Incidence of adverse events in minimally invasive versus open radical hysterectomy in early cervical cancer: Results of a randomized controlled trial

Abstract

Background

Standard treatment of early cervical cancer involves a radical hysterectomy and retroperitoneal lymph node dissection. The existing evidence on the incidence of adverse events following minimally invasive versus open radical hysterectomy for early cervical cancer is either non-randomized or retrospective.

Objective

To compare the incidence of adverse events following minimally invasive versus open radical hysterectomy for early cervical cancer.

Study Design

The Laparoscopic Approach to Carcinoma of the Cervix (LACC) trial was a multinational, randomized non-inferiority trial conducted between 2008 and 2017, in which surgeons from 33 tertiary gynecological cancer centers in 24 countries randomized 631 women International Federation of Gynecology and Obstetrics 2009 stage IA1 with lymph-vascular invasion to IB1 cervical cancer to either minimally invasive versus open radical hysterectomy. Patients were randomly assigned to undergo minimally invasive (n = 319) or open radical hysterectomy (n = 312). The LACC trial was suspended for enrolment in September 2017 due to an increased risk of recurrence and death in the minimally invasive surgery group. Here we report on a secondary outcome measure, the incidence of intra and postoperative adverse events within 6 months after surgery.

Results

Of 631 patients randomized, 536 (85%) (mean age, 46.0 years) met inclusion criteria for this analysis; 279 (52%) underwent minimally invasive radical hysterectomy, and 257 (48%) underwent open radical hysterectomy. Of those, 300 (56%), 91 (16.9%), 69 (12.8%) experienced at least one grade 2+, grade 3+, or a serious adverse event. The incidence of intraoperative grade 2+ adverse events was 12% (34/279 patients) in the minimally invasive versus 10% (26/257) in the open group (difference; 2.1% (95% CI: −3.3%, 7.4%); p=0.45). The overall incidence of postoperative grade 2+ adverse events was 54% (152/279 patients) in the minimally invasive versus 48% (124/257) in the open group (difference; 6.2% (95% CI: −2.2%, 14.7%); p=0.14).

Conclusions

For early cervical cancer, the use of minimally invasive compared with open radical hysterectomy resulted in a similar overall incidence of intraoperative or postoperative adverse events.

Introduction

An estimated 570,000 women worldwide are diagnosed with cervical cancer each year.¹ In the United States, cervical cancer is the third most common gynecological malignancy, with an estimated 13,170 cases and 4,250 deaths anticipated in 2018.² The standard treatment recommendation for women with early cervical cancer is radical hysterectomy with pelvic lymph node dissection.³ Previous evidence from retrospective and non-randomized studies showed that minimally invasive radical hysterectomy was associated with better surgical outcomes than open radical hysterectomy, including less intraoperative blood loss, shorter length of hospital stay, less postoperative morbidity, and faster functional recovery.^4–7

The Laparoscopic Approach to Carcinoma of the Cervix (LACC) trial was a prospective randomized trial comparing open versus minimally invasive radical hysterectomy in patients with early cervical cancer. The primary aim was to compare disease-free survival between the two groups.⁸ The investigators found that minimally invasive radical hysterectomy was associated with lower rates of disease-free survival, higher rates of recurrence, and lower overall survival compared with the open approach.⁸

Before the LACC trial, no adequately powered, prospective randomized trial had evaluated the incidence of adverse events by surgical technique in patients with early cervical cancer undergoing radical hysterectomy. A secondary aim of the LACC trial was to compare intraoperative and postoperative adverse events in patients with early cervical cancer undergoing minimally invasive versus open radical hysterectomy. Here, we report the results of that analysis.

Materials and Methods

The LACC trial was an investigator-initiated phase III, multicenter, open-label, randomized controlled trial with the primary objective to evaluate the hypothesis that laparoscopic or robotic radical hysterectomy was non-inferior to abdominal radical hysterectomy (“open radical hysterectomy”) in terms of the proportion of patients’ disease free 4.5 years after surgery (clinicaltrials.gov identifier NCT00614211). Secondary objectives included comparing the two groups with regard to treatment-related morbidity, costs, quality of life, and pelvic floor symptoms.

The trial design, patient characteristics, and detailed inclusion and exclusion criteria were previously published.⁹ In brief, patients had to have histologically confirmed primary squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix; have International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA1 disease with lymph-vascular invasion, stage IA2 disease, or stage IB1 disease; and undergo a type II or type III radical hysterectomy.¹⁰ Pregnant patients were ineligible. Ethics approvals were obtained from the relevant Human Research and Ethics Committees at each participating center. Written informed consent was obtained from patients before randomization.

Each participating center was required to achieve accreditation by the Trial Management Committee to ensure proper surgical technique during minimally invasive surgery and to minimize the impact of any initial learning curve on the study results. All participating centers were required to submit treatment outcomes of 10 cases of laparoscopic or robotic radical hysterectomy and lymph node dissection. Then, if the outcomes were deemed appropriate, centers had to submit two unedited videos of a type III (Piver-Rutledge classification¹⁰) laparoscopic or robotic radical hysterectomy for accreditation.

Randomization and masking

Randomization was done centrally and independently of other study procedures through a web-based system at the University of Queensland, ensuring concealment of the next allocated treatment from study staff. Patients were randomized 1:1 in permuted blocks (mixed blocks of three and six patients). Randomizations were stratified according to treating center, clinical disease stage per the 2009 FIGO guidelines, and patient age (≤70 years or >70 years). Masking was not possible because of ethical considerations and the nature of the treatment.

Surgical technique and intraoperative and postoperative assessments

The techniques for open and for laparoscopic or robotic radical hysterectomy have been described in detail previously.^4,11,12 From here on, laparoscopic surgery and robotic surgery are referred to as minimally invasive surgery.

Intraoperative blood loss was estimated in milliliters and calculated as the total volume of suctioned blood minus the volume of irrigation fluids during surgery. The criteria for blood transfusion were left to the discretion of the surgical team. After surgery, patients were assessed for adverse events, concomitant illnesses and medications by history taking and clinical examinations. These assessments were repeated at 6 weeks, 3 months, and 6 months after surgery. Imaging and/or blood tests were requested only if clinically indicated. At each visit, any adverse events were documented.

An adverse event was defined as any untoward medical occurrence in a patient enrolled, regardless of its causal relationship to the study treatment. Any adverse events were recorded prospectively by trial staff, categorized and graded by severity using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE).¹³ Basic definitions of the CTCAE Version 3 are provided in supplementary table 1. An early postoperative adverse event was defined as any grade 2 or higher (2+) adverse event occurring up to 6 weeks after hysterectomy. A delayed postoperative adverse event was defined as any grade 2+ adverse event occurring 3 to 6 months after surgery. A serious adverse event was defined as any adverse event that required inpatient hospitalization or prolongation of an existing hospitalization, resulted in persistent or significant disability or incapacity, was life-threatening, or resulted in death. A major adverse event was defined as any CTCAE grade 3+ adverse event or a serious adverse event as described earlier in this paragraph.

Early closure

The study was suspended to new patient accrual in June 2017 owing to a statistically significant imbalance in safety events between the treatment groups. The study was stopped on the advice of the Data and Safety Monitoring Committee after 636 patients had been randomized, of whom 631 patients enrolled between June 2008 and June 2017 at 33 centers worldwide met the eligibility criteria. Oncological outcomes were reported previously.⁸

Statistical analysis

The main aim of the trial was to show non-inferiority with regards to survival outcomes. The trial was not powered to detect differences in complication rates. To be included in this analysis, patients had to have undergone surgery and had to have undergone follow-up assessments for adverse events for at least 6 months. All analyses were based on treatment received.

Baseline demographics were summarized in terms of frequency. Outcomes of interest were any grade 2+ adverse events, intraoperative adverse events, early and delayed postoperative adverse events, serious adverse events, major adverse events, length of hospital stay, length of operation, and blood loss. Categorical outcomes were summarized in terms of frequency and were compared between surgical techniques using a chi-square test. Adverse events have been summarised in three ways: Overall (Table 3); by organ systems of interest; and by specific adverse events of interest (Figures 1 and 2). For all analyses, adverse events have not been treated as mutually exclusive, and patients will be included in all appropriate summaries. In each case, the numerator was the number of patients who had experienced the AE being described, the denominator is the total number of patients (per arm).

Table 3.

CTCAE^a grade 2 or greater adverse events by surgical technique

Adverse event	Open surgery n=257(%)	Minimally invasive surgery n=279(%)	Difference (MIS - Open) (95% CI)	p value
Any adverse event	136 (53)	164 (59)	5.9% (−2.5%, 14.3%)	0.17
Intraoperative adverse event	26 (10)	34 (12)	2.1% (−3.3%, 7.4%)	0.45
Postoperative adverse event	124 (48)	152 (54)	6.25 (−2.2%, 14.7%)	0.14
Early postoperative adverse eventc	103 (40)	120 (43)	2.9% (−5.4%, 11.3%)	0.49
Delayed postoperative adverse eventc	52 (20)	70 (25)	4.9% (−2.2%, 11.9%)	0.18
Major adverse eventd	41 (16)	50 (18)	2.0% (−4.4%, 8.3%)	0.54
Serious adverse evente	30 (12)	39 (14)	2.3% (−3.3%, 8.0%)	0.43

^aCTCAE, Common Terminology Criteria for Adverse Events, version 3.0.

^bData are number of patients (percentage) unless otherwise indicated.

^cEarly, occurring up to 6 weeks after surgery; delayed, occurring 3 to 6 months after surgery.

^dAny CTCAE grade 3 or greater adverse event or a serious adverse event as defined below.

^eAn adverse event that required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, was life-threatening, or resulted in death.

Figure 1: Percentage of Patients with a CTCAE grade 2 or greater intraoperative adverse events by surgical technique.

Key for Figure 1

CTCAE, Common Terminology Criteria for adverse events, version 3.0;

MIS, minimally invasive surgery;

Open, open surgery.

Figure 2: Percentage of Patients with a CTCAE grade 2 or greater postoperative adverse event.

Key for Figure 2

CTCAE, Common Terminology Criteria for adverse events, version 3.0;

MIS, minimally invasive surgery;

Open, open surgery.

Where appropriate, a log-transformation was applied to non-normally distributed continuous variables. Continuous variables were summarized in terms of mean (standard deviation [SD]) and range and were compared between surgical techniques using a t-test. A Mann-Whitney test was used to compare length of hospital stay between surgical techniques.

In a subgroup analysis, the outcomes of interest were described in terms of frequency by minimally invasive technique (laparoscopic vs. robotic) but not formally compared. Logistic regression analysis was used to investigate the association of baseline patient and disease characteristics and surgical technique with any grade 2+ adverse events. All analyses were conducted in SAS version 9.3.

Results

Of the 636 patients randomized, 631 met the eligibility criteria, and 536 (85%) had all information available for this analysis; of those, 279 (52%) underwent minimally invasive and 257 (48%) underwent open radical hysterectomy. Fifty-eight patients were excluded as they did not undergo surgery, of whom 31 withdrew before surgery and 27 had their surgery abandoned. An additional 37 patients were excluded owing to missing data; two patients had incomplete data at the 6-week follow-up, and 35 had incomplete data at both the 3-month and 6-month follow-ups.

Ten patients switched treatment group before surgery, eight to minimally invasive and two to open surgery. Ten patients underwent a conversion from a minimally invasive to an open approach during the procedure, because of poor visualization of anatomy in five patients, intraoperative bleeding in two patients, equipment failure in two patients, and prolonged operative time in one patient.

The mean age of the 536 patients included in this analysis was 46.0 years. The mean body mass index was 26.7 kg/m², and 491 patients (92%) had stage IB1 disease. A total of 376 patients (70%) had squamous cell carcinoma. The two treatment groups were similar with regard to age, body mass index, ECOG performance status, stage, and histologic cell type (Table 1).

Table 1.

Baseline demographic and clinical characteristics and histopathology by surgical technique

Characteristic	Open surgery n=257(%)	Minimally invasive surgery n=279 (%)
Age at randomization, mean (SD), years	45.8 (10.4)	46.2 (10.9)
Weight, mean (SD), kg	66.3 (14.6)	68.5 (15.1)
Height, mean (SD), cm	158.2 (7.5)	159.5 (6.9)
Body mass index, mean (SD), kg/m2	26.5 (5.5)	26.9 (5.5)
ECOG performance status grade, n (%)
0	236 (92)	256 (92)
1	21 (8)	23 (8)
Stage, n (%)
IAI (with LVSIa)	4 (2)	5 (2)
IA2	18 (7)	16 (6)
IB1	235 (91)	258 (92)
Histologic cell type, n (%)
Adenocarcinoma	69 (27)	81 (29)
Squamous cell carcinoma	183 (71)	193 (69)
Adenosquamous carcinoma	5 (2)	5 (2)

^aLVSI, lymph-vascular space invasion

Perioperative outcomes

The mean duration of surgery was 216 minutes (range 75–441) for minimally invasive surgery and 187 minutes (range 61–425) for open surgery (Table 2). The mean estimated blood loss was 101 mL (range 10–1500) for minimally invasive surgery and 209 mL (range 10–2200) for open surgery (p<0.001) (Table 2). Intraoperative and/or postoperative blood transfusions were administered to 10 (3.6%) of 279 patients in the minimally invasive surgery group and 20 (7.8%) of 257 in the open surgery group (p=0.03). Overall, 14 patients received blood transfusions after surgery (mean time after surgery [SD] 3.38 days [3.2], range 0–22 days). Median length of hospital stay was 3 days (range 0–72) for minimally invasive surgery and 5 days (range 1–69) for open surgery (Table 2).

Table 2.

Perioperative outcomes by surgical technique

Surgical outcome	Open surgery n=257(%)	Minimally invasive surgery n=279(%)	p value
Length of surgery, geometric mean (range), min	187 (61.0–425.0)	216 (75.0–441.0)	P<0.001
Estimated blood loss, geometric mean (range), ml	209 (10–2200)	101 (10–1500)	p<0.001
Length of hospital stay, median (range), days	5 (1–69)	3 (0–72)	P=0.002

The mean estimated blood loss was 91 mL (range 10–500) for robotic surgery and 103 mL (range 0–1,500) for laparoscopic surgery. The mean length of surgery was 288 minutes (range 140–441) for robotic surgery and 205 minutes (range 75–420) for laparoscopic surgery. Median length of hospital stay was 2 days (range 0–34) for robotic surgery and 4 days (range 0–72) for laparoscopic surgery (Table 2).

Adverse events

Of the 536 patients, 300 (56%) experienced at least one adverse event, 91 (16.9%) experienced at least one major adverse event, and 69 (12.8%) experienced at least one serious adverse event (Table 3). The percentage of patients in the minimally invasive versus the open surgery groups was similar with respect to any adverse events, major adverse events, and serious adverse events (Table 3). Adverse events occurred in 71% (29 of 41) of patients in the robotic surgery group versus 57% (135 of 238) of patients in the laparoscopic surgery group.

Intraoperative adverse events

Sixty (11%) of the 536 patients had at least one intraoperative adverse event (Table 3). There was no difference in the percentage of patients who developed intraoperative adverse events(Figure 1). Intraoperative adverse events occurred in 10% (4 of 41) of patients in the robotic surgery group and 13% (30 of 238) of patients in the laparoscopic surgery group.

Postoperative adverse events

The percentages of patients with at least one early postoperative, delayed postoperative, major, and serious adverse events were similar between the minimally invasive and open surgery groups (Table 3).

Four (1.4%) of 279 patients in the minimally invasive surgery group and 16 (6%) of 257 in the open surgery group had wound complications (difference: −4.8% (95% CI: −8.1%, −1.5%); p=0.004); 11 (4%) of 279 patients in the minimally invasive surgery group and 2 (0.8%) of 257 in the open surgery group had vaginal vault complications (difference: 3.2% (95% CI: 0.6%, 5.7%); p=0.01); and 2 (0.7%) of 279 patients in the minimally invasive surgery group and 10 (4%) of 257 in the open surgery group had cardiac complications (difference: −3.2% (95% CI: −5.7%, −0.6%); p=0.02) (Figure 2, Supplementary table 2). Cardiac complications included: bradycardia, arrythmia, hypertension, postural hypotension, sinus and supraventricular tachycardia, postinfarct angina.

Risk factors

Increased body mass index was associated with an increased risk of any grade 2+ adverse event (odds ratio 1.05, 95% CI 1.01–1.08, p=0.007) (Table 4). Patient age, surgical technique, ECOG performance status, stage, and tumor size were not associated with the risk of adverse events. There was no statistically significant interaction between treatment group and obesity, suggesting that the effect of treatment on the incidence of adverse events did not differ between the obesity groups (data not shown).

Table 4.

Association of baseline demographic characteristics with any postoperative CTCAE^a grade 2 or greater adverse event

Characteristic	Odds ratio (95% CI)	p value
Age at randomization, years	1.00 (0.99, 1.02)	0.88
Body mass index, kg/m2	1.05 (1.01, 1.08)	0.007
Surgical technique, minimally invasive vs. open	1.27 (0.90, 1.79)	0.17
ECOG performance status grade, 1 vs. 0 Stageb	1.42 (0.75, 2.68)	0.29
IA2 vs. IA1 (LVSI)	1.01 (0.23, 4.45)	1.00
IB1 vs. IA1 (LVSI)	1.02 (0.27, 3.83)
Tumor size, > 2 cm vs. < 2 cm	0.98 (0.45, 2.12)	0.95

^aCTCAE, Common Terminology Criteria for Adverse Events, version 3.0.

^bFIGO 2009 staging. LVSI; lymph-vascular space invasion

Outliers

The proportion of patients who experienced at least one G2+ adverse event was evaluated on a site-by-site basis. There is no pattern amongst the sites indicating that some sites might be ‘outliers ‘(data not shown)

Comment

Principal Findings

In the LACC randomized trial, we found no difference in the overall incidence of intraoperative or postoperative adverse events between minimally invasive and open radical hysterectomy for early cervical cancer. The incidence of wound complications and cardiac events were significantly higher in the open group while vaginal vault complications were significantly higher in the minimally invasive group. Being overweight or obese was a risk factor for the development of adverse events.

Results

Several meta-analyses have been published comparing surgical outcomes of robotic, laparoscopic, and open radical hysterectomy for early cervical cancer.^5–7,14 All of the studies contributing to the meta-analyses were either retrospective or non-randomized, prospective case series.

Four meta-analyses comparing laparoscopic with open radical hysterectomy and including 10,698 patients concluded that laparoscopic radical hysterectomy is associated with less estimated blood loss, shorter hospital stay, and a longer operating time.^5–7,14 Furthermore, all four studies showed that while the risk of intraoperative complications was similar for the two surgical approaches, the risk of postoperative complications was higher with open than with minimally invasive radical hysterectomy.^5–7,14 Cao and colleagues compared postoperative complications in 22 studies including 2,922 patients who had laparoscopic or open radical hysterectomy for cervical cancer stages IA1 to IIB and reported a risk reduction of 25% in favor of laparoscopic surgery.⁵ Zhao and colleagues included 23 studies including 4205 patients with stage IB to IIA cervical cancer. There was no difference in the risk of deep vein thrombosis, lymphocele, lymphedema, and urinary tract infections between laparoscopic and open radical hysterectomy but the risk of ileus was lower and the time to open bowels was shorter in the laparoscopic group.⁷ Wang and colleagues analyzed 11 studies comparing 754 patients who had laparoscopic radical hysterectomy and 785 patients who had open radical hysterectomy for cervical cancer stage IA1 or IIA2 and reported a 54% reduction in the risk of postoperative complications in favor of laparoscopic surgery.⁶ Jin and colleagues conducted a network meta-analysis that included 17 studies on patients with stage I and II cervical cancer who had laparoscopic, robotic, or open radical hysterectomy and concluded that patients who underwent open radical hysterectomy had worse outcomes than patients who underwent minimally invasive surgery. Patients who had robotic radical hysterectomy experienced the lowest incidences of intraoperative and postoperative complications.¹⁴

Three additional meta-analyses compared surgical outcomes of robotic versus open radical hysterectomy for early cervical cancer.^15–17 Nevis and colleagues compared morbidity outcomes of patients with cervical cancer (35 observational studies) during 2009–2014. Perioperative outcomes and intraoperative complication rates were similar between robotic and laparoscopic and between robotic and open radical hysterectomy. The authors concluded that the quality of evidence for all reported outcomes was “very low” according to the GRADE evidence profile.¹⁵ Shazly and colleagues reviewed 26 studies that included 4,013 patients. These authors found that compared to open surgery, the robotic approach was associated with lower estimated blood loss, longer operating time, and shorter length of hospital stay. The incidence of intraoperative complications was similar for robotic, laparoscopic, and open surgery, whereas the incidence of postoperative complications was lower for robotic surgery than for open surgery and similar for robotic surgery and laparoscopic surgery.¹⁷ Park and colleagues summarized the outcomes of 26 studies involving 1,062 patients who had a radical hysterectomy for stage IA to IIB cervical cancer and found that the incidence of intra- and postoperative complications was similar in patients who had robotic, laparoscopic, or open surgery.¹⁶

Clinical Implications

The driver of minimally invasive surgery for early cervical cancer was a presumed lower incidence of postoperative adverse events and quicker recovery compared to open surgery. Hence, these findings add valuable knowledge to the literature. However, in the past the incidence of adverse events after minimally invasive versus open radical hysterectomy for early cervical cancer has been compared only retrospectively.

Overall, the previously published literature agrees with the findings of the LACC trial regarding the lower estimated blood loss, shorter length of hospital stay, and longer operative time for minimally invasive surgery compared to open surgery. All the studies also agree regarding the conclusion that the incidence of intraoperative complications is similar for minimally invasive and open surgery. However, whereas the LACC study found that the incidence of postoperative adverse events was similar for minimally invasive and open surgery, four of the seven previously published meta-analyses concluded that the incidence of postoperative complications was higher for open surgery.^5,6,14,17

The length of stay in the LACC trial was longer than what would be expected in the United States of America. However, The LACC trial enrolled patients from multiple countries and the median length of stay differed from 3 days to 15 days in various countries, irrespective of health outcomes.

The incidence of adverse events was generally higher in the LACC trial than in previously reported studies. Specifically, the incidence of intraoperative complications was 11% in the LACC trial versus 5.1% to 7.1% in the above-described meta-analyses,^{5–8,14–17} and the incidence of early postoperative adverse events was 42% in the LACC trial versus 10.1% to 25.4% in the meta-analyses.^{5–8,14–17} Most likely, in retrospective series only selected adverse events are recorded, including those that are more obvious, require admission to the hospital, or involve a return to the operating room. By contrast, in the LACC trial, all adverse events were captured and reported, regardless of causality, and this likely resulted in the higher complication rates.

The overall incidence of postoperative adverse events in the LAP2 trial¹⁸ was 17%, compared to 42% in the LACC trial. However, In the LAP2 trial, the incidence of adverse events is based on capture of adverse events only at 6 weeks postoperatively. In the LACC trial, adverse events were collected at four time points (1 week, 6 weeks, Month 3 and Month 6). Therefore, there were more opportunities for patients to report adverse events. If in the LACC trial the reporting of the incidence of adverse events would be limited to 6 weeks as in LAP2, the total number of patients reporting an adverse event would be 100 (18%), which would be strikingly similar to the incidence of postoperative adverse events in LAP2.

Research Implications

These findings will be useful for the planning and design of subsequent studies on the safety and effectiveness of surgical procedures for early cervical cancer. Future clinical trials on this topic should consider monitoring the incidence of adverse events closely.

Strengths and Limitations

The results presented here are likely to be representative of results of radical hysterectomy across the globe because the trial included 33 sites from 14 countries. A strict surgeon accreditation process and proof of proficiency requirements are further strengths of the LACC trial. The LACC trial standardized the assessment of adverse events, had rules for patient selection, timing and type of assessments, and use of common outcome definitions and the LACC trial included standard quality-control procedures for clinical trials. Thus, we believe that the LACC trial results offer greater insight into procedure-specific adverse events than do the previously published studies.

A weakness is that the LACC trial was not powered to detect differences between laparoscopic and robotic surgery. Also, the fact that all adverse events were documented, rather than only clinically relevant adverse events, resulted in high rates of adverse events, some of which may lack clinical relevance.

Conclusions

In conclusion, in the prospective LACC trial, we found that the overall incidences of intraoperative and postoperative adverse events did not differ between minimally invasive and open radical hysterectomy for early cervical cancer.

AJOG at a Glance.

A. Why was the study conducted?

The wide adoption of minimally invasive radical hysterectomy for early cervical cancer was driven by the presumed lower incidence of procedure-related adverse events compared to open radical hysterectomy. However, the existing evidence on the incidence of adverse events following minimally invasive versus open radical hysterectomy for early cervical cancer was either non-randomized or retrospective.

B. What are the key findings?

In this randomized clinical trial that enrolled 631 patients, there was no difference in the overall incidence of intraoperative or postoperative adverse events between minimally invasive and open radical hysterectomy for early cervical cancer.

C. What does this study add to what is already known?

Minimally invasive radical hysterectomy is not associated with lower overall intraoperative or postoperative complication rates compared to the open approach.