Outcome of robot-assisted surgery for stage IA endometrial cancer compared to open and laparoscopic surgeries: A retrospective study at a single institution

Background Few studies have compared the e�cacy of robot-assisted, laparoscopic, and open surgeries for endometrial cancer. When considering the position of robotic surgery in Japan, it was necessary to determine whether it was effective or not. We aimed to compare the e�cacy and safety of these three types of surgeries for early-stage endometrial cancer. Methods


Introduction
In 2009, the LAP2 trial demonstrated the e cacy of laparoscopic (LA) surgery for endometrial cancer [1].
A subsequent study reported the effectiveness of robot-assisted (RA) surgery for recurrent low-risk endometrial cancer [2].In Japan, LA surgery started being covered under insurance as a surgical treatment for early-stage endometrial cancer in 2014, and RA surgery started being covered in 2018.RA surgery is widely used in many facilities [3].This surgery is an option comparable to LA surgery, as it is a minimally invasive surgery (MIS) for early-stage endometrial cancer according to the National Comprehensive Cancer Network Guidelines (2017) [4].Compared with LA surgery, RA surgery has several advantages, including an expanded eld of view in the abdominal cavity, increased control of the camera by the surgeon, and few restrictions on the range of motion of the instruments.Furthermore, it is useful in gynecological surgery, including lymph node dissection and vaginal dissection suturing.Robot-assisted surgery is a feasible option for MIS as it signi cantly enhances a patient's quality of life [5].In fact, it has been reported to be comparable to conventional open surgery in terms of the oncological outcomes for endometrial cancer.Although there are several reports comparing RA, LA, and open surgery for endometrial cancer, there are few studies comparing the three types of surgery limited to early-stage cases [6,7].Therefore, we aimed to investigate the e cacy and safety of RA surgery for stage IA endometrial cancer performed at our hospital and demonstrate the superiority of RA surgery over other procedures.

Materials and methods
We included 175 patients with preoperative stage IA endometrial cancer (International Federation of Gynecology and Obstetrics) who underwent laparotomic (n = 80), LA (n = 40), or RA (n = 55) modi ed radical hysterectomy at our hospital between 2010 and 2022.In our hospital, we opted for LA from 2014 to 2016, RA from 2019 onward, and OP for the rest of the study period.For LA, we used the ve-port diamond method with a 12-mm camera port in the umbilicus and a 12-mm assist port on the left side of the abdomen.
We performed RA using the da Vinci X or Xi Surgical System (Intuitive Surgical Inc., Sunnyvale, CA, USA).
A camera port was placed 3 cm above the umbilicus, with the right lateral abdomen 6-7 cm and 12-14 cm from the camera port, and 12 cm to the left at the umbilical level from the camera port, and an assist port at 4.5 cm head vertically from the midpoint of the camera and the left port.Pelvic lymphadenectomy was performed in all patients in the OP and LA groups, and in 36 patients (65.4%) in the RA group.Since 2022, pelvic lymphadenectomy has not been performed for patients with stage IA endometrial cancer with tumors less than 2 cm in diameter and without myometrial invasion; hence, the number of patients who did not undergo pelvic lymphadenectomy has increased recently.We retrospectively compared the surgical outcomes, perioperative complications, and prognoses of the three techniques in patients who underwent pelvic lymphadenectomy.Furthermore, the total operative and console times of RA were investigated separately with or without pelvic lymphadenectomy.Perioperative complications were analyzed using the Clavien-Dindo (CD) classi cation.
All surgeries were performed by gynecologic oncologists certi ed by the Japanese Society of Gynaecologic Oncology.Additionally, LA and RA were performed by a gynecologic oncologist and LA surgeon certi ed by the Japanese Society of Obstetrics and Gynecology.

Statistical analysis
The Mann-Whitney U-test and Chi-square or Fisher's exact test were used to investigate the signi cance of the differences.For prognostic analysis, a survival curve was constructed using the log-rank test.
Statistical signi cance was set at P < 0.05.All statistical analyses were performed using the GraphPad Prism 8.3 software (GraphPad Software, Inc., La Jolla, CA, USA).
This study was approved by the Institutional Review Board of Tottori University Hospital (IRB no.

22A134
).All patients provided written informed consent following institutional guidelines.All methods were performed in accordance with relevant guidelines and regulations.

Results
Patients' clinical and pathological characteristics are shown in Table 1.Age and BMI did not differ among the three groups.The number of patients with postoperative advanced stage IA in the RA, LA, and OP groups were 50 (90.9%),33 (82.5%), and 71 (88.8%), respectively.There was no signi cant difference in the number of cases with positive ascites cytology or vascular invasion among the groups.The follow-up period was the longest for OP, followed by LA and RA.Comparison of the three types of surgeries for patients who underwent pelvic lymphadenectomy The surgical results of the patients who underwent pelvic lymphadenectomy are shown in Table 2 and Fig. 1.Among the patients who underwent pelvic lymphadenectomy, the total operative time was the shortest in the RA group, followed by that in the OP and LA groups.There was no difference in the estimated blood loss between the RA and LA groups, with a signi cant decrease compared with that in the OP group.The length of hospital stay was shortest in the RA group, followed by that in the LA and OP groups.The number of retrieved lymph nodes was the largest in the LA group, and there was no difference in the number of patients between the RA and OP groups.
The prognoses of the patients with advanced postoperative stage IA disease were compared.Progression-free survival (PFS) and overall survival (OS) did not differ among the three techniques; however, the PFS was shorter in the OP group (Fig. 2).No cases of recurrence were observed in the RA group.The frequency of complications (Grade 1 or higher CD classi cation) was 40.0%(32 patients), 35.0%(14 patients), and 16.7% (6 patients) in the OP, LA, and RA groups, respectively (p = 0.02) (Table 3).
A high incidence of wound infection and lower lymphedema was observed in the OP group.More than one complication occurred in three patients in the OP group (ileus and lower lymphedema, lymphocyst infection and venous thrombosis, abdominal wall hematoma, and external iliac vein injury).Furthermore, complications of Grade 2 or higher CD classi cations were observed in 6 patients (15.0%) in the LA and 15 patients (18.8%) in the OP group, with none in the RA group.

Total operative and console times for
Figure 3 shows the changes in the total operative and console times between patients who did and did not undergo pelvic lymphadenectomy.The total operative and console times reduced with each experience in cases of RA with and without pelvic lymphadenectomy, and the learning curve was reached after 10 cases each (approximately 20 cases in total).

Discussion
In this study, RA surgery, performed at a single center by the same surgeon, showed a shorter total operative time, less blood loss, and shorter hospital stay than those shown by open surgery.RA surgery also showed a shorter operative time and trend toward a reduced length of hospital stay than those shown by LA surgery.The frequency of complications was the lowest in RA surgery and did not differ between LA and open surgeries.No complications occurred with RA surgery, at least in patients aged > 61 years.These results suggest that RA surgery is less invasive and more effective than open or LA surgery in the treatment of early-stage endometrial cancer.
Reports on the advantages of RA surgery for endometrial cancer have increased in recent years.
Regarding the learning curve, in one study, the operative time was shorter and complications were fewer in procedures using a robotic system than those in procedures not using it [8].In our study, the total operative time signi cantly decreased as the surgical experiences increased.Prior studies comparing open and LA surgery with pelvic lymphadenectomy for endometrial cancer also indicated that the learning curve for RA surgery can be achieved after a few cases [9,10].In these studies, the learning curve was achieved after approximately 20 cases, similar to the nding in our study.Thus, our results are comparable to those reported previously, and the accuracy of our surgical outcomes is worthy of consideration.
Robot-assisted surgery is associated with early discharge because of the low frequency of postoperative pain.Naixin et al. investigated the safety of same-day discharge of patients who underwent RA surgery for endometrial cancer [11].They reported that over 80% of the patients were discharged on the day of surgery with several criteria met, including oral intake, ambulation, and postoperative Hb levels (decrease of 2 g/dL or less from baseline), and only 1.3% of the patients visited the emergency department within 30 days after surgery.In our study, many patients were discharged on the fth postoperative day, but discharge may have been possible on the third or fourth day.However, we believe that for early discharge, it is essential to have an environment in which patients can receive medical care if any symptoms appear, as well as su cient discharge guidance.This point is important because medical insurance systems differ among countries.
In elderly patients, open surgery is associated with an approximately 2.5-fold higher perioperative complication rate than that associated with RA surgery [12].Antonio et al. reported that the risk of perioperative complications with RA surgery for endometrial cancer decreases as the patient's age increases.In the present study, perioperative complications were frequently observed among patients in the open surgery group, but none were observed even among patients aged over 61 years in the RA surgery group.Elderly patients often have comorbidities, with a high risk of requiring surgery and anesthesia.Therefore, MIS is increasingly being used in this patient population.In one study comparing LA and RA surgery for elderly patients with endometrial cancer, there was no difference in perioperative complications between the two groups [13]; however, in our study, perioperative complications were less frequently observed in the RA group than those in the LA surgery group.In RA surgery, the abdominal wall is lifted when the robotic arm is connected, allowing for a lower insu ation pressure than that allowed by LA surgery.Therefore, compared with LA surgery, RA surgery is useful not only for obese patients but also for elderly patients because its effect on cardiac output and respiratory motion owing to increased abdominal pressure can be reduced with it.In Japan, the aging society is expected to progress in the future, and the reduction in complications due to RA surgery is considered to be bene cial not only to patients but also to the medical economy.
There are several limitations to this study.First, the single-center setting of this study may have introduced a bias; further, the skills of the surgeon could also have in uenced our results.However, our results are comparable to those reported previously; therefore, the data can be considered generalizable.Second, there is the variable follow-up between the three groups.This is inevitable given that the different surgical techniques were used at different time points.Third, the sample size was small.Since large-scale data analyses are needed in Japan, data of registration projects need to be analyzed by relevant academic societies.

Figures
Figures

Figure 1 Comparison 2 3
Figure 1 Outcome of robot-assisted surgery for stage IA endometrial cancer compared to open and laparoscopic surgeries: A retrospective study at a single institution

Table 2
Surgical results of the patients who underwent pelvic lymphadenectomy *p-values robotic versus laparoscopic, robotic versus open, laparoscopic versus open surgeryRobot: robot-assisted surgery, Laparoscopy: laparoscopic surgery, Open: open surgery, SD: standard deviation

Table 3
Regarding the occurrence of complications with Grade 1 or higher CD classi cations, there were no cases of complications among patients aged over 61 years in the RA group; however, complications were frequently observed in the OP group (11/23 cases, 47.8%).In contrast, the 19 patients with RA who had not undergone pelvic lymphadenectomy had no perioperative complications.