Background
Given that the number of surgeries for pelvic organ prolapse is expected to increase worldwide, knowledge on risk factors for prolapse recurrence is of importance for developing preventive strategies and shared decision-making.
Objective
To identify risk factors for subjective and objective failure after either sacrospinous hysteropexy or vaginal hysterectomy with uterosacral ligament suspension over a period of 5 years after surgery.
Study Design
This was a secondary analysis of the 5-year follow-up of the SAVE-U trial. The SAVE-U trial was conducted in 4 Dutch hospitals. A total of 208 women with uterine prolapse stage ≥2 were randomized to sacrospinous hysteropexy or vaginal hysterectomy with uterosacral ligament suspension. For the current analysis, available annual 5-year follow-up data of 207 women were analyzed. Without missing values this analysis would have included 1035 measurements in total over the 5-year follow-up. Recurrences were analyzed as “events” using generalized linear mixed models because recurrences of anatomic failure and bothersome vaginal bulge symptoms fluctuated over time. The primary outcome was the composite outcome of failure defined as prolapse beyond the hymen, bothersome bulge symptoms, repeated surgery, or pessary use for recurrent prolapse. Secondary outcome measures were bothersome vaginal bulge symptoms, overall anatomic failure (Pelvic Organ Prolapse Quantification stage ≥2 in any compartment), apical compartment recurrence (Pelvic Organ Prolapse Quantification stage ≥2), anterior compartment recurrence (Pelvic Organ Prolapse Quantification stage ≥2), and posterior compartment recurrence (Pelvic Organ Prolapse Quantification stage ≥2).
Results
For the composite outcome of failure (164 events in 66 different women), statistically significant risk factors were: body mass index (odds ratio, 1.10 [per 1 kg/m 2 ]; 95% confidence interval, 1.02–1.19; P =.02), smoking (odds ratio, 2.88; 95% confidence interval, 1.12–7.40; P =.03), and preoperative Pelvic Organ Prolapse Quantification point Ba (odds ratio, 1.23 [per 1 cm]; 95% confidence interval, 1.01–1.50; P =.04). When analyzing each surgical outcome measure separately, body mass index and Pelvic Organ Prolapse Quantification point Ba were risk factors for overall anatomic failure (462 events in 147 women; odds ratio, 1.15; 95% confidence interval, 1.07–1.25; P <.01 and odds ratio, 1.14; 95% confidence interval, 1.00–1.30; P =.05, respectively) and anterior compartment recurrence (385 events in 128 women; odds ratio, 1.11; 95% confidence interval, 1.02–1.22; P =.02 and odds ratio, 1.17; 95% confidence interval, 1.02–1.34; P =.02, respectively). Vaginal hysterectomy was a risk factor for posterior compartment recurrence when compared with sacrospinous hysteropexy (93 events in 40 women; odds ratio, 5.21; 95% confidence interval, 2.05–13.27; P <.01). Smoking was a risk factor for bothersome vaginal bulge symptoms (70 events in 41 women; odds ratio, 3.80; 95% confidence interval, 1.48–9.75; P =.01), and preoperative Pelvic Organ Prolapse Quantification stage 3 or 4 was significantly protective against bothersome bulge symptoms (odds ratio, 0.32; 95% confidence interval, 0.11–0.89; P =.03).
Conclusion
Body mass index, smoking, and Pelvic Organ Prolapse Quantification point Ba were statistically significant risk factors for the composite outcome of failure (prolapse beyond the hymen, bothersome bulge symptoms, repeated surgery, or pessary use for recurrent prolapse) in the period of 5 years after surgery.
Introduction
Pelvic organ prolapse (POP) is a prevalent condition that can greatly reduce a woman’s quality of life. Worldwide, a large number of operations for POP are performed every year, which is expected to increase in the coming 20 to 40 years. In the Netherlands, nearly 9000 operations for uterine prolapse are performed annually. Most consist of native tissue vaginal repair in combination with vaginal hysterectomy (VH) with uterosacral ligament suspension, modified Manchester procedures, or sacrospinous hysteropexy (SSH). Because of the scarcity in solid evidence comparing these operations, strict guidelines are lacking, and the choice of operation is mainly based on surgeon experience and patient preference. To improve shared decision-making, patient risk factors should also be considered in a personalized decision process. Knowledge of risk factors not only benefits tailored management of POP, but is also essential in prevention of POP and its recurrence. In the past decade, several studies have investigated risk factors for POP recurrence. A recent meta-analysis identified preoperative POP Quantification (POP-Q) stage and younger age as risk factors for POP recurrence (Schulten et al. 2021, unpublished data), whereas other studies identified family history as a risk factor. , Most of these studies focused on objective recurrence, combined data of mesh and nonmesh surgeries, and lacked long-term follow-up.
Why was this study conducted?
Knowledge on risk factors for prolapse recurrence is of importance for developing preventive strategies.
Key findings
Risk factors for the composite outcome of failure within 5 years after surgery are body mass index (BMI), smoking, and Pelvic Organ Prolapse Quantification (POP-Q) point Ba. Risk factors for overall anatomic failure and anterior compartment recurrence within 5 years are BMI and POP-Q point Ba. Vaginal hysterectomy is a risk factor for posterior compartment recurrence. Smoking is a risk factor for bothersome bulge symptoms, whereas preoperative POP-Q stage 3 or 4 is protective against bothersome bulge symptoms.
What does this add to what is known?
This secondary analysis of the SAVE-U trial presents recurrence risk factors within 5 years after prolapse surgery for multiple outcome measures.
The SAVE-U trial was a large randomized controlled trial (RCT) comparing the effectiveness of SSH with that of VH with uterosacral ligament suspension over a follow-up period of 5 years. At 5-year follow-up, significantly fewer anatomic recurrences of the apical compartment with bothersome bulge symptoms or repeat surgery were found after SSH than after VH with uterosacral ligament suspension. Furthermore, after SSH, more women had the composite outcome of success. The purpose of the current study is to perform a secondary analysis of the SAVE-U data to identify the risk factors associated with subjective and objective outcome measures over a period of 5 years after surgery. The hypothesis is that younger age, preoperative POP-Q stage, and VH are risk factors for POP recurrence.
Materials and Methods
We conducted a secondary analysis of the results over a 5-year follow-up period of the SAVE-U trial. This was a nonblinded, multicenter, noninferiority RCT conducted between 2009 and 2012 in 4 nonuniversity teaching hospitals in the Netherlands. For this analysis, the data of the 2 randomization groups were combined into 1 group and treated as a prospective cohort.
The details of the original trial protocol were published in 2011. Briefly, the trial was designed to compare uterus-sparing SSH with VH with uterosacral ligament suspension in women with uterine prolapse stage ≥2. Women were excluded in case of previous pelvic floor surgery, known malignancy, an abnormal cervical smear result, a wish to preserve fertility, language barriers, immunologic or hematologic diseases interfering with postoperative recovery, abnormal ultrasound findings of the uterus or ovaries, or abnormal uterine bleeding. The women were randomized in a 1:1 ratio stratified by hospital and stage of uterine prolapse. SSH was performed using 2 permanent sutures (Prolene 1.0; Ethicon, Raritan, NJ), which were placed in the sacrospinous ligament at least 2 cm from the ischial spine. Uterosacral ligament suspension involved the attachment of the uterosacral ligaments to the vaginal vault with 2 delayed absorbable sutures (Vicryl 1.0, Ethicon). Concomitant anterior or posterior colporrhaphy and antiincontinence surgery was allowed if indicated. All women gave written informed consent before randomization, and the institutional review boards of all participating hospitals approved the study (MEC 09-0625, August 18, 2009).
The primary objective of the original SAVE-U trial was to compare surgical failure of the apical compartment 12 months after SSH vs after VH. Surgical failure of the apical compartment was defined as a recurrent prolapse stage ≥2 (POP-Q point C ≥ -1 cm) of the apical compartment (uterus or vaginal vault) in combination with bothersome bulge symptoms or repeated surgery for apical prolapse. Follow-up included annual outpatient visits until 5 years after surgery, with evaluation of POP using the POP-Q system and completion of validated questionnaires before every visit.
For this secondary analysis, annual 5-year follow-up data of all women who underwent SSH or VH were used to identify risk factors. All women were analyzed “as treated” according to the original study. The primary outcome was “composite outcome of failure” defined as a prolapse beyond the hymen in any compartment or bothersome bulge symptoms or repeated surgery or pessary use for recurrent prolapse in the 5 years after surgery. Bothersome bulge symptoms were defined as a positive answer to any of the following questions from the urogenital distress inventory: “Do you experience a sensation of bulging or protrusion from the vagina?” and “Do you have a bulge or something falling out that you can see in the vagina?” in combination with the responses “somewhat bothered” to “very much bothered.” The analysis was also performed for the separate outcome measures including bothersome vaginal bulge symptoms, overall anatomic failure (POP-Q stage ≥2 in any compartment), apical compartment recurrence (POP-Q stage ≥2), anterior compartment recurrence (POP-Q stage ≥2), and posterior compartment recurrence (POP-Q stage ≥2). In addition, a sensitivity analysis was performed for the outcome measures of overall anatomic failure beyond the hymen and anterior compartment recurrence beyond the hymen.
We performed a generalized linear mixed-model analysis for the annual follow-up data until 5 years after surgery, with a binomial distribution and logit link, and an autoregressive correlation structure of order 1 (AR[1]) for the repeated measures. This approach was chosen instead of a survival analysis because the outcomes varied over time. Smoking had 29 (14%) missing values. Smoking status was determined by a positive answer on the baseline questionnaire to the question “Do you smoke?” in combination with the number of cigarettes per day. Women who smoked on a daily basis were considered smokers. Body mass index (BMI) had 9 (4%) missing values. There were no baseline POP-Q measurements available for 5 (2%) women, leading to missing values for preoperative POP-Q stage and POP-Q points Ba, C, and HG. There were no missing values for age, vaginal parity, and type of surgery. Multiple imputation using fully conditional specification (chained equations) was applied to impute the missing values for smoking, and 10 data sets were created. Because the generalized linear mixed-model procedure of IBM SPSS Statistics (version 25.0.0.1; IBM, Armonk, NY) is not able to work with multiply imputed data, we calculated the average of the imputed smoking values per person with missing data. All available baseline characteristics, operative variables, and outcome data were used for imputation.
A preselection of possible risk factors was made on the basis of current literature, , and the number of risk factors for analysis was limited to approximately 10% of the number of failures. The selected risk factors were age (<60 vs ≥60 years), BMI (per 1 kg/m 2 ), smoking status (yes or no), vaginal parity (per 1), type of surgery as treated (SSH or VH), preoperative POP-Q stage (stage 2 vs stage 3 or 4), number of operated compartments (1 or 2 vs 3 compartments, depending on performed anterior and/or posterior colporrhaphy), and preoperative POP-Q points Ba, Bp, C, and GH. All selected risk factors were included into the multivariable analyses for the following outcomes: composite outcome of failure, overall anatomic failure, and anterior compartment recurrence. To avoid overfit of the models, for posterior compartment recurrence, all variables except POP-Q points Ba and C were taken into the analysis. Only age, BMI, smoking, vaginal parity, preoperative POP-Q stage, and POP-Q points Ba and HG were included into the analysis for the bothersome vaginal bulge symptoms outcome, and only BMI, POP-Q point C, and type of surgery for apical compartment recurrence. Regarding the sensitivity analysis, age, BMI, smoking status, preoperative POP-Q stage, and POP-Q points Ba and Bp were included into the analysis for overall anatomic failure beyond the hymen. The same variables, except POP-Q point Bp, were included into the analysis for anterior compartment recurrence beyond the hymen. Results of the multivariable analyses are presented as odds ratios (ORs) with corresponding 95% confidence intervals (CIs). For the composite outcome of failure, model-based probabilities of failure were calculated for the different levels of the statistically significant risk factors using the ORs of the full model, under the assumption that the study cohort was representative of the population of patients needing such surgery. First the probability of a composite outcome of failure during 5 years after surgery was calculated for a “reference person,” after which probabilities were calculated for different levels of BMI, smoking, and POP-Q point Ba, respectively. The reference values were based on the mean baseline characteristics. Because the type of surgery was not a statistically significant risk factor for the composite outcome of failure, the probabilities were not calculated for both surgery types separately, but the mean “surgery” value was used. All analyses were performed with IBM SPSS Statistics for Windows (version 25.0.0.1; IBM corp, Armonk, NY).
Results
A total of 208 women were enrolled in the SAVE-U trial and randomly assigned to SSH or VH with uterosacral ligament suspension. For this study, 5-year annual follow-up data of 207 women were analyzed. One woman was excluded because she underwent abdominal hysterectomy. The flow diagram and description of dropouts during the follow-up were published previously. Patient characteristics of all 207 women are shown in Table 1 .
| Characteristics | Total n=207 |
|---|---|
| Median (range) age (y) | 62.2 (33–85) |
| Mean (SD) BMI (kg/m 2 ) | 25.9 (3.4) |
| Postmenopausal | 171 (83) |
| Highest educational level: | |
| Primary or secondary school | 21 (10) |
| High school | 160 (77) |
| Bachelor, master, or university degree | 22 (11) |
| Comorbidity: | |
| Cardiovascular disease | 71 (34) |
| Diabetes mellitus | 10 (5) |
| Respiratory disease | 10 (5) |
| Smoker | 22 (11) |
| Median (range) number of vaginal deliveries | 3 (0–7) |
| Cesarean deliveries | 9 (4) |
| Forceps deliveries | 16 (8) |
| Vacuum deliveries | 13 (6) |
| Median (range) POP-Q a C (cm) | 0 (−1 to 10) |
| Median (range) POP-Q a Ba (cm) | 2 (−3 to 8) |
| Median (range) POP-Q a Bp (cm) | −2 (−3 to 8) |
| Prolapse beyond hymen | |
| Apical (POP-Q a C > 0) | 91 (44) |
| Anterior (POP-Q a Ba > 0) | 142 (69) |
| Posterior (POP-Q a Bp > 0) | 22 (11) |
| Overall POP-Q stage a | |
| 2 | 61 (29) |
| 3 | 131 (63) |
| 4 | 10 (5) |
| Type of surgery | |
| Sacrospinous hysteropexy | 107 (52) |
| Vaginal hysterectomy b | 100 (48) |
| Anterior colporrhaphy | 203 (98) |
| Posterior colporrhaphy | 82 (40) |
| Anterior and posterior colporrhaphy | 82 (40) |
a System involves quantitative measurements of various points of vaginal wall with hymen as reference point. Degree of prolapse of anterior vaginal wall (Ba), posterior vaginal wall (Bp), and uterus or vaginal vault (C) measured in centimeters both above or proximal to hymen (negative number) or beyond or distal to hymen (positive number), with plane of hymen defined as 0. B is the most descended edge on the anterior (Ba) and posterior (Bp) vaginal wall. POP-Q stage 2: most distal prolapse is between 1 cm above and 1 cm beyond hymen; stage 3: most distal prolapse is prolapsed >1 cm beyond hymen but no further than 2 cm less than total vaginal length; stage 4: total prolapse
b Vaginal hysterectomy was performed with the McCall procedure in 6 cases.
Table 2 shows the results of the multivariable analyses for the 6 different outcome measures. As a result of a small number of events, we were not able to identify risk factors for surgical failure of the apical compartment (27 events in 13 women) and retreatment (ie, repeated surgery [20 events in 10 different women] or pessary [15 events in 7 women]). Table 2 also presents the events per outcome per year and the total events over 5 years. There seemed to be a peak in the number of events at year 2 and 3 for developing anatomic recurrence, mainly visible for the overall anatomic failure and anterior compartment recurrence outcomes.
| Follow-up and variables | Composite outcome of failure | Bothersome vaginal bulge | Overall anatomic failure | Apical recurrence | Anterior recurrence | Posterior recurrence | |
|---|---|---|---|---|---|---|---|
| Follow-up | Number of events/women | Number of events/women | Number of events/women | Number of events/women | Number of events/women | Number of events/women | |
| Year 1 | 30/198 | 9/196 | 92/197 | 8/196 | 77/195 | 17/195 | |
| Year 2 | 36/187 | 18/196 | 104/185 | 7/185 | 91/185 | 18/185 | |
| Year 3 | 32/182 | 10/193 | 102/181 | 4/181 | 83/183 | 23/183 | |
| Year 4 | 39/178 | 20/190 | 87/177 | 7/177 | 74/178 | 17/178 | |
| Year 5 | 27/168 | 13/184 | 77/168 | 5/169 | 61/168 | 18/168 | |
| Total number of events/ measurement | 164/913 | 70/959 | 462/908 | 31/908 | 386/909 | 93/909 | |
| Number of different women with event | 66/207 | 41/207 | 147/207 | 13/207 | 128/207 | 40/207 |
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