deliveries in the ULS group (Table 1, Table 2, and eTable 3 in the Supplement). Baseline characteristics were similar between the behavioral intervention groups with the exception of greater anterior vaginal prolapse beyond the hymen in the usual care group. We noted significant interaction effects between surgical and BPMT groups for age and BMI; however, within BPMT groups the surgical groups were balanced. There were no BPMT or usual care group differences in surgical intervention; 50% of both groups underwent each surgical study procedure (ULS and SSLF) and all but 3 women in the study population (99%) underwent TVT (eTable 4 in the Supplement).
At 2 years, there was no statistically significant difference in surgical success as defined by the composite primary outcome (ULS, 64.5% [100/155], vs SSLF, 63.1% [94/149]; unadjusted difference, 1.4%; 95% CI, −9.4% to 12.2%; adjusted odds ratio [OR], 1.1; 95% CI, 0.7 to 1.7) between the surgical groups and no clinically significant differences in any of the 4 primary outcome components (Table 3 and Table 4). Analysis of the multiply imputed surgical failure outcome was consistent with the primary analysis (ULS, 123/188 [65.4%], vs SSLF, 121/186 [65.1%]; unadjusted difference, 0.4%; 95% CI, −9.3% to 10.0%; adjusted OR, 1.0; 95% CI, 0.6 to 1.7). Overall, 18.0% of women (55/305) developed bothersome vaginal bulge symptoms, 14.6% (45/308) had anterior or posterior prolapse or both beyond the hymen, and 5.1% (16/316) underwent re-treatment with either a pessary or surgery by 2 years. An interaction effect between surgical and BPMT groups was noted for the apical descent component of surgical success (Table 3 and Table 4). In women receiving usual care, those in the ULS group were less likely to develop apical descent than those receiving SSLF (ULS, 4.9%, vs SSLF, 15.6%; adjusted OR, 0.3; 95% CI, 0.1 to 0.8). In women receiving BPMT, there was no significant difference in apical descent (ULS, 16.2%, vs SSLF, 12.0%; adjusted OR, 1.4; 95% CI, 0.6 to 3.7).
Surgical groups were not significantly different for most secondary outcome measures, including operative variables such as estimated blood loss, time of surgery, and duration of hospitalization (eTable 4 in the Supplement) and postoperative treatments for prolapse and incontinence (eTable 5 in the Supplement). A greater proportion of women in the SSLF group had “any” or “bothersome” vaginal bulge symptoms at 6 and 12 months as compared with the women in the ULS group (eTable 6A in the Supplement). By 24 months, these proportions were similar without clinically relevant differences.
The most common perioperative adverse event was bladder perforation associated with TVT placement; the most common long-term complication was presence of vaginal granulation tissue (eTable 8 in the Supplement). The proportion of women who experienced serious adverse events during the study was not significantly different between surgical groups (ULS, 16.5%, vs SSLF, 16.7%; unadjusted difference, −0.2%; 95% CI, −7.7% to 7.4%; adjusted OR, 0.9; 95% CI, 0.5-1.6). The rate of neurologic pain requiring intervention was higher in the SSLF group (ULS, 6.9%, vs SSLF, 12.4%; adjusted OR, 0.5; 95% CI, 0.2-1.0; P = .049) and persisted to the 4- to 6-week postoperative visit in more participants (ULS, 1, [0.5%], vs SSLF, 8 [4.3%]). Ureteral obstruction was recognized and successfully managed intraoperatively in 5 (3.2%) in the ULS group. One patient’s ureteral injury was detected postoperatively after ULS (0.5%). Ureteral obstruction was not seen in the SSLF group.
There were no significant differences between BPMT and usual perioperative care in the 6-month and 24-month patient-reported primary outcomes (eTable 9 in the Supplement). After imputation by Brown’s method, the median UDI score at 6 months was 12.7 in both the BPMT and usual care groups, and a test for differences in distributions between groups was not significant (P = .61). Using nonimputed data, the adjusted mean change from baseline UDI total score at 6 months was −94.6 in the BPMT group vs −87.9 in the usual care group (95% CI for difference, −19.7 to 6.2; P = .31); these findings remained stable through 24 months. Results based on the multiply imputed change from baseline UDI at 6 months were similar (adjusted mean, −94.5 in BPMT vs −87.0 in usual care; 95% CI for difference, −19.7 to 4.9; P = .24). Compared with baseline, the decrease in POPDI score at 24 months was not significantly different between groups (adjusted mean, −73.3 in BPMT vs −65.2 in usual care; 95% CI for difference, −22.1 to 6.1; P = .26). Results from the multiply imputed POPDI scores were consistent (adjusted mean, −74.6 in BPMT vs −65.5 in usual care; 95% CI for difference, −24.6 to 6.6; P = .25). There were no significant group differences at other time points for PFDI subscales. To examine potential effect modification or confounding of outcomes by baseline pelvic floor muscle strength, these analyses were repeated including terms for baseline Brink score and Brink score × BPMT treatment assignment interaction with no substantive change in results.
There was no significant difference between the BMPT and usual care groups for the primary anatomic failure outcome at 24 months (BPMT, 37/153 [24.2%], vs usual care, 42/164 [25.6%]; adjusted OR, 0.9; 95% CI, 0.6-1.6) (Table 3). Results based on the multiply imputed anatomic failure outcome were consistent (BPMT, 45/186 [24.2%], vs usual care, 46/188 [24.5%]; adjusted OR, 1.0; 95% CI, 0.6-1.6). We did not detect group differences in the proportion of women with an anatomic failure due to anterior or posterior prolapse, or re-treatment (Table 3 and eTables 5, 6B, and 6C in the Supplement). The anterior vagina was the most likely vaginal compartment to prolapse beyond the hymen; proportions were not significantly different between groups (BPMT, 12.1%, vs usual care, 13.8%; adjusted OR, 0.9; 95% CI, 0.4-1.7) (Table 3). As described previously, there was a significant interaction between the BPMT and surgical groups such that women in the ULS group randomized to BPMT were more likely to have apical descent more than one-third of total vaginal length (Table 3 and Table 4). Apical descent in women in women randomized to SSLF was not different between behavioral groups.
No differences were noted between the BPMT and usual care groups for secondary patient-reported outcome measures, including re-treatment for incontinence (adjusted OR, 1.4; 95% CI, 0.8-2.3) or prolapse (adjusted OR, 2.5; 95% CI, 0.8-7.6) (eTables 5 and 7 in the Supplement). Baseline pelvic floor muscle strength was moderately strong, with a mean score of 8 in the Brink system (range, 3-12). No group differences in change in pelvic floor strength were noted from baseline at 6 or 24 months. At 24 months, mean Brink scores were 8.2 and 8.0 in the BPMT and usual care groups, respectively (P = .27). Self-reported performance of pelvic muscle exercises in the BPMT group was 93.4% at 6 months and 81.4% at 24 months. In the usual care group, 8 of 188 women (4.3%) received supervised BPMT outside of the study by 24 months.
In women with apical vaginal prolapse (uterine or posthysterectomy vault) and stress urinary incontinence, the OPTIMAL trial found that neither of 2 common apical transvaginal prolapse repair procedures, ULS and SSLF, was superior to the other. In addition, a multicomponent, perioperative BPMT program did not improve urinary or prolapse outcomes and is likely unnecessary as a routine aspect of perioperative care.
Our success rates for the surgical intervention, defined by a rigorous composite definition for treatment success that included anatomic results, patient reported symptoms, and re-treatment, were lower than the 70% to 90% success rates generally reported in the literature for these procedures. This is consistent with other multicenter surgical trials where treatment success rates were typically lower when defined by composite outcomes.28- 30 However, re-treatment rates remained low at 5%. Our apparently lower success rates may also be attributable to the more rigorous outcome measures we used, including masked POPQ examiners31 and strict anatomic criteria for apical descent. Estimates for anterior vaginal wall prolapse after SSLF have been as high as 40%,32,33 as reported in case series analyses. These estimates were made without the benefit of high-quality clinical trial evidence. The high rates of anterior vaginal prolapse seen in these series have been attributed to posterior deviation of the vaginal apex, which may predispose to anterior wall descent. Our findings showed that the proportion of women with recurrent anterior (ULS, 12.9%, vs SSLF, 13.1%) or posterior prolapse (ULS, 1.9%, vs SSLF, 3.3%) beyond the hymen were not significantly different between treatment groups, highlighting the importance of establishing surgical outcomes information on prospective, rigorously controlled clinical trials rather than on observational data.
One unexpected finding was that, compared with usual care, women receiving BPMT and randomized to receive ULS had greater apical descent; this was not seen in those randomized to receive SSLF. It is unclear why more apical descent was observed in women treated with BPMT, but one possible explanation may be the difference in orientation of the vagina between the 2 suspension procedures, because SSLF results in a posterior-lateral deviation of the vagina while ULS maintains normal vaginal orientation.
The low rates of serious adverse events seen in both groups are consistent with prior clinical experience regarding the safety of native tissue vaginal reconstructive surgery.34 Fewer than 1 in 5 women experienced a serious adverse event over the 2-year follow-up, with less than 5% directly related to the index surgery. Because of the differing anatomical approach between the 2 operations, we observed more ureteral obstructions after ULS (3.2%) than SSLF (0%). These rates were consistent with previously reported ureteral injury rates, which range from 1% to 11% after ULS.35 Notably, all ureteral obstructions identified at the time of surgery were adequately treated during the index surgery by removing the obstructing sutures or by placing a ureteral stent. Our results confirm the findings from previous case series suggesting that SSLF may cause acute neurologic pain, particularly buttock pain that may be the result of gluteal nerve entrapment.32,36 The majority of patients had resolution of the pain by 4 to 6 weeks after surgery. Persistent pain occurred in 4.3% after SSLF, highlighting the need to provide preoperative counseling to patients about this potential risk.
Frawley et al37 found no significant effect of perioperative physiotherapist-supervised pelvic floor muscle training for women undergoing vaginal surgery for prolapse or hysterectomy, observations consistent with our results. Although their intervention included more sessions (8) over a longer period of time (12 months), their study also did not detect significant group differences 12 months after surgery on urinary questionnaires, bladder diary, or pad test.
Jarvis and colleagues38 did report improved outcomes from perioperative physiotherapy 3 months after prolapse, stress incontinence surgery, or both. They found significant group differences in urinary symptoms, quality of life, pelvic floor muscle strength, and voiding frequency. Despite the similarities to our OPTIMAL trial, there are important differences, including a smaller number of patients (n = 60) and different outcome measures assessed at an earlier time point (3 months).38 Both the Frawley et al and Jarvis et al studies used established interventional physiotherapists to deliver BPMT, whereas we provided centralized training for clinicians with varying degrees of BPMT experience. In OPTIMAL, BPMT was only administered by clinicians certified after rigorous in-person testing.17 Because the clinicians administering BPMT in OPTIMAL had varying experience, our study is more generalizable to clinical practice than prior trials of BPMT.
The outcomes in this study should not be extrapolated to women who do not match our eligibility criteria, including women who do not undergo concomitant midurethral sling for treatment of stress incontinence. Our participants underwent both prolapse and stress incontinence procedures that had high efficacy rates, which may have obviated any potential improvement from perioperative BPMT intervention. Our findings should also not be extrapolated to women undergoing transvaginal mesh or abdominal mesh augmented prolapse repairs.
The OPTIMAL study’s strengths include a robust study design, standardized anatomic and functional outcomes with validated patient-reported outcomes, and patients and outcome assessors blinded to the surgical intervention assignment. Our study also benefited from the multicenter, multisurgeon, randomized design, with standardization of surgical techniques and the high rate of participant retention. In addition, perioperative BPMT program intervention was individualized using a standard protocol and consisted of multiple components, including strategies for stress and urgency incontinence, recommendations for normal voiding and defecation techniques, and ongoing reinforcement of functional bracing (pelvic floor contraction during lifting and physical activity) thought to protect the surgical repair and the pelvic floor long-term.
This study provides evidence for patients and their surgeons about the benefits, risks, and complications of 2 widely used native tissue vaginal approaches for apical prolapse, as well as the role of perioperative BPMT. Although our results do not support routinely offering perioperative BPMT to women undergoing vaginal surgery for prolapse and stress urinary incontinence, previous evidence supports offering individualized treatment, including behavioral or physical therapy, to those who report new or unresolved pelvic floor symptoms.10- 14 Our surgical outcomes inform preoperative discussions that include a patient’s preferences for anatomic and subjective outcomes as well as consideration of likely and possible adverse events. Although variability in surgical recommendations for vaginal prolapse repair is likely to persist because of individual patient characteristics, our data provide a metric against which other vaginal procedures, including those that use synthetic or biologic mesh, can be assessed.
In women undergoing vaginal surgery for pelvic organ prolapse and stress urinary incontinence, results for anatomic, functional, and adverse events 2 years after surgery for ULS or SSLF were similar. Perioperative BPMT for these women did not improve urinary symptoms at 6 months or prolapse outcomes 2 years after surgery.
Corresponding Author: Matthew D. Barber, MD, MHS, Obstetrics/Gynecology and Women’s Health Institute, Cleveland Clinic, 9500 Euclid Ave, Desk A81, Cleveland, OH 44195 (firstname.lastname@example.org).
Author Contributions: Dr Barber had full access to all of 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: Brubaker, Burgio, Richter, Nygaard, Barber, Menefee, Norton, Schaffer, Borello-France, Goode, Spino, Barber.
Acquisition of data: Brubaker, Richter, Nygaard, Menefee, Lukacz, Norton, Schaffer, Nguyen, Jakus-Waldman, Warren, Meikle, Barber.
Analysis and interpretation of data: Brubaker, Burgio, Nygaard, Menefee, Lukacz, Norton, Schaffer, Nguyen, Borello-France, Goode, Jakus-Waldman, Spino, Warren, Gantz, Meikle, Barber.
Drafting of the manuscript: Brubaker, Burgio, Richter, Nygaard, Barber, Menefee, Lukacz, Schaffer, Nguyen, Borello-France, Jakus-Waldman, Spino, Warren, Gantz, Meikle, Barber.
Critical revision of the manuscript for important intellectual content: Brubaker, Burgio, Richter, Nygaard, Menefee, Lukacz, Norton, Schaffer, Nguyen, Borello-France, Goode, Jakus-Waldman, Spino, Warren, Gantz, Meikle, Barber.
Statistical analysis: Spino, Warren, Gantz, Meikle, Barber.
Obtained funding: Brubaker, Burgio, Nygaard, Norton, Schaffer, Spino, Meikle, Barber.
Administrative, technical, and material support: Brubaker, Barber, Norton, Schaffer, Spino, Meikle, Barber.
Study supervision: Burgio, Richter, Menefee, Schaffer, Goode, Spino, Gantz, Meikle, Barber.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Barber reported having received a research grant from the Foundation for Female Health Awareness and royalties from UptoDate and Elsevier. Dr Brubaker reported having received royalties from UptoDate. Dr Burgio reported having received a research grant from Pfizer and being a consultant for Pfizer and Astellas. Dr Richter reported having received research grants from Astellas, the University of California/Pfizer, and Pfizer; being a consultant for the Astellas Advisory Board, GlaxoSmithKline, Uromedica, IDEO, and Xanodyne; and receiving an education grant from Warner Chilcott. Dr Lukacz reported having received a research grant from Renew Medical and an educational grant from Ethicon/Johnson & Johnson; being a consultant for Pfizer, Renew Medical, and American Medical Systems; and receiving payment for the development of educational content for Sharp Chula Vista. Dr Schaffer reported having received research support from Boston Scientific, being a consultant for Ferring Pharmaceuticals, serving on an advisory board and a speakers bureau for Astellas and Cadence Pharmaceuticals, and receiving royalties from McGraw-Hill. Dr Goode reported having received a research grant from Pfizer and serving as a consultant for Astellas. No other disclosures were reported.
Funding/Support: This research was supported by grants U01 HD041249, U10 HD041250, U10 HD041261, U10 HD041267, U10 HD054136, U10 HD054214, U10 HD054215, U01 HD069031, and U10 HD054241 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women’s Health.
Role of the Sponsor: The Eunice Kennedy Shriver National Institute of Child Health and Human Development project scientist for the Pelvic Floor Disorders Network, Anne Weber, MD, had a role in the study design. Dr Meikle became the project scientist just as the study was initiated and had a role in conduct of the study; the collection, analysis, and interpretation of the data; and in the preparation, review, and approval of the manuscript.
Pelvic Floor Disorders Network (PFDN) Members: In addition to the authors, the following members of the Pelvic Floor Disorders Network participated in the Operations and Pelvic Muscle Training in the Management of Apical Support Loss (OPTIMAL) trial: RTI International, Research Triangle Park, North Carolina (PFDN Data Coordinating Center, July 1, 2011, to present): Dennis Wallace, Kevin A. Wilson, Daryl Matthews, Tamara L. Terry, Jutta Thornberry, Amanda Youmans-Weisbuch, Ryan E. Whitworth, Michael P. Hieronymus. University of Michigan, Ann Arbor (PFDN Data Coordinating Center, until July 1, 2011): Morton Brown, Nancy Janz, John Wei, Xiao Xu, Beverley Marchant, Donna DiFranco, Yang Casher, Kristina Slusser, Zhen Chen. Cleveland Clinic, Cleveland, Ohio: Mark D. Walters, J. Eric Jelovsek, Marie F. R. Paraiso, Beri M. Ridgeway, Ly Pung, Cheryl Williams, Linda McElrath, Betsy O’Dougherty, Megan Edgehouse, Gouri Diwadkar, Anna Frick. Loyola University Chicago, Illinois: Mary Tulke, Elizabeth Mueller, Kimberly Kenton, Kathleen Jesse. University of California, San Diego, Health Systems: Charles W. Nager, Michael E. Albo, Cara Grimes, Heidi W. Brown, Anna C. Kirby, Leah Merrin, JoAnn Columbo, Nehal Mehta. Southern California Kaiser Permanente, Downey: Mercedes Cardona, Eudocia Zapata. Southern California Kaiser Permanente, San Diego: Emily L. Whitcomb, Keisha Y. Dyer, Karl M. Luber, Jasmine Tan-Kim, Gouri B. Diwadkar, Lynn M. Hall, Linda M. Mackinnon, Gisselle Zazueta-Damian. University of Utah, Salt Lake City: Yvonne Hsu, Jan Baker, Linda Freedman, Linda Griffin, Maria Masters, Amy Orr, Kristina Heintz. University of Alabama at Birmingham: R. Edward Varner, Robert Holley, William J. Greer, L. Keith Lloyd, Tracy S. Wilson, Alayne Markland, Jonathan L. Gleason, Alicia Ballard, Candace Parker-Autry, Lisa Pair, Velria Willis, Nancy Saxon, Lachele Ward, Kathy Carter, Julie Burge. Duke University Medical Center, Durham, North Carolina: Anthony G. Visco, Cindy L. Amundsen, Nazema Y. Siddiqui, Jennifer M. Wu, Mary Raynor, Mary McGuire, Ingrid Harm-Ernandes. University of Texas Southwestern Medical Center, Dallas: David Rahn, Marlene Corton, Clifford Wai, Kelly Moore, Shanna Atnip, Pam Martinez, Deborah Lawson. Formerly Eunice Kennedy Shriver National Institute of Child Health and Human Development: Anne Weber. PFDN Steering Committee Chair: Katherine Hartmann.
Correction: This article and its supplemental content were corrected online June 25, 2015, for errors in the outcome data.