Medium-term outcomes 2 years after laparoscopic sacrocolpopexy: a retrospective cohort study in Japan

Abstract This study was performed to investigate medium-term outcomes and reoperation rates after laparoscopic sacrocolpopexy (LSC). We examined 119 patients undergoing LSC for symptomatic pelvic organ prolapse (POP). The primary outcomes were subjective failure and anatomical failure at 2 years; a score ≥ 2 on question 3 of the PFDI-20 was considered to indicate subjective failure. POP-Q stage 2 or higher in any compartment was considered to indicate anatomical failure. Secondary outcomes were reoperations for POP recurrence, mesh-related complications, and stress urinary incontinence (SUI). The rates of subjective failure and anatomical failure were 4.2% (n = 5) and 9.2% (n = 11), respectively. Reoperations were needed in 13.4% (n = 16) of patients, including SUI with tape procedure in 7.5% (n = 9), POP recurrence in 4.2% (n = 5), and mesh-related complications in 1.6% (n = 2). The subjective failure rate at 2 years after LSC was acceptably low. Impact Statement What is already known on this subject? Laparoscopic sacrocolpopexy (LSC) has clinical efficacy equivalent to open sacrocolpopexy, and there is evidence that LSC involves less blood loss and shorter length of hospital stay. However, there is still insufficient evidence to assess medium-term outcomes after LSC in Japan. What the results of this study revealed? The findings of this study showed excellent medium-term rates of subjective failure (4.2%) and anatomical failure (8.4%) after LSC. We demonstrated that patients with persistent postoperative vaginal bulge (subjective failure) also had no improvement in postoperative urinary and colorectal symptoms. Our cohort had low rates of reoperation (13.4%) after LSC. The most common reoperations were for stress urinary incontinence (SUI) (7.5%), followed by pelvic organ prolapse (POP) recurrence (4.2%) and mesh-related complications (1.6%). What are the implications of these findings in clinical practice and/or further research? This study showed that LSC is a safe and effective treatment for POP. Comparative evaluation of anatomical outcomes and the patient’s condition is required to understand the extent to which LSC positively impacts a woman’s pelvic floor-related quality of life.


Introduction
The lifetime risk of undergoing surgery to address either stress urinary incontinence (SUI) or pelvic organ prolapse (POP) is 20.5% (Wilkins and Wu 2017). In addition to a sensation of bulging tissue, POP is commonly associated with symptoms/sequelae of urinary and defecatory dysfunction (Jelovsek et al. 2007).
Laparoscopic sacrocolpopexy (LSC) has similar outcomes to open sacrocolpopexy, and there is evidence that LSC involves less blood loss and shorter length of stay (Coolen et al. 2013;Freeman et al. 2013).
POP can have a meaningful influence on a woman's quality of life (QOL) (Barber et al. 2005), greatly affecting daily activities and causing a negative body image for women. Therefore, it is meaningful to measure QOL of women with POP when evaluating the effectiveness of a surgical intervention or comparing the seriousness of symptoms among patients or groups (Barber et al. 2005). Barber et al. (2009) reported that the absence of vaginal bulge symptoms postoperatively is significantly related with patient evaluations of overall satisfaction with the surgery. Moreover, there is not always a correlation between severity of POP and symptoms (Ellerkmann et al. 2001;Fitzgerald et al. 2007), and anatomical findings may not correspond to a patient's perception (e.g. for postoperative urinary, sexual, and defecatory symptoms) (Gelhorn et al. 2012). Therefore, comparative evaluation of anatomical outcomes and the patient's condition is necessary to sufficiently understand the extent to which prolapse surgery impacts a woman's QOL.
In addition, there has been a lack of research regarding medium-term outcomes after LSC in Japanese women with regard to reoperations, mesh-related complications, POP recurrence, de novo or persistent SUI after LSC. Therefore, we report the medium-term subjective failure rates based on patient-reported outcomes (PROs) and anatomical failure rates.

Study design
This was a retrospective cohort study of consecutive patients who underwent LSC for POP between August 2015 and February 2019 at the Department of Urology, Hokusuikai-Kinen Hospital.

Data collection
After the study protocol was approved by the institutional review board (approval number: 2021-059), we used medical charts to compile demographic data: age, body mass index, parity, comorbidities, gynecological history and related pelvic, urinary, and colorectal symptoms in February 2021. The Pelvic Floor Distress Inventory-20 (PFDI-20) (Yoshida et al. 2013) was used to measure the severity of relevant symptoms, and the International Consultation of Incontinence Questionnaire Short Form (ICIQ-SF) (Gotoh et al. 2009) was used to measure symptoms of SUI. Subscales of the PFDI included the Pelvic Organ Prolapse Distress Inventory-6 (POPDI-6), the Urinary Distress Inventory-6 (UDI-6), and the Colorectal-Anal Distress Inventory-8 (CRADI-8). These subscales were measured before LSC and at the 2-year followup visit.
We also collected information on rates of POP recurrence, mesh-related complications, and de novo or persistent SUI indicating the need for reoperation along with the timing of their occurrence.
The exclusion criteria were LSC performed using only an anterior mesh graft, patients who were lost to follow-up, and those who did not complete the questionnaires. We performed LSC with double mesh according to the basic technique proposed by Wattiez et al. (2001). The inclusion criteria for this study were LSC with concomitant supracervical hysterectomy or uterine preservation for preoperative Pelvic Organ Prolapse Quantification (POP-Q) stage 2 or greater (Bump et al. 1996) and patients who completed the preoperative and postoperative questionnaires and underwent routine physical examination to evaluate postoperative complications and anatomical failure. The general stage of POP was defined as the most severe stage in one or more of the anterior, apical, and posterior vaginal compartments. Supracervical hysterectomy or uterine preservation was selected based on the results of preoperative consultation with the patient and the patient's wishes after appropriate counselling. Patients with subjective failure at 2 years postoperatively were compared to those without failure. The primary outcomes were subjective failure, which was defined as the proportion of patients with a score of 2, 3, or 4 points on question 3 of PFDI-20, and anatomical failure affecting any compartments (Pelvic Organ Prolapse Quantification [POP-Q] stage 2 or greater) at 2 years. The secondary outcomes were reoperation for POP recurrence, mesh-related complications, or de novo or persistent SUI. SUI was evaluated by the ICIQ-SF questionnaire (question 6: "When does urine leak?"), and a diagnosis of SUI was made in patients reporting urine leakage on coughing, sneezing, or physical activity. Moreover, SUI was assessed during physical examination on prolapse reduction with a cough stress test for occult SUI. We defined de novo SUI as the development of new-onset SUI after LSC in women with no obvious or occult SUI before LSC.
The patients were followed up at the clinic at 1, 3, and 6 months after LSC and then yearly as above using questionnaires and physical examination. If a patient did not complete the questionnaires in the clinic, they were requested to return the completed questionnaires and all available forms were collected by mail by February 2021.

Surgical technique
Surgeries were performed at Hokusuikai-Kinen Hospital by a trained urologist. Briefly, two pieces of polypropylene mesh (GYNEMESH PS; Ethicon, Somerville, NJ) were used for LSC. In patients with a uterus, supracervical hysterectomy was typically performed. When uterus preservation was required, the anterior mesh strip was Y-shaped and penetrated through the broad ligament. Then, posterior dissection of the levator ani muscles was performed bilaterally, and posterior mesh was fixed to the levator ani muscles using non-absorbable sutures (Tefdesser II; Kono Seisakusyo, Chiba, Japan). Anterior dissection of the bladder neck was performed. The anterior mesh was fixed to the vaginal wall using non-absorbable sutures, and the anterior and posterior mesh pieces were then sutured together bilaterally to the cervical stump and uterosacral ligaments using non-absorbable sutures. Subsequently, the peritonea overlying the sacrum were dissected. The parietal end of one piece of mesh was then fixed to the sacral promontory using non-absorbable sutures. Peritoneal closure was performed above the mesh pieces using absorbable sutures (Monocryl; Ethicon). All reoperations for SUI were performed with a tension-free vaginal tape obturator (TVT-O).

Statistical analysis
Data were analyzed using EZR version 1.37 (http://www.jichi. ac.jp/saitama-sct/SaitamaHP.files/statmed.html) (Kanda 2013). Categorical variables and continuous variables are presented as the number (percentage) and the median (interquartile range), respectively. The Mann-Whitney U-test and Wilcoxon's signed rank test were used for continuous variables Fisher's exact test was used for categorical variables. Any reoperation and reoperation for some indications (POP recurrence, mesh-related complications, de novo or persistent SUI) were analyzed using the Kaplan-Meier method. In all analyses, p < 0.05 was taken to indicate statistical significance.

Results
A total of 200 patients underwent LSC for POP at our institute during the study period. Of these, 50 patients (25.0%) were lost to follow-up, 17 patients (8.5%) had a single mesh insertion, 2 patients (1.0%) died for reasons not related to the index surgery, and 12 patients (6.0%) did not complete the questionnaires. Therefore, the final study population consisted of 119 patients (Figure 1). Demographics and operative characteristics are presented in Table 1.
At 2 years after LSC, the subjective failure rate was 4.2% (5 of 119 patients) and the anatomical failure rate was 9.2% (11 of 119 patients). Of the 11 patients with anatomical failure in our study, 27.2% (3 of 11 patients) had subjective failure. Two of the five patients who underwent reoperations showed subjective failure. The remaining three showed subjective success. Two of the latter three cases underwent reoperation within 2 years, and the remaining one had a ring pessary inserted. The PFDI-20, POPDI-6, CRADI-8, UDI-6, and ICIQ-SF scores improved significantly after LSC in the group without subjective failure (Table S1). However, there were no significant differences in PFDI-20, POPDI-6, CRADI-8, UDI-6, and ICIQ-SF scores before and after LSC in the subjective failure group (Table S2). In addition, the differences in symptom scores from preoperatively to 2 years postoperatively were compared between the groups with and without subjective failure. Only the difference in POPDI-6 score was statistically significant between with two groups (p ¼ 0.04) (Table S3).
Anatomical failure was observed at a median of 12 months postoperatively in the 11 patients (9.2%) ( Table 2). Characteristics for reoperation are presented in Table 2 and Kaplan-Meier curves are shown in Figure 2. Any reoperations were required for 14 patients (11.7%). As one patient underwent repeat surgery three times, the total number of reoperations was 16 (13.4%). The median time to reoperation was 21 months.
Thirty-four patients (28.5%) complained of preoperative SUI, which had resolved at 3 months postoperatively in 15 of these patients (44.1%). Occult SUI was identified in five patients (4.2%), which had resolved at 3 months after LSC in three patients (60.0%). Fifteen patients (12.6%) developed de novo SUI after 3 months postoperatively, which had resolved at 2 years after LSC in 9 patients (60.0%). TVT-O was performed at 6 and 16 months after LSC in two (13.3%) of the six patients (40.0%) whose de novo SUI did not improve. Of the 34 patients with SUI preoperatively, 19 (55.8%) and 12 (35.2%) patients had persistent SUI at 3 months and 2 years   We encountered two very rare complications, i.e. urethral obstruction and small bowel obstruction at 47 and 42 months after index surgery, respectively. The patient with urethral obstruction underwent TVT-O concomitant with anterior vaginal wall colporrhaphy, followed by surgery for mesh-related complications, for a total of three reoperations. After sudden urinary retention, cystoscopy was performed and it was found that the tape had eroded through the posterior wall of the mid-distal urethra, so partial excision of the tape and repair of the urethrotomy was performed. The patient with small bowel obstruction had LSC with uterine preservation. Emergency laparotomy was performed, and intraoperative findings showed that a strip of Y-shaped mesh had penetrated the left broad ligament, causing a hole through which the small intestine had entered, resulting in small bowel obstruction.

Discussion
This study determined the medium-term subjective failure rate (4.2%) with PROs and anatomical failure rate (8.4%) after LSC. The slightly higher anatomical failure rate in comparison to the subjective failure rate observed in this study may reflect surgeon observations of asymptomatic stage 2 POP on examination. Our cohort had a low rate of reoperation (13.4%) after LSC. The most common reoperations were for SUI (7.5%), followed by POP recurrence (4.2%) and meshrelated complications (1.6%).
Sawada et al. (2021) reported a subjective failure rate of 10.3% and an anatomical failure rate of 9.4% at 3 years after LSC. We defined subjective failure as a sore of 2 (somewhat) or higher in question 3 of POPDI-6, whereas Sawada et al. used a definition of a score of 0 (not present) or higher, which may have caused the observed differences in the subjective failure rate between the two studies. Wagner et al. (2019) reported the long-term impact of LSC on pelvic symptoms and QOL based on PFDI-20. They reported the changes in PFDI-20 score over time (3, 12, 36, and 60 months), and showed that the improved scores were sustained during follow-up. A similar trend was observed in our study, although our data were collected at a single time point, 2 years after surgery. Generally, PROs use questionnaires that evaluate the distress caused by various symptoms and create consecutive scores that can measure differences among populations or within a population. It is important to note that the group with subjective failure did not show significant differences in any of the PFDI-20 components or the ICIQ-SF between preand postoperative comparisons.
Comparing the differences in questionnaires between the groups without subjective failure and those with failure before and up to 2 years after LSC, the POPDI-6 score showed a significant difference between the two groups (p ¼ 0.04). In the subjective failure group in the present study, pre-and postoperative the difference in POPDI-6 score was À 4.2. The definition of failure used in the present study was consistent with the definition of failing to meet the minimal important difference (MID) of À 11 in change in POPDI-6 score proposed by Karjalainen et al. (2021). PROs measure QOL based on a patient's self-reporting and perceptions of change (Bovbjerg et al. 2009). Interpretation of PROs may be an issue when determining what amount of change in a score is considered clinically meaningful. To deal with this issue, the concept of MID has been introduced to indicate the minimal change in score that a patient feels is important (Jaeschke et al. 1989).
In terms of POP recurrence, Sarlos et al. (2014) also reported the highest frequency of anterior wall recurrence at 8.8% over 5 years. In our study, the anterior wall was also the most common site of recurrence (4.2%), followed by the posterior wall (2.5%) and the apex alone (1.6%). However, recurrence at the anterior wall plus apex was also observed in 0.8% of cases. On the other hand, Wagner et al. (2019) Figure 2. Kaplan-Meier curves of the time to reoperation after LSC. One patient had undergone reoperations for SUI concomitant with POP recurrence reoperation, and eventually also underwent mesh-related reoperation for a total of three reoperations. POP: pelvic organ prolapse; SUI: stress urinary incontinence.
reported the highest frequency of posterior wall recurrence (19.7%) over 5 years. The differences in recurrence may have been because Sarlos et al. (2014) used a double mesh, whereas Wagner et al. (2019) used a double mesh only in cases of symptomatic rectocele and therefore used a single mesh in principle. The recurrence rate of the apex was 1.5% in the report of Sarlos et al. (2014) and 2.8% in that of Wagner et al. (2019). Our result was comparable to their long-term results, and the apex support was good. Moreover, the reoperation rate for POP recurrence was 4.2% in our study, which was similar to those reported by Sarlos et al. (2014;3.5%) and Wagner et al. (2019;5.3%).
Reoperation for SUI was required in 7.5% of cases. Giugale et al. (2019) reported that SUI was resolved postoperatively in nearly one third of women with preoperative SUI who underwent minimally invasive sacrocolpopexy, and persisted in the remaining two thirds of the patients. However, of women in whom SUI persisted, half were treated with delayed TVT-O, while half of the remaining women received pelvic floor physical therapy. Pizzoferrato et al. (2019) reported that LSC combined with SUI surgery was strongly associated with postoperative patient dissatisfaction. Based on their report, we chose delayed TVT-O in our patients.
We encountered two very rare complications, i.e. urethral obstruction and small bowel obstruction after index surgery. Pacqu� ee et al. (2019) reported a 7% rate of mesh-related complications in their long-term results, the majority of which were mesh exposures, but they also reported two cases of small bowel obstruction associated with periumbilical adhesions.
There was some bias in our study, including potential selection and observation bias, because this was not a randomized controlled trial. With regard to selection bias, only 59.5% of patients in our initial cohort were included in this study, with the other 40.5% lost to follow-up. Although observation bias is well recognized in observational retrospective studies, a major limitation of this study was that the investigators were not blinded and the survey was conducted by the attending surgeon. A major strength of our study was that we confirmed that patients who perceived vaginal bulge after surgery had not yet reached the MID in terms of POPDI-6 score difference before and after surgery, i.e. we showed that patients without improvement in their QOL with surgery also did not achieve MID.
In conclusion, this study established that most women had improved QOL at 2 years after LSC. We demonstrated that patients with persistent postoperative vaginal bulge also had no improvement in postoperative urinary and colorectal symptoms. The most common causes for reoperation were SUI (7.5%) and POP recurrence (4.2%) and not mesh-related complications (1.6%).