Questionnaire survey regarding current status of minimally invasive surgery for endometrial cancer in Japan: A cross‐sectional survey for JSGOE members

Minimally invasive surgery (MIS) has been introduced as an alternative to more radical surgical procedures. The Japan Society of Gynecologic and Obstetric Endoscopy and Minimally Invasive Therapy conducted a cross‐sectional questionnaire survey to ascertain the status of MIS for endometrial cancer.

67% of respondents did not use uterine manipulators, and 59% of the respondents did not perform lymph node dissection following the guidelines for treating endometrial cancer in Japan. Conclusion: This study provided the current status of MIS for endometrial cancer in Japan. The hysterectomy method, use of uterine manipulators, and criteria for omitting lymph node dissection were generally in agreement with the guidelines. Currently, an extra-fascial simple hysterectomy, including at least not shaving the cervix, was a major method for early invasive endometrial cancer using MIS.

INTRODUCTION
Endometrial cancer has rapidly increased in recent years and is the most common gynecologic tumor in developed countries. 1 Surgery is the primary treatment for endometrial cancer, and minimally invasive surgery (MIS), such as endoscopic surgery and robot-assisted surgery, has gained wide acceptance as alternatives to more standard surgical procedures. 2 In Japan, the percentage of MIS procedures for stage I-II endometrial cancer increased from about 30% in 2017 to about 40% in 2019. 3,4 The guidelines for the treatment of uterine body neoplasms (Japan Society of Gynecologic Oncology [JSGO] 2018 edition) state that laparoscopic surgery is recommended for patients with atypical endometrial hyperplasia or Stage I endometrial cancer who are at low risk of recurrence. 5 The guidelines also state that an abdominal total hysterectomy or extended total hysterectomy (extra-fascial) is recommended for stage I endometrial cancer cases as a specific surgical procedure. 5 A modified radical hysterectomy can be proposed depending on the situation, but an extra-fascial simple total hysterectomy is recommended as the principal method. 5 The guidelines do not distinguish a surgical procedure for removing the uterus between MIS and open surgery.
There are significant differences in the field of view during surgery, surgical procedures, and instruments used between MIS and open surgery. In addition, because most cases of early-stage endometrial cancer can be cured with surgery alone, many surgeries may be performed by physicians who have not received specialized training in gynecologic oncology surgery. It was not clear whether or not there was a difference in the surgical method due to the difference in the qualifications of specialized training in gynecologic oncology surgery. Therefore, the Japan Society of Gynecologic and Obstetric Endoscopy and Minimally Invasive Therapy (JSGOE) conducted a cross-sectional questionnaire survey among its members to determine the current status of MIS for endometrial cancer. The primary purpose of this questionnaire is to analyze MIS surgical procedures for endometrial cancer, and the secondary purpose is to analyze whether the presence or absence of various certifications is associated with surgical procedure selection.

METHODS
All procedures performed in this study involving human participants were in accordance with the ethical standards specified by the Institutional Research Committee and the 1964 Declaration of Helsinki and its subsequent amendments, or comparable ethical standards. This study was approved by the JSGOE Board of Directors prior to conducting the survey. Additionally, this study was approved by the Ethics Committee of Nippon Medical School Hospital (B-2023-647). Informed consent is not applicable in this study.
We distributed a cross-sectional questionnaire survey to JSGOE members regarding endoscopic surgery for endometrial cancer. The survey was completed between May 10 and June 30, 2022. The number of JSGOE members at the end of June 2022 was 4747, of whom 2686 (57%) were male and 2061 (43%) were female (Supplementary Table 1). The questionnaire and answer choices are shown in Table 1.
All data generated or analyzed during this study are included in this published article and its' Supporting Information files. The chi-square of Pearson or Fisher's exact test for proportion was used to analyze categorical or continuous data distribution. All p-values were two-sided, and differences with a p-value < 0.05 were considered statistically significant. Statistical analysis was performed using GraphPad Prism (version 5, San Francisco, CA).

RESULTS
The total number of respondents was 436 (9.2% of the membership). There were 332 male respondents (12.4% of all male members) and 104 female respondents (5% of all female members). The characteristics of the respondents are listed in Table 2. Among the respondents, 64% were board-certified gynecologic endoscopists (laparoscopists) of the JSGOE, and 60% were board-certified gynecologic oncologists of the JSGO ( Table 2). The number of members with both certifications was 162.
When asked about the number of MISs performed for invasive endometrial cancer, 68% of the respondents performed ≤10 cases (including no cases) per year ( Figure 1a). When asked to choose a hysterectomy method from among simple total hysterectomy (equivalent to benign surgery), simple total hysterectomy with caution not to shave the cervix, extended total hysterectomy, and modified radical hysterectomy, the percentages reported by respondents were 3%, 31%, 48%, and 15%, respectively (Figure 1b). An analysis of hysterectomies performed using MIS for uterine cancer by a Q12. With respect to hysterectomies, which of the following methods do you use to remove the uterus? 1) Simple total hysterectomy (whether or not the ureter is exposed is on a case-by-case basis, extra vaginal removal is not considered, and there may be some cervicovaginal shaving as a result) 2) Simple total hysterectomy (whether or not the ureter is exposed is on a case-by-case basis, but I am conscious of not shaving the cervicovaginal area) 3) Extended total hysterectomy (the ureter is detached from the retroperitoneum as little as possible, and the vaginal canal is cut and processed, making sure the ureter is in place, and I am conscious of not cutting more or less of the vaginal canal or the cervicovaginal area) 4) Semi-radical hysterectomy (the ureter is given dorsally, the parametrium is cut and processed, and I try to cut the vagina at least a few mm to 1 cm qualified gynecologist of endoscopy (laparoscopy) of the JSGOE, a board-certified gynecologic oncologist of the JSGO, and both showed a statistically significant tendency not to choose simple total hysterectomy compared to the group that did not hold a certification (p = 0.019, p = 0.045, and p = 0.010, respectively; Figure 2). Of the respondents, 67% indicated that they did not use uterine manipulators. Only a few respondents said they always used uterine manipulators, and when they did, many responders took precautions, such as inserting the uterine manipulator after the fallopian tubes were sealed ( Figure 3). Regarding the precautionary measures for tumor dissemination at the time of hysterectomy, 66% of the respondents placed the uterus in a collection bag at the time of removal, and 50% of the respondents closed the external uterine os with suture before surgery (Figure 4a). The most common response (59%) with respect to a uterus that could not be removed vaginally was to place the uterus in a collection bag and remove the uterus from the body through a small incision (Figure 4b). In the free-text section, a number of respondents indicated that if the uterus was too large to be removed transvaginally, conversion to open surgery was selected instead of MIS.
When asked about the criteria for omitting lymph node dissection, 59% of the respondents did not perform lymph node dissection for Grade 1 or 2 endometrial carcinoma with <1/2 myometrial invasion and a tumor diameter <2 cm or without myometrial invasion ( Figure 5), following the guidelines for treating endometrial cancer in Japan. Based on the responses, it was also clear that there were specific differences in attitudes among institutions.

DISCUSSION
We administered a questionnaire survey to determine the current status of MIS for endometrial cancer in Japan. The number of surgeries per facility or surgeon was much lower than in various reports. 6 The Japanese medical insurance system allows similar treatment in all areas without strict limitations on facilities and surgeons. This survey considered that the number of cases per surgeon is low in Japan because MIS for endometrial cancer is not centralized in high-volume centers compared to other countries. The lack of centralization is also thought to be one of the reasons for the variation in surgical methods among surgeons.
In Japan, a conventional laparotomy with a modified radical hysterectomy or an extended hysterectomy is the standard method for a hysterectomy in patients with endometrial cancer. 7,8 As laparoscopic surgery has become increasingly popular, some gynecologists have pointed out that the definition of the technique is ambiguous. In general, endometrial cancer has a higher early detection rate and better prognosis than other gynecologic malignancies, making it challenging to evaluate tumor outcomes based on different surgical methods. A trial comparing extra-fascial simple hysterectomy and modified radical hysterectomy for Stage I endometrial cancer (ILIADE study) concluded that modified radical hysterectomy was not superior to extra-fascial simple hysterectomy for local control. 9 Although the ILIADE trial included mostly open procedures and only a few minimally invasive procedures, a modified radical hysterectomy was considered acceptable if necessary to achieve adequate vaginal wall resection. 9 In the ILIADE study, the ureter was not isolated, the parenchyma was separated medial to the ureter and lateral to the cervix, the sacral and bladder uterine ligaments were separated near the uterus, and the vaginal wall attachment to the cervix was kept to a minimum as the definition of the extrafascial simple total hysterectomy technique. 9 The ureteral tunnel is opened during a modified radical hysterectomy, the ureter is rolled outward, the parenchyma is removed at the level of the ureteral tunnel, approximately 30% of the sacral and bladder uterine ligaments are removed, and the vaginal wall is removed with approximately 15-20 mm of attachment. 9 A review of the clinical trial hysterectomy protocols, which compared open versus MIS for endometrial cancer, revealed that the basic technique was an extra-fascial simple hysterectomy in the LAP2 study. 2  shaving the cervix. 10 In addition, a randomized trial in the Netherlands reported that the uterus was removed with a vaginal wall cutting on the rim of the vaginal tube without shaving the cervix. 11 The hysterectomy procedure was equivalent to an extra-fascial simple total hysterectomy in these clinical trials. In contrast, Malzoni et al. 12 conducted a prospective randomized trial comparing total laparoscopic hysterectomy and abdominal hysterectomy with lymphadenectomy for early-stage endometrial cancer using a more expanded hysterectomy method. The surgical procedure for a total laparoscopic hysterectomy in this study defined that the upper onethird of the vagina was visualized. 12 A 1-cm margin of the vaginal cuff around the cervix was transected with monopolar cautery, incising the vagina circumferentially using the porcelain valve of the uterine manipulator as a guide, 12 thus ensuring that the cervix was resected with a secure margin without shaving the cervix. The NCCN guidelines for uterine cancer state that a simple total hysterectomy with bilateral salpingooophorectomy is necessary for early-stage endometrial cancer. 13 A radical hysterectomy should be performed only if needed for Stage II patients to obtain negative margins. 13 The ESMO guidelines 14 and Korean guidelines 15 also state that a simple total hysterectomy with bilateral salpingo-oophorectomy is an essential technique for early-stage endometrial cancer. The Spanish 16 and British 17 guidelines recommended a simple total hysterectomy with bilateral salpingo-oophorectomy without vaginal cuff resection as the standard surgery for early-stage endometrial cancer. The ESGO guidelines also state that vaginal wall attachment to the cervix is usually superfluous. 18 More extensive techniques than total hysterectomy should only be used if required to achieve free surgical margins. 18 The survey on surgical methods in this questionnaire showed that simple total hysterectomy was used by approximately 30% of the respondents. In contrast, extended total hysterectomy and modified radical hysterectomy, which are methods to identify the ureter, were used by a combined total of approximately 60% of respondents. This finding may be attributed to the fact that laparotomy with identification of the ureter is the standard for uterine cancer surgery in Japan. 7,8 F I G U R E 1 Number of MIS cases and surgical removal methods for endometrial cancer. (a) How many laparoscopic procedures (including robotic-assisted) for endometrial cancer do you perform per year? (b) Regarding the hysterectomy method, which of the following methods would you use to remove the uterus?
With respect to uterine manipulators, the 2019 JSGOE guideline states that a uterine manipulator should be used cautiously during laparoscopic surgery for malignancies, 19 including endometrial cancer. Clipping or coagulating the fallopian tubes is required, even if used before insertion of the uterine manipulator. Multiple factors have been pointed out regarding the potential risks of using uterine manipulators for endometrial cancer. In addition to perforation of the uterine wall, tumor pressure drainage during the vaginal wall incision, cell dispersal into the fallopian tubes, and the risk of accelerated invasion into blood vessels and lymphatic vessels due to increased uterine lumen pressure has recently been noted. 20 A multicenter, retrospective cohort study compared oncologic outcomes with and without use of a uterine manipulator; recurrence and overall survival were significantly worse in the uterine manipulator group. 20 Another multicenter,  prospective, randomized trial compared oncologic outcomes with and without use of a uterine manipulator, and there were no significant differences between both groups. 21 In another randomized trial study comparing the use and non-use of a uterine manipulator for endometrial cancer, there was no difference in the positive rates of "ascites cytology" and "vascular invasion" and no impact on prognosis. 22 F I G U R E 5 Criteria for omitting pelvic lymph node dissection.
The limitation of this study is the small percentage of members who responded to the survey. This preliminary survey had 436 responders, with only 9.2% of all 4747 JSGOE members. Endoscopic surgery in the field of obstetrics and gynecology has a historical development that has focused primarily on the treatment of benign diseases such as ovarian cysts and endometriosis. According to the case registry reports of the JSGOE, more than 90% of the cases were for benign diseases. 23 It is estimated that a significant number of JSGOE members specialize in the management of benign gynecologic diseases, and most physicians do not routinely perform MIS for endometrial cancer. When limited to qualified endoscopic (laparoscopic) specialists of the JSGOE, 280 out of the 1215 eligible physicians (23%) responded. Hence the findings of this survey may not reflect the real situation in Japan as a whole. Another limitation was that the respondent's institutional affiliation was not included in the questionnaire. We intentionally did not ask about institutional affiliation in order to make the questionnaire anonymous so that individuals could not be identified. However, as a result, we could not obtain information on whether there were regional differences in responses. The results of our questionnaire analysis cannot be a reflection of the situation in Japan as a whole. Further research on a larger scale will be necessary in the future.
In conclusion, this study has provided an understanding of the current status of MIS for endometrial cancer in Japan. Although the number of surgeries per surgeon tended to be small, the method of hysterectomy and criteria for omitting lymph node dissection were generally in agreement with the JSGO guideline. 5 Currently, an extra-fascial simple hysterectomy is recommended as the principal surgical procedure for early endometrial cancer during MIS. Although some gynecologic oncologists had ever recommended to remove the vaginal wall by modified radical hysterectomy or extend hysterectomy, an extra-vaginal wall attachment or routine modified radical hysterectomy is not recommended in the latest guidelines. There is no solid evidence that using a uterine manipulator worsens the prognosis; however, some studies indicate the risk of using a uterine manipulator, and use of a uterine manipulator should be done with caution.