Effect of modified radical laparoscopic hysterectomy versus open radical hysterectomy on short-term clinical outcomes in early-stage cervical cancer: a single-center, prospective, randomized controlled trial

Trial design

This study was a single-center, phase 2, randomized controlled trial registered under Chinese clinical trial number ChiCTR2000030160. Data was gathered from patients with FIGO (2018) stage IA1 (lymphovascular invasion), IA2, and IB1 cervical cancer at Zhongda Hospital of Southeast University in Nanjing, China, between March 2020 and July 2021. The institutional review board evaluated and approved relevant medical ethics issues (ethical approval number 2020ZDSYLL106-Y01). The study design flowchart is shown in Fig. 1.

Fig. 1figure 1

Laparoscopic vaginal stump closure using the endocutter

Sample size

The sample size was calculated according to the method specified in the previous study [11]. The 4.5-year DFS rate of patients undergoing radical hysterectomy for abdominal cervical cancer is estimated to be 90%. The selected non-inferiority margin is 15.0%. If the difference in disease-free survival rate is less than 15.0%, the two methods will be considered equivalent. The sample size required to evaluate the 4.5-year disease-free survival difference level was 70, the statistical power was assumed to be 80%, and the two-tailed test was 5% significant.

Trial conduct and oversight

Patients who met the following criteria were included in the study: (1) FIGO2018 stage IA1 (with vascular tumor thrombus), IA2, IB1; (2) the largest tumor diameter < 2 cm (MRI evaluation or pathological evaluation after conization < 2 cm); (3) histological types: squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma, except endometrioid adenocarcinoma; (4) patients with appropriate bone marrow hematopoietic function and renal function; (5) liver function: ((1) white blood cell count > 3.0 × 109cells/L; (2) platelet count > 100 × 109/L; (3) creatinine < 180 µmol/L; (4) bilirubin < 1.5 times normal, aspartate aminotransferase/alanine aminotransferase < 3 times normal); (6) Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1; (7) patients with surgical indications; (8) BMI < 35; (9) age range 18 to 70 years old; (10) patients who signed the informed consent.

Patients with the following conditions were excluded: (1) mental illness; (2) heart, liver, or kidney dysfunction; (3) bladder dysfunction before the operation or patients with other serious complications who could not bear the risk of surgery; (4) patients who had received radiotherapy or chemotherapy; (5) pregnant patients; (6) lost to follow-up; (7) tumor diameter ≥ 2 cm; imaging evaluation showing that the cervical tumor invades the outer 1/3 of the stroma or involves the lower uterine segment; (8) patients with FIGO stage IB2 and above; (9) patients whose medical compliance and geographic location could not guarantee sufficient follow-up; (10) patients with surgical contraindications; (11) BMI ≥ 35.

After signing a written consent, patients were randomly assigned by a network-based computer randomization program into the laparoscopy group and the laparotomy group at a ratio of 1:1. Masking was impossible because of the nature of the treatment.

All patients underwent extensive hysterectomy and pelvic lymph node dissection (with or without bilateral adnexectomy). The primary study objective was to compare the clinical outcomes between the laparoscopic group that used the endocutter stapler for vaginal stump closure and the laparotomy group that used right-angled forceps to close the vaginal stump. The primary outcomes of interest included the patients’ perioperative observation indicators and short- and long-term period complications. Recurrence and overall survival were considered secondary outcomes. The primary endpoint is 4.5 years of post-operative DFS (the time interval from the surgery date to the first recurrence).

Surgical procedure

Following the induction of general anesthesia, the patient was placed in the lithotomy position, then disinfected and draped before access into the abdominal cavity was obtained.

The laparoscopic group had four surgical incisions on the patient’s abdominal wall: (1) a 10-mm camera port in the umbilicus, (2) a 5-mm port at the McBurney’s point on the right side, (3) an identical 12-mm working port on the left lateral lower quadrant, and (4) a 5-mm port parallel to the left mid-clavicular line 2 cm laterally at the level of the umbilicus. Abdominal pressure was set to 12 mmHg. The patients were adjusted to approximately 30° of Trendelenburg position. After entering the abdominal cavity, we carefully explored the pelvic and abdominal cavities to rule out peritoneal dissemination or distant metastasis. We adopted the no-lifting technique described in earlier investigations [12] instead of using a uterine manipulator.

Subsequently, pelvic lymphadenectomy was performed, and para-aortic lymph node dissection was performed where necessary. Pelvic lymph nodes were resected en bloc according to the order of common iliac → external iliac → deep inguinal → obturator → internal iliac vessels. After dissecting one side of the lymph nodes, it was bagged and sealed in time. The wound was repeatedly rinsed with sterile water for injection, and the contralateral lymph nodes were treated similarly.

Following the radical hysterectomy, the Ethicon Johnson & Johnson Echelon Flex Powered Plus Long Articulating Endoscopic Linear Cutter (Endocutter) with two rows of triple staggered titanium staples were inserted through the 12 mm trocar port. The angle between the jaws of the endocutter and the vagina’s longitudinal axis was adjusted to 90°, and then about 3 cm of the upper part of the vagina was closed after ensuring there was no abnormal tissue in the jaws except for the vaginal tissue. After the endocutter is fired, the device’s staples are released, and the vaginal stumps are sewn together on both sides while simultaneously cutting the vaginal wall (Fig. 1). The vaginal stump and row of staples were then resected, and the pneumoperitoneum was closed. After the uterine specimen was extracted through the vagina, the pelvic and abdominal cavities were lavaged with water for injection, and the washing liquid was sent for examination. The vaginal stump was then sutured with a 2/0 barbed suture, and the uterus specimen and vaginal stump were submitted for a histopathology examination.

In the ORH group, the patient was placed in the lithotomy position following induction of general anesthesia. A mid-line incision of 20 cm was made on the lower abdomen, and the rest of the procedure was carried out as stated in a previous detailed report [13]. Right-angle forceps were used to circularly excise the upper segment of the vagina at about 3 cm, and the pelvic and abdominal cavities were lavaged before the vaginal stump was sutured, and the washing fluid was submitted for a histopathology examination.

Observation indicators

The patient’s general clinical and pathological information, such as age, body mass index, ECOG score, tumor grade, and pathological type, were recorded. Perioperative indexes include operation time (minutes), hospital stay (days), intraoperative complications (bleeding, major organ damage), intraoperative blood transfusion, lymphatic dissection, and the time to removal of the urinary catheter and drainage tube as well as the time spent dealing with the vaginal stump during the operation was recorded. Patients had regular follow-ups of their clinical condition, short-term post-operative indexes, post-operative complications, and pelvic lavage fluid cytopathology results were reviewed. Intraoperative complications, including bowel, bladder, ureter, nerve, or vascular injury, were considered short-term post-operative indexes. Early post-operative complications refer to vaginal stump infection and dehiscence within four weeks after surgery; long-term post-operative complications refer to incisional hernia and vaginal stump recurrence after 6 months.

Statistical methods

The SPSS 22.0 software was used for the statistical analysis. Continuous data were analyzed using a t-test, and the categorical data were analyzed using the χ2 test. The Yates correction test was applied if the conditions were not met. A two-sided P-value < 0.05 indicated statistical significance. Descriptive statistical analysis was used for treatment-related adverse events; disease-free survival and median survival time were estimated using the Kaplan–Meier method. Disease-free survival was calculated from the surgery date to recurrence or the last follow-up time. The survival time was calculated from the time of diagnosis to the end of the follow-up period or time of death following diagnosis.

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