
==== Front
J Gynecol Oncol
J Gynecol Oncol
JGO
Journal of Gynecologic Oncology
2005-0380
2005-0399
Asian Society of Gynecologic Oncology; Korean Society of Gynecologic Oncology; Japan Society of Gynecologic Oncology

38425140
10.3802/jgo.2024.35.e60
Original Article
Cervix
Comparison of outcomes of laparotomic and minimally invasive radical hysterectomy in women with early-stage cervical cancer
https://orcid.org/0000-0002-3017-7021
Chang Shu-Han 12*
https://orcid.org/0000-0001-8481-8077
Huang Kuan-Gen 123*
https://orcid.org/0000-0002-6305-540X
Yang Lan-Yan 4
https://orcid.org/0000-0002-2004-1526
Pan Yu-Bin 5
https://orcid.org/0000-0002-9977-9645
Lai Chyong-Huey 123
https://orcid.org/0000-0002-7049-3280
Chou Hung-Hsueh 126
1 Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Branch and Chang Gung University, Taoyuan, Taiwan.
2 Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.
3 College of Medicine, Chang Gung University, Taoyuan, Taiwan.
4 Division of Clinical Trial, Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
5 Clinical Trial Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
6 School of Medicine, National Tsing Hua University, Hsinchu, Taiwan.
Correspondence to Hung-Hsueh Chou. Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Branch and Chang Gung University, 5 Fu-Shin Street, Kueishan, Taoyuan 333, Taiwan. ma2012@cgmh.org.tw
*Shu-Han Chang and Kuan-Gen Huang contribute equally to this study.

9 2024
23 2 2024
35 5 e6022 8 2023
03 1 2024
11 2 2024
© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology
2024
Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Objective

This study compared the outcomes of laparotomic radical hysterectomy (LRH) and minimally invasive radical hysterectomy (MISRH) in patients with early-stage cervical cancer.

Methods

The clinical data of patients with early-stage cervical cancer who underwent LRH or MISRH (laparoscopic/robotic) at Chang Gung Memorial Hospital, Linkou Branch, from 2002 to 2017 were retrospectively reviewed. The surgical safety (operation time, blood loss, blood transfusion rate, length of postoperative stay, and perioperative complications), overall survival (OS), disease-free survival (DFS), and recurrence pattern were analyzed. Propensity score matching (PSM) at a 3:1 ratio was performed to balance prognostic variables.

Results

Of the 760 patients (entire cohort), 614 underwent LRH and 146 underwent MISRH. After PSM, 394 and 140 patients were included in the LRH and MISRH groups, respectively. The 5-year OS rate was significantly lower in the MISRH group than in the LRH group (85.6% vs. 93.2%, p=0.043), and the 5-year DFS rate (p=0.21) did not differ significantly. After PSM, the 5-year OS rates did not differ significantly between the MISRH and LRH groups (87.1% vs. 92.1%, p=0.393). The MISRH group had a significantly shorter operation time (p<0.001), lower intraoperative blood loss (p<0.001), lower blood transfusion rate (p<0.001), and shorter postoperative stay (p<0.001) but a significantly higher rate of intraoperative bladder injury (p<0.001) than the LRH group.

Conclusion

After PSM, MISRH is associated with nonsignificantly lower OS but a significantly higher risk of intraoperative urological complications than LRH.

Synopsis

In patients with early-stage cervical cancer, overall survival rate was significantly worse in minimally invasive radical hysterectomy (MISRH) group than laparotomic group. After propensity score matching, the difference was not significant. MISRH group is associated with a significantly higher rate of intra-operative bladder injury.

Graphical Abstract

Cervical Cancer
Hysterectomy
Laparoscopy
Laparotomy
Minimally Invasive Surgical Procedures
Chang Gung Medical Foundation https://doi.org/10.13039/501100004606 CORPG3J0421 CMRPG3K1501-2 National Science and Technology Council https://doi.org/10.13039/501100020950 NMRPG3J0551 Ministry of Health and Welfare https://doi.org/10.13039/100008903 MOHW112-TDU-B-212-144005
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pmcINTRODUCTION

Cervical cancer is the third most common cancer and the fourth leading cause of death among women worldwide [1]. Radical hysterectomy (RH) with pelvic lymphadenectomy remains the standard surgical treatment for early-stage cervical cancer, with a high 5-year survival rate.

Traditionally, RH was performed using laparotomy; however, this approach is associated with high rates of perioperative and long-term complications [234]. With advancements in surgical techniques over the past 2 decades, minimally invasive surgery (MIS) has become the preferred method for gynecological operations, including RH for early-stage cervical cancer [5]. Minimally invasive RH (MISRH) can be performed using a laparoscopic or robotic approach. A series of studies have shown that MISRH is associated with fewer perioperative complications than laparotomic RH (LRH), including lower operative pain, lower blood loss, lower rate of blood transfusion, shorter hospital stay, shorter duration of bladder catheterization, quicker return to normal bowel activity, and faster recovery [67891011121314151617].

However, in 2018, the Laparoscopic Approach to Cervical Cancer (LACC) trial [18], a phase III prospective, multicenter, randomized controlled trial (RCT), provided unexpected results. Compared with open surgery, MISRH was associated with significantly lower disease-free survival (DFS) and overall survival (OS) at 3 years postoperatively. Several retrospective studies comparing the outcomes of MISRH and LRH were also published after the LACC trial. For instance, a study involving 2,461 patients with stage IA2 or IB1 cervical cancer from the National Cancer Database revealed a higher mortality rate in the MISRH group than in the LRH group (9.1% vs. 5.3%, p=0.002) [19]. Chen et al. [20] reported a significantly worse 5-year DFS rate for stage IB1 cervical cancer patients with tumor sizes ≤2 cm in the MISRH group (MISRH group, 90.4% vs. LRH group, 97.7%; p=0.02). Moreover, Margul et al. [21] found that in women with ≥2 cm, stage IB1 cervical tumors, MISRH was associated with a significantly lower 5-year OS rate than LRH (MISRH, 81.3% vs. LRH, 90.8%; p<0.001). However, a recent multicenter retrospective study in the United States revealed that the 3-year OS rates were not significantly different between the MISRH and LRH groups (95.8% vs. 96.0%, p=0.8) [22].

This study compared the outcomes of patients with early-stage cervical cancer who underwent MISRH and LRH at a tertiary institutional hospital in Taiwan.

MATERIALS AND METHODS

1. Patients and study design

This retrospective study recruited patients with early-stage cervical cancer who underwent RH through laparotomy, laparoscopy, or robotic surgery at Chang Gung Memorial Hospital (CGMH), Linkou Branch, from 2002 to 2017. The study protocol was reviewed and approved by the Institutional Review Board of CGMH (IRB201800803B0), and the study was conducted in accordance with the Declaration of Helsinki. Patients who underwent laparoscopic RH and robotic RH were included in the MISRH group, and the outcomes of patients in the MISRH and LRH groups were compared. The primary endpoints were the OS and DFS rates. The secondary endpoints were the safety of surgery, including operation time, estimated blood loss, blood transfusion rate (from the intraoperative period till postoperative day 7), length of postoperative stay, perioperative complications, and recurrence rate.

Postoperative radiotherapy/chemoradiotherapy was recommended for high-risk patients: positive pelvic nodes, positive surgical margin or full thickness cervical stromal invasion, or positive parametrium [23]. Patients were identified from the Taiwan Cancer Registry Center, CGMH, and their clinical data were obtained from electronic medical records and medical charts. The survival status of the patients was confirmed using the Taiwan Human Mortality Database.

Patients were eligible if they had histologically proven cervical cancer of stage IB–IIA according to the staging system of the International Federation of Gynecology and Obstetrics (2018) and had undergone type II or III RH (Piver classification). The exclusion criteria were a history of abdominal or pelvic radiotherapy before the operation, prior diagnosis of other malignancies within 5 years, or recurrence. Patients in the 2 groups were matched through propensity score matching (PSM) to reduce bias in the outcome estimates [24]. To reduce the impact of censoring data on survival estimates, the outcomes of patients lost to follow-up were obtained from the Taiwan Human Mortality Database and Taiwan Cancer Registry Center.

2. Statistical analysis

Descriptive statistics were used to summarize cohort characteristics; mean and standard deviation values are reported for continuous variables, and frequencies and percentages are reported for categorical variables. For between-group comparisons, continuous variables were compared using an independent t-test, whereas categorical variables were compared using the Pearson χ2 test or Fisher’s exact test, as appropriate. The Kaplan-Meier method was used to construct the OS and DFS curves, and the differences between groups were compared using a log-rank test. Cox regression analysis was performed to identify the independent predictors of OS and DFS. PSM was performed to compare the effects of LRH and MISRH. The LRH and MISRH groups were matched at a 3:1 ratio by using multiple logistic regression. Six matching variables (age, grade, depth of stromal invasion, pelvic lymph node (LN), parametrial invasion, and stage) were used to balance the potential confounding factors in baseline characteristics. Power analysis was performed to evaluate the type II error resulting from the limitation of the sample size. All analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA). Statistical significance was set at a 2-tailed p-value of <0.05.

RESULTS

This study included a total of 760 patients (entire cohort). Of these, 614 patients (80.8%) underwent LRH, and 146 (19.2%) underwent MISRH. In the MISRH group, 139 patients underwent laparoscopic RH, and 7 underwent robotic RH. The median follow-up time was 164.2 months in the LRH group and 131.4 months in the MISRH group. The baseline clinical and pathological characteristics are presented in Table 1. Age (p=0.009), parametrial extension (13% vs. 4.1%, p<0.001), and adenocarcinoma distribution (64.4% vs. 54.4%, p=0.029) significantly differed between the MISRH and LRH groups. After PSM, no differences were noted in the 6 matching variables. The distributions of propensity scores between the groups before and after matching are shown in Fig. S1. Compared with the LRH group, the MISRH group had a shorter mean operation time (339.2±83 vs. 281.6±72.2 minutes, p<0.001), lower blood loss (928±707.4 vs. 359.9±329.5 mL, p<0.001), and shorter length of postoperative hospital stay (9.2±3.7 vs. 7.9±3.4 days, p<0.001). The differences in these surgical variables remained significant after PSM.

Table 1 Baseline clinical and pathological characteristics

Characteristics	Entire cohort	Propensity score matching (3:1)	
LRH (n=614)	MISRH (n=146)	p-value	LRH (n=394)	MISRH (n=140)	p-value	
Age (yr)	48.3±9.9	50.7±10.8	0.009	49.4±10.3	50.3±10.6	0.393	
Tumor size (cm)			0.402			0.108	
	<2	267 (43.7)	68 (47.9)	186 (47.4)	65 (47.8)	
	2–4	257 (42.1)	51 (35.9)	167 (42.6)	49 (36)	
	>4	87 (14.2)	23 (16.2)	39 (9.9)	22 (16.2)	
Grade			0.051			0.847	
	Well	107 (17.4)	14 (9.6)	37 (9.4)	14 (10)	
	Moderately	206 (33.6)	63 (43.2)	167 (42.4)	58 (41.4)	
	Poorly/Undifferentiated	240 (39.1)	56 (38.4)	147 (37.3)	56 (40)	
	Unknown	61 (9.9)	13 (8.9)	43 (10.9)	12 (8.6)	
Deep stromal invasion			0.099			0.146	
	No	379 (61.9)	79 (54.5)	247 (62.7)	78 (55.7)	
	Yes	233 (38.1)	66 (45.5)	147 (37.3)	62 (44.3)	
Pelvic LN metastasis			0.748			0.716	
	No	550 (89.9)	129 (89)	356 (90.4)	125 (89.3)	
	Yes	62 (10.1)	16 (11)	38 (9.6)	15 (10.7)	
Parametrial invasion			<0.001			0.055	
	No	589 (95.9)	127 (87)	373 (94.7)	126 (90)	
	Yes	25 (4.1)	19 (13)	21 (5.3)	14 (10)	
Stage			0.165			0.67	
	IB1	500 (81.4)	126 (86.3)	346 (87.8)	121 (86.4)	
	>IB1	114 (18.6)	20 (13.7)	48 (12.2)	19 (13.6)	
Histology			0.029			0.364	
	Non-SCC	280 (45.6)	52 (35.6)	155 (39.3)	49 (35)	
	SCC	334 (54.4)	94 (64.4)	239 (60.7)	91 (65)	
Adjuvant radiation			0.406			0.504	
	No	458 (74.6)	104 (71.2)	301 (76.4)	103 (73.6)	
	Yes	156 (25.4)	42 (28.8)	93 (23.6)	37 (26.4)	
Surgical variables							
Operation time (min)	339.2±83.0	281.6±72.2	<0.001	337.6±84.3	279.8±70.0	<0.001	
Blood loss	928.0±707.4	359.9±329.5	<0.001	909.1±669.2	362.9±332.3	<0.001	
Postoperative stay (days)	9.2±3.7	7.9±3.4	<0.001	9.2±3.8	7.9±3.3	<0.001	
Values are presented as mean ± standard deviation or count (%).

LN, lymph node; LRH, laparotomic radical hysterectomy; MISRH, minimal invasive radical hysterectomy; SCC, squamous cell carcinoma.

Table 2 provides a summary of the surgery-related complications based on the Clavien-Dindo classification. The percentage of patients with intraoperative blood loss >1,500 mL was significantly higher in the LRH group than in the MISRH group (p<0.001). By contrast, the MISRH group had a higher incidence of bladder injury (8.2% vs. 0.3%, p<0.001) and ureteral injury (2.7% vs. 0.5%, p=0.029). After PSM, the percentage of patients with intraoperative blood loss >1,500 mL remained significantly higher in the LRH group than in the MISRH group (p<0.001). Moreover, the MISRH group had a significantly higher incidence of bladder injury (p<0.001) and a nonsignificantly higher incidence of ureteral injury (p=0.081) than the LRH group. No statistically significant difference was noted between the 2 groups in terms of colonic injury, obturator nerve or main vessel injury, wound infection/dehiscence, and leg thrombosis before and after PSM. The blood transfusion rate was significantly higher in the LRH group than in the MISRH group (PSM: 56.5% vs. 19.9%, p<0.001, and after PSM: 55.1% vs. 20%, p<0.001, respectively).

Table 2 Surgery related complications

Clavien-Dindo classification	Characteristics	Entire cohort	Propensity score matching (3:1)	
LRH (n=614)	MISRH (n=146)	p-value	LRH (n=394)	MISRH (n=140)	p-value	
Intraoperative complications								
	Grade I	Bladder injury, bladder perforation*	0 (0)	1 (0.7)	0.192	0 (0)	1 (0.7)	0.262	
	Grade II	Blood loss >1,500 mL	90 (14.7)	1 (0.7)	<0.001	56 (14.2)	1 (0.7)	<0.001	
	Grade III	Colon injury	0 (0)	1 (0.7)	0.192	0 (0)	0 (0)	-	
Bladder injury, bladder perforation	2 (0.3)	11 (7.5)	<0.001	1 (0.3)	9 (6.4)	<0.001	
Ureter injury	3 (0.5)	4 (2.7)	0.028	3 (0.8)	4 (2.9)	0.081	
Obturator nerve injury	0 (0)	1 (0.7)	0.192	0 (0)	1 (0.7)	0.262	
Main vessel injury	1 (0.2)	1 (0.7)	0.348	0 (0)	1 (0.7)	0.262	
Postoperative complications								
	Grade II	Thrombosis	1 (0.2)	0 (0)	1.000	1 (0.3)	0 (0)	1.000	
	Grade III	Wound infection, immediate (<2 wk)	1 (0.2)	0 (0)	1.000	1 (0.3)	0 (0)	1.000	
Wound dehiscence >2 wk	2 (0.3)	0 (0)	1.000	2 (0.5)	0 (0)	1.000	
Values are presented as count (%).

LRH, laparotomic radical hysterectomy; MISRH, minimal invasive radical hysterectomy.

*One patient with bladder injury was found to have only mild thermal injury under post-operative cystoscopy, without the need for pharmacological or surgical interventions.

The recurrence rates and failure patterns are shown in Table 3. The distant failure rate was higher in the MISRH cohort than in the LRH cohort, although the result was nonsignificant (11% vs. 6.8%, p=0.092). However, this difference was not evident (p=0.324) after PSM.

Table 3 Failure patterns

Characteristics	Entire cohort	Propensity score matching (3:1)	
LRH (n=614)	MISRH (n=146)	p-value	LRH (n=394)	MISRH (n=140)	p-value	
Recurrence	69 (11.2)	21 (14.4)	0.290	47 (11.9)	19 (13.6)	0.612	
Recurrent site							
	Local	20 (3.3)	6 (4.1)	0.613	14 (3.6)	6 (4.3)	0.695	
	Regional	17 (2.8)	4 (2.7)	1.000	13 (3.3)	4 (2.9)	1.000	
	Distant	42 (6.8)	16 (11)	0.092	29 (7.4)	14 (10)	0.324	
Values are presented as count (%).

LRH, laparotomic radical hysterectomy; MISRH, minimal invasive radical hysterectomy.

In multivariate Cox regression analyses for OS, age (hazard ratio [HR]=1.031, 95% confidence interval [CI]=1.009–1.057, p=0.004), pelvic LN metastasis (HR=2.174, 95% CI=1.246–3.973, p=0.006), parametrial invasion (HR=1.936, 95% CI=1.026–3.654, p=0.041), and tumor histology (squamous cell carcinoma [SCC] vs. non-SCC: HR=0.624, 95% CI=0.400–0.974, p=0.038) were found to be significant predictors. After PSM, age and tumor histology remained significant predictors, whereas pelvic LN metastasis, parametrial invasion, and length of postoperative stay became nonsignificant (Table 4). For DFS, cervical stromal invasion and tumor histology were significant predictors (HR=2.293, 95% CI=1.105–4.757, p=0.026 and HR=0.445, 95% CI=0.247–0.802, p=0.007, respectively) (Table S1). Stromal invasion was associated with poor outcomes, whereas SCC was associated with more favorable outcomes. PSM was performed for age, pelvic LN metastasis, parametrial invasion, and tumor histology. After PSM, 394 and 140 patients were included in the LRH and MISRH groups, respectively, in which these significant variables were well balanced (Table 1).

Table 4 Multivariate analysis of prognostic variables in the cohort for overall survival

Variables	Entire cohort	Propensity score matching (3:1)	
HR (95% CI)	p-value	HR (95% CI)	p-value	
Age (yr)	1.031 (1.01–1.053)	0.004	1.033 (1.009–1.057)	0.007	
Tumor size (cm)					
	<2	1.000 (ref)		1.000 (ref)		
	2–4	1.305 (0.790–2.155)	0.299	1.269 (0.717–2.244)	0.413	
	>4	1.308 (0.627–2.732)	0.474	1.334 (0.579–3.073)	0.499	
Grade					
	Well	1.000 (ref)		1.000 (ref)		
	Moderately	0.982 (0.554–1.739)	0.949	0.719 (0.351–1.474)	0.367	
	Poorly/Undifferentiated	0.547 (0.295–1.014)	0.055	0.402 (0.188–0.862)	0.019	
	Unknown	1.078 (0.477–2.437)	0.856	0.618 (0.227–1.680)	0.345	
Deep stromal invasion		0.500		0.638	
	No	1.000 (ref)	1.000 (ref)	
	Yes	1.201 (0.705–2.047)	1.162 (0.622–2.169)	
Pelvic LN metastasis		0.006		0.069	
	No	1.000 (ref)	1.000 (ref)	
	Yes	2.174 (1.246–3.793)	1.892 (0.952–3.758)	
Parametrial invasion		0.041		0.194	
	No	1.000 (ref)	1.000 (ref)	
	Yes	1.936 (1.026–3.654)	1.662 (0.773–3.577)	
Stage		0.962		0.925	
	IB1	1.000 (ref)	1.000 (ref)	
	>IB1	1.015 (0.560–1.838)	1.035 (0.504–2.126)	
Histology		0.038		0.046	
	Non-SCC	1.000 (ref)	1.000 (ref)	
	SCC	0.624 (0.400–0.974)	0.594 (0.356–0.992)	
Adjuvant radiation		0.397		0.548	
	No	1.000 (ref)	1.000 (ref)	
	Yes	1.298 (0.710–2.374)	1.250 (0.604–2.588)	
Operation time (min)	1.001 (0.999–1.004)	0.375	1.002 (0.999–1.005)	0.125	
Blood loss	1.000 (0.999–1.000)	0.126	1.000 (1.000–1.000)	0.857	
Postoperative stay (days)	1.049 (1.008–1.090)	0.018	1.031 (0.982–1.084)	0.221	
CI, confidence interval; HR, hazard ratio; LN, lymph node; SCC, squamous cell carcinoma.

The OS and DFS curves of the entire cohort are shown in Fig. 1. The 5-year OS rate was significantly lower in the MISRH group than in the LRH group (85.6% vs. 93.2%, p=0.043). The 5-year DFS rate was 86.0% in the MISRH group and 90.0% in the LRH group (p=0.21). After PSM, the 5-year OS rate was lower in the MISRH group than in the LRH group, although nonsignificant (87.1% vs. 92.1%, p=0.393) (Fig. 2). After PSM, the 5-year OS rates of the MISRH and LRH groups and of the subgroups of patients with tumor sizes <2 cm (93.8% vs. 95.7%, p=0.948), 2–4 cm (83.7% vs. 89.2%, p=0.568), and >4 cm (77.3% vs. 87.2%, p=0.484) are presented in Fig. S2.

Fig. 1 OS (A) and DFS (B) rates between the 2 surgical methods in the entire cohort.

DFS, disease-free survival; LRH, laparotomic radical hysterectomy; MISRH, minimally invasive radical hysterectomy; OP, operation; OS, overall survival.

Fig. 2 OS (A) and DFS (B) rates between the 2 surgical methods in the propensity score–matched cohort.

DFS, disease-free survival; LRH, laparotomic radical hysterectomy; MISRH, minimally invasive radical hysterectomy; OP, operation; OS, overall survival.

After PSM, no significant difference was noted in the 5-year DFS rates between the MISRH and LRH groups (86.9% vs. 89.1%, p=0.529) (Fig. 2B) and in the subgroups of patients with tumor sizes <2 cm (95.2% vs. 95.2%, p=0.842), 2–4 cm (87.5% vs. 85.5%, p=0.836), and >4 cm (63.6% vs. 74.3%, p=0.286) (Fig. S3). Given the limitation of the sample size in each subgroup after PSM, the power achieved was only 28% for patients with tumor sizes >4 cm and only 55% for the whole propensity score–matched cohort.

DISCUSSION

Despite the availability of human papillomavirus vaccination and screening strategies, cervical cancer remains the fourth most common cancer in women globally, with approximately 604,000 new cases and 342,000 deaths being reported in 2020 according to the statistics of the World Health Organization. With an increasing number of patients with early-stage cervical cancer undergoing MISRH in the past 2 decades, the survival outcomes of MISRH compared with LRH has attracted increasing research attention.

Previous studies comparing the outcomes of different surgical methods have reported varying results. Several meta-analyses have proven that MISRH is safe and results in fewer perioperative complications and faster recovery than open surgery [82324252627]. The SUCCOR study, an international European cohort observational study, concluded that MISRH increased the risks of relapse and death in patients with cervical cancer compared with open surgery [28]. Moreover, in a retrospective cohort study, Cusimano et al. [29] demonstrated that MISRH was associated with increased rates of death and recurrence in patients with stage IB cervical cancer. In a meta-analysis, Wang et al. [30] showed that MISRH was associated with poorer survival outcomes than open surgery. In a retrospective study, Chen et al. [31] reported that traditional LRH had a lower recurrence rate than laparoscopic surgery in patients with tumor size <2 cm.

This retrospective study compared the long-term survival outcomes of patients with early-stage cervical cancer who underwent MISRH and those who underwent LRH. Before PSM, the 5-year OS rate in the MISRH group was lower than that in the LRH group (p=0.043). After PSM, although the 5-year OS rate was lower and the 5-year DFS rate was approximately 10% lower in patients who underwent MISRH and had tumor size >4 cm, no significant difference was noted in the 5-year OS and 5-year DFS rates between the MISRH and LRH groups and between subgroups of patients with tumor sizes <2 cm, 2–4 cm, and >4 cm. Similar results have been reported in other studies [827]. Nam et al. [32] compared 263 pairs of patients with early-stage cervical cancer who underwent MISRH and LRH and found no difference in survival outcomes between the 2 groups. Moreover, in a matched cohort study, Wang et al. [7] compared 203 pairs of patients who underwent MISRH and LRH, and the results revealed similar 5-year DFS and OS rates in the 2 groups.

Similar to previous findings [333435], in this study, we found that the recurrence rates did not differ significantly between the MISRH and LRH groups. However, a slight nonsignificant increase was noted in the MISRH group for both local and distant sites, which may be attributed to the following reasons: First, the use of a uterine manipulator in MIS may increase the risk of tumor spillage. Second, the use of insufflation gas (carbon dioxide) may cause the abdominal metastasis of tumor cells, as mentioned in other studies [3637]. Kong et al. [38] compared disease recurrence rates and noted a higher recurrence rate in the intracorporeal colpotomy group than in the vaginal colpotomy group (16% vs. 5%). The robotic-assisted approach to cervical cancer trial (NCT03719547), an open-label RCT launched in 2019 that aims to enroll 768 subjects [39], will provide valuable evidence for the surgical management of early-stage cervical cancer.

Our study revealed a shorter operation time, lower blood loss, lower blood transfusion rate, and shorter postoperative hospital stay in the MISRH group; these results are similar to those of other studies [678910111213141516]. The proportion with bladder injury was higher in the MISRH group (7.1% vs. 0.3%, p<0.001) before and after PSM. Moreover, the incidence of ureteral injury was higher in the MISRH group; however, it did not reach statistical significance (2.9% vs. 0.8%, p=0.082) after PSM. The bladder injury rate was significantly higher in the MISRH group than in the LRH group in our study (p<0.001). Similarly, in a meta-analysis of urological complications, the odds ratio was significantly higher (1.97, 95% CI=1.23–3.13) in the MISRH group than in the LRH group [40].

The strength of this study includes that first, we performed PSM at a 3:1 ratio (LRH:MISRH) to correct the imbalance of characteristics of the 2 groups. Second, a large case number was included and analyzed in a single medical center with well-trained and experienced surgeons. Besides, our results were consistent with those studies previously published. Our retrospective study has some limitations. First, some data were too old to be retrieved from either electronic records or medical charts. Second, the sample size of patients with tumor size >4 cm was relatively small in the MISRH group (n=22, 16.2%) and LRH group (n=39, 9.9%). Finally, power analysis showed only 55% power in the whole propensity score–matched cohort (type II error=0.45).

In our study on patients with early-stage cervical cancer, MISRH was associated with shorter operation time, lower intraoperative blood loss, lower blood transfusion rate, and shorter postoperative hospital stay but a higher rate of intraoperative bladder injury/perforation than LRH. After PSM, MISRH is associated with non-significantly lower OS, similar 5-year DFS and recurrence rates.

ACKNOWLEDGEMENTS

The authors thank all the members of the Cancer Center, Chang Gung Memorial Hospital, for their invaluable help.

SUPPLEMENTARY MATERIALS

Table S1

Multivariate analysis of prognostic variables in the cohort for disease-free survival

Fig. S1

Propensity score distribution before and after matching.

Fig. S2

OS among surgical method in tumor size <2 cm (A), 2–4 cm (B), and >4 cm (C) in propensity score matching cohort.

Fig. S3

DFS among surgical method in tumor size <2 cm (A), 2–4 cm (B), and >4 cm (C) in propensity score matching cohort.

Funding: This study was supported by grants from the Chang Gung Medical Foundation, Taiwan (CORPG3J0421 and CMRPG3K1501-2), National Science and Technology Council (NMRPG3J0551), and Ministry of Health and Welfare, Taiwan (MOHW112-TDU-B-212-144005).

Conflict of Interest: No potential conflict of interest relevant to this article was reported.

Author Contributions: Conceptualization: C.S.H., H.K.G., C.H.H.

Data curation: C.S.H., H.K.G., L.C.H., C.H.H.

Formal analysis: Y.L.Y., P.Y.B.

Writing - original draft: C.S.H., H.K.G., Y.L.Y., P.Y.B., L.C.H., C.H.H.

Writing - review & editing: C.S.H., H.K.G., Y.L.Y., P.Y.B., L.C.H., C.H.H.
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