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\begin{document}

\title{Laparoscopic versus open radical hysterectomy in early-stage cervical
adenocarcinoma in FIGO2018: long-term survival outcomes after propensity
score matching}



\author[1]{Chunlin Chen}%
\author[1]{Ping Liu}%
\author[1]{Zhaohong Yin}%
\author[1]{Zhumei Cui}%
\author[2]{Shan Kang}%
\author[3]{Mei Ji}%
\author[4]{donglin Li}%
\author[1]{Biliang Chen}%
\author[1]{Xuemei Zhan}%
\author[1]{Yi Zhang}%
\author[1]{Weidong Zhao}%
\author[1]{Weili Li}%
\affil[1]{Affiliation not available}%
\affil[2]{Fourth Hospital，Hebei Medical University}%
\affil[3]{The First Affiliated Hospital of Zhengzhou University}%
\affil[4]{Guizhou Provincial People`s Hospital}%


\vspace{-1em}



  
  \date{May 18, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Objective To compare long-term survival outcomes between laparoscopic
radical hysterectomy (LRH) and open radical hysterectomy (ORH) in
early-stage cervical adenocarcinoma under the new FIGO 2018 staging
guideline. Design Retrospective study Setting and population Early-stage
cervical adenocarcinoma received LRH and ORH; 47 Chinese hospitals.
Methods We matched patients with early-stage cervical adenocarcinoma in
the new FIGO 2018 staging guideline with known risk factors for
recurrence who underwent ORH and LRH. Main Outcome Measures 5-year
overall survival and 5-year disease-free survival rates Results In
total, 549 patients were enrolled in our study, including 235 patients
in LRH group and 314 in ORH group. After matching some factors that may
affect the prognosis, each group had 223 patients. There was no
difference in DFS between LRH and ORH in risk-adjusted analysis
(HR1.258, 95\% CI: 0.507-3.125, P=0.621). There was no difference in OS
between LRH and ORH in risk-adjusted analysis (HR1.961, 95\% CI:
0.536-7.183, P=0.309). LRH resulted in significantly lower estimated
blood loss (361.2 versus 165.3 ml, P \textless{} 0.001) and shorter
postoperative anal exhaust time (2.8 versus 2.5 days, P = 0.003) .
Intraoperative complication ( 2.7\% versus 5.8\%,P=0.101) and
postoperative complication ( 5.8\% versus 6.3\%, P=0.843) rates were
similar in the two groups. Conclusions LRH has comparable survival
outcomes with ORH and was associated with earlier recovery in
early-stage adenocarcinoma of the uterine cervix. LRH may be an
appropriate option for early-stage cervical adenocarcinoma compared with
ORH.%
\end{abstract}%



\sloppy


\textbf{Laparoscopic versus open radical hysterectomy in early-stage
cervical adenocarcinoma in FIGO2018: long-term survival outcomes after
propensity score matching}

Zhaohong Yin,MA \textsuperscript{a,1}\textbf{,}Zhumei Cui, PhD
\textsuperscript{b,1}, Shan Kang, PhD \textsuperscript{c,1}, Mei Ji,
PhD\textsuperscript{d}, Li Donglin, PhD\textsuperscript{e} , Biliang
Chen, PhD\textsuperscript{f}, Xuemei Zhan, PhD\textsuperscript{g}, Yi
Zhang, PhD\textsuperscript{h}, Weidong Zhao, PhD\textsuperscript{i},
Weili Li, PhD\textsuperscript{a}, Chunlin Chen, PhD
\textsuperscript{a,}*, Ping Liu, PhD\textsuperscript{a,}*

Zhaohong Yin,MA \textsuperscript{a,1}\textbf{,} Zhumei Cui,
PhD\textsuperscript{b,1}, and Shan Kang, PhD \textsuperscript{c,1} are
contributed equally to this work.

a Department of Obstetrics and Gynecology, Nanfang Hospital, Southern
Medical University, No.1838, North Guanghzou Avenue, Guangzhou, 510515,
China

b Department of Obstetrics and Gynecology, The Affiliated Hospital of
Qingdao University, Qingdao, 266000, China

c Department of Gynecology, The Forth Hospital of Hebei Medical
University, Shijiazhuang, 050000, China

d Department of Obstetrics and Gynecology, The First Affiliated Hospital
of Zhengzhou University, Zhengzhou, 450000,China

e Department of Obstetrics and Gynecology, Guizhou people's Hospital,
Guiyang, 550000, China

f Department of Obstetrics and Gynecology, Xijing Hospital of Airforce
Medical University, Xi'an, 710000, China

g Department of Obstetrics and Gynecology, Affiliated Jiangmen Hospital
of SUN YAT-SEN University, Jiangmen, 529000, China.

h Department of Gynecology, The First Hospital of China Medical
University, Shenyang, 110000, China

i Department of Gynecology and Oncology, Anhui Provincial Cancer
Hospital, Hefei, Anhui 230009, P.R. China

* \textbf{Corresponding author :}

Chunlin Chen:Department of Obstetrics and Gynecology, Nan fang

Hospital,Southern Medical University, No. 1838, Guangzhou Avenue,
Guangzhou, 510515, China. Tel: 8620-62787562,E-mail address:
ccl1@smu.edu.cn.

Ping Liu: Department of Obstetrics and Gynecology, Nan fang

Hospital,Southern Medical University, No. 1838, Guangzhou Avenue,
Guangzhou, 510515, China. Tel: 8620-62787562,E-mail address:
lpivy@126.com

\textbf{ABSTRACT}

\textbf{Background} To compare long-term survival outcomes between
laparoscopic radical hysterectomy (LRH) and open radical hysterectomy
(ORH) in early-stage cervical adenocarcinoma under the new FIGO 2018
staging guideline.

\textbf{Methods} Based on the clinical diagnosis and treatment for
cervical cancer in mainland China (Four C) database, we matched patients
with early-stage cervical adenocarcinoma in the new FIGO 2018 staging
guideline with known risk factors for recurrence who underwent ORH and
LRH.

\textbf{Results} In total, 549 patients were enrolled in our study,
including 235 patients in LRH group and 314 in ORH group. After matching
some factors that may affect the prognosis, each group had 223 patients.
There was no difference in DFS between LRH and ORH either in unadjusted
analysis (HR1.323, 95\% CI: 0.578-3.029, P=0.508) or in risk-adjusted
analysis (HR1.258, 95\% CI: 0.507-3.125, P=0.621). There was no
difference in OS between LRH and ORH either in the unadjusted analysis
(HR2.624, 95\% CI: 0.784-8.778, P=0.117) or in risk-adjusted analysis
(HR1.961, 95\% CI: 0.536-7.183, P=0.309). LRH resulted in significantly
lower estimated blood loss (unadjusted: 355.0 versus 161.5 ml, P
\textless{} 0.001; adjusted: 361.2 versus 165.3 ml, P \textless{} 0.001)
and shorter postoperative anal exhaust time (unadjusted: 2.8 versus 2.5
days, P = 0.002; adjusted: 2.8 versus 2.5 days, P = 0.003) both in
unadjusted analysis and in risk-adjusted analysis. Intraoperative
complication (unadjusted: 2.5\% versus 5.5\%,P=0.391; adjusted: 2.7\%
versus 5.8\%,P=0.101) and postoperative complication (unadjusted: 6.7\%
versus 6.0\%, P=0.729; adjusted: 5.8\% versus 6.3\%, P=0.843) rates were
similar in the two groups both in unadjusted analysis and in
risk-adjusted analysis.

\textbf{Conclusions} LRH has comparable survival outcomes with ORH and
was associated with earlier recovery in early-stage adenocarcinoma of
the uterine cervix. LRH may be an appropriate option for early-stage
cervical adenocarcinoma compared with ORH.

\textbf{Key words:} early-stage cervical adenocarcinoma, laparoscopic
radical hysterectomy, open radical hysterectomy, survival outcomes,
surgical outcomes

\textbf{Tweetable abstract}

There was no difference in DFS and OS between LRH and ORH.

LRH resulted in significantly lower estimated blood loss and shorter
postoperative anal exhaust time.

Intraoperative complication and postoperative complication rates were
similar in the two groups.

\textbf{Introduction}

Cervical cancer is the most common malignant tumor of female urogenital
tract. The latest global cancer statistics show that there were 569,847
new cases of cervical cancer and 311,365 deaths in
2018\textsuperscript{{[}1{]}}.Cervical cancer incidence and mortality
have decreased thanks to the popularization of cervical cancer
screening\textsuperscript{{[}2{]}}. The distribution of cervical cancer
histological types has changed significantly in countries with
systematic cervical screening. Although cervical squamous carcinoma
remains the most common histological type worldwide, the incidence of
cervical adenocarcinoma has been increasing for
decades\textsuperscript{{[}3-5{]}}.

In previous studies, it is generally believed that the prognosis of
cervical adenocarcinoma is inferior to that of cervical squamous
carcinoma. Most authors believed that adenocarcinoma is more prone to
lymph node, ovarian, and distant metastases than cervical squamous
carcinoma, and therefore has a worse
prognosis\textsuperscript{{[}6-8{]}}. In 2018 revised International
Federation of Gynecology and Obstetrics (FIGO) cervical cancer staging
guideline, lymph node-positive cases in stage IIIB and previous stages
were classified as stage IIIC, and stage IB1 in FIGO 2009 staging
guideline(tumor diameter [?] 4 cm) was changed to stage IB1 (tumor
diameter [?] 2 cm) and IB2 (tumor diameter \textgreater{} 2 cm and [?]4cm)in
FIGO 2018 staging guideline\textsuperscript{{[}9{]}}. Under the new
staging guideline, the surgical treatment of early-stage cervical cancer
follows the original content in the National Comprehensive Cancer
Network (NCCN) guidelines. Quite a few articles about arguments on
laparoscopic surgery and laparotomy surgery for early-stage cervical
cancer had been reported\textsuperscript{{[}10-14{]}},but there is few
reports on the indications of laparoscopic surgery for early stage
cervical adenocarcinoma under the new staging guideline. Our study
screened the cases of early cervical adenocarcinoma in FIGO 2018 staging
guideline from the Four C database, and compared the oncological
outcomes of laparoscopic and laparotomy radical hysterectomy for
early-stage cervical adenocarcinoma.

\textbf{Methods}

\textbf{Data Source}

This multicenter retrospective study was approved by the ethics
committee of the Nanfang Hospital of Southern Medical University (No.
NFEC-2017-135) and was registered with the International Clinical Trials
Registry Platform Search Port (https://apps.who.int/trialsearch/),
clinical trial registration number CHiCTR1800017778. This database,
which was established by the collaboration of 47 Chinese hospitals and
comprises a total of 63,926 cases, includes hospitalized cervical cancer
patients from 2004 to 2018. The 47 hospitals participating in the study
are all located in mainland China and can independently carry out
laparoscopic or open radical hysterectomy. The methods of data
collection, entry, follow-up, double entry and database construction in
this database are the same as the previous articles published by our
team\textsuperscript{{[}15-17{]}}\begin{CJK}{UTF8}{gbsn}。

\end{CJK}\selectlanguage{english}\textbf{Cohort Selection}

The inclusion criteria were as follows: received primary surgical
treatment, aged 18 years or older, met FIGO2018 stage IA1 with LVSI to
IB2 and FIGO2018 stageIIA1, cervical adenocarcinoma, no neoadjuvant
chemotherapy or previous radiation therapy, underwent type B or type C
radical hysterectomy + pelvic lymphadenectomy \selectlanguage{ngerman}± para-abdominal aortic
lymphadenectomy, had total laparoscopic or laparotomy as a surgical
approach, and received standardized postoperative adjuvant therapy. The
exclusion criteria were as follows: patients lost to follow up, patients
with pregnancy, patients found to be cervical cancer incidentally after
hysterectomy, patients with cervical stump carcinoma, patients with
other malignant tumors, and patients who did not meet the inclusion
criteria. The overall flowchart is shown in Figure 1.

\textbf{Outcome observation}

The 5-year overall survival and 5-year disease-free survival rates of
patients received laparoscopy or laparotomy were compared.

\textbf{Postoperative adjuvant therapy}

According to NCCN guidelines and FIGO
guidelines\textsuperscript{{[}18-21{]}}\selectlanguage{english},patients with one of the
high-risk factors (positive lymph nodes, positive vaginal margins, and
parametrial infiltration) were recommended postoperative concurrent
chemoradiotherapy. Patients with intermediate-risk factors, such as
bulky tumors, deep cervical stromal invasion, or lymphovascular invasion
in accordance with Gynecologic Oncology Group 92
criteria\textsuperscript{{[}22{]}} were recommended for adjuvant
radiotherapy, adenocarcinoma is also one of the intermediate risk
factors\textsuperscript{{[}19{]}}.

\textbf{Propensity score matching}

Since there may be differences in clinical data (age, tumor diameter,
and postoperative pathological risk factors) between the ORH and LRH
groups before matching, we used the PSM method to balance these factors
to improve comparability. Cox multivariate analyses were performed using
the following factors: age, surgical approach, FIGO stage, positive
vaginal margins, parametrial involvement, tumor diameter, deep stromal
invasion, and lymphovascular space invasion (LVSI).

\textbf{Statistical Analysis}

Statistical analysis was performed by using SPSS 22.0 statistical
software (SPSS, Inc., Chicago, IL, USA). Two independent samples t-tests
were used for continuous variables, and X \textsuperscript{2} tests or
nonparametric tests were used for categorical variables. The log-rank
test in the Kaplan-Meier (KM) method was used to compare the 5-year
oncological outcomes (OS and DFS) between the two groups. Cox
proportional hazards regression models were used to calculate hazard
ratios (HR) and 95\% confidence intervals (CI) for multivariate
analysis. A p values \textless{}0.05 was regarded as significant. All
statistical methods and statistical procedures used in this study were
reviewed by statisticians.

\textbf{Results}

In total, 549 eligible patients with early-stage adenocarcinoma of the
uterine cervix in FIGO 2018 underwent ORH or LRH and were followed up
during the study period; 314 and 235 patients underwent ORH and LRH,
respectively and 223 patients were enrolled in each group after
matching. (Figure 1) Table 1 shows the tumor characteristics in the two
groups including unadjusted analysis and adjusted analysis. Mean ages
were similar (unadjusted: 46.27 versus 46.75 years, P = 0.563; adjusted:
46.04 versus 46.83 years, P = 0.380). There were no other between-group
differences in FIGO stage distribution, tumor size, intermediate (LVSI)
and high (parametrial involvement and resection margin involvement) risk
factors, while difference existed in cervical stromal invasion between
the two groups in unadjusted analysis. (Table 1)

The mean operating time in ORH was shorter than LRH both in unadjusted
analysis and adjusted analysis (unadjusted: 211.7 versus 236.7 min,
P\selectlanguage{english}<0.001; adjusted: 214.8 versus 240.3 min, P\selectlanguage{english}<0.001), but estimated
blood loss (unadjusted: 355.0 versus 161.5 ml, P \textless{} 0.001;
adjusted: 361.2 versus 165.3 ml, P \textless{} 0.001) were significantly
higher in the ORH group (Table 2). The mean anal exhaust time
(unadjusted: 2.8 versus 2.5 days, P = 0.002; adjusted: 2.8 versus 2.5
days, P = 0.003) was significantly shorter in the LRH group.

The rates of intraoperative complications and postoperative
complications between the two groups were similar both in unadjusted
analysis and adjusted analysis(Table 3). The rate of ureter injury was
higher in the LRH group (unadjusted: 0.6\% versus 3.4\%, P = 0.016;
adjusted: 0.4\% versus 3.6\%, P = 0.018) while rates of lymphocele
(unadjusted: 1.9\% versus 0\%, P = 0.033; adjusted: 1.8\% versus 0\%, P
= 0.045) and postoperative retention of urine(unadjusted: 7.3\% versus
1.7\%, P = 0.003; adjusted: 8.5\% versus 1.8\%, P = 0.001) were
significantly higher in the ORH group.

Survival outcomes had no difference between the two groups either in
unadjusted analysis or in adjusted analysis. The rates of 5-year overall
survival in ORH and LRH groups were 97.4\% and 93.8\% in unadjusted
analysis(P=0.175),97.6\% and 93.5\% in adjusted analysis(P = 0.151),
respectively, 5-year disease-free survival in ORH and LRH groups were
93.4\% and 87.8\% in unadjusted analysis(P=0.698),93.9\% and 87.2\% in
adjusted analysis(P = 0.520), respectively. (Figure 2 and 3)

The between-group differences in overall survival and disease-free
survival in subgroups divided by mean age (age \selectlanguage{english}[?] 46 years and age
\textgreater{} 46 years), tumor size (tumor size\selectlanguage{english}[?]2cm and tumor size
\textgreater{}2cm) and risk for recurrence (low-, intermediate-, and
high-risk groups) were further analyzed. No significant differences were
observed between LRH and ORH in overall survival survival and
disease-free survival in any of these subgroups (Table 4).

\textbf{Discussion}

Based on the clinical diagnosis and treatment for cervical cancer in
mainland China (Four C) database, we compared the oncological outcomes
of LRH and ORH for FIGO2018 early-stage adenocarcinoma cervical cancer
in this study. We found that LRH showed similar 5-year DFS and OS rates
to ORH both in the unadjusted analysis and in the adjusted analysis. In
addition, we observed that LRH is associated with lower blood loss and
shorter anal exhaust time in comparison to ORH; while no differences in
intraoperative complications and postoperative complications exist. LRH
is not only an oncologically safe alternative to ORH but a preferred
method of surgical management for early-stage adenocarcinoma in FIGO
2018 of the uterine cervix.

Laparoscopic surgery has become popular and widely used since 1990, when
the Nezhat reported the complete laparoscopic
hysterectomy\textsuperscript{{[}23{]}}. In recent years, some
retrospective studies have compared the oncological outcomes of
laparoscopic surgery and open surgery\textsuperscript{{[}10, 11, 13,
14{]}}\selectlanguage{english},and the results of these studies all concluded that the
oncological outcomes of laparoscopic surgery and open surgery were
similar, which was consistent with the results of our study. The results
of the LACC trial published in 2018 indicated that among patients with
early-stage cervical cancer, the 4.5-year disease-free survival rate in
the minimally invasive surgery group was 86\%, while that in the
laparotomy group was 96.5\%. The 3-year survival rate of patients in the
minimally invasive surgery group was significantly lower than that of
the laparotomy group (93.8\% vs. 99.0\%), the mortality rate (4.4\% vs.
0.6\%) and the local recurrence rate were higher than those in the
laparotomy group\textsuperscript{{[}24{]}}. A multi-center retrospective
study reported in the same period found that the mortality rate of
patients with stage \selectlanguage{english}IA2 and \selectlanguage{english}IB1 cervical cancer treated by laparoscopic
surgery was significantly higher than that of open surgery. The
4-year-related survival rate for cervical cancer decreased by an average
of 0.8\% per year since laparoscopic surgery was used in
2006.\textsuperscript{{[}25{]}} The reason for the inconsistency with
the LACC results may be that only the histological type of cervical
adenocarcinoma was included in this study.

Consistent with the results of other studies\textsuperscript{{[}10, 11,
14, 26-30{]}}\selectlanguage{english},we observed that LRH was associated with lower blood loss
and shorter anal exhaust time in comparison to ORH, while the operation
time in LRH was significantly longer than that in ORH, which may be
related to the operation steps of laparoscopic surgery, such as using
the uterine cup; using a specimen bag to remove lymph nodes; using
laparoscopic instruments to suture the vaginal stump and other related
operations would increase the operation time.

We found that in patients with early-stage cervical adenocarcinoma, the
incidence of intraoperative and postoperative complications was similar
in LRH and ORH either in the unadjusted analysis or in the adjusted
analysis (intraoperative complications: unadjusted: 5.5\% vs. 2.5\% ,
P=0.391; adjusted: 5.8\% vs. 2.7\%, P=0.101; postoperative
complications: unadjusted: 6.7\% vs. 6.0\%, P=0.729; adjusted: 5.8\% vs.
6.3\%, P=0.843) , which is consistent with the results of previous
studies\textsuperscript{{[}11, 27, 30, 31{]}}. However, the results of
J.-H. Nam et al. found that the incidence of postoperative complications
in LRH was lower than that in ORH (9.2\% VS 21\%,
P\textless{}0.001)\textsuperscript{{[}10{]}}\selectlanguage{english},especially the incidence
of postoperative fever and postoperative pelvic abscess. The reason for
the difference may be that the cases included in this study was from
1997 to 2008, when the aseptic principle of surgical operation and the
standardization of surgical operation may not have been strictly
controlled. Jeong-Yeol Park et al. also indicated that the incidence of
postoperative complications in the laparoscopic group was significantly
higher than that in the laparotomy group (14.0\% VS 34.6\%, P
\textless{} 0.001)\textsuperscript{{[}14{]}}\selectlanguage{english},including the incidence of
postoperative wound dehiscence, pelvic abscess, postoperative intestinal
obstruction, which was mainly related to the laparotomy operation.
Different from the results of the above studies, we found that the
incidence of postoperative retention of urine in ORH was significantly
higher than that in LRH both in the unadjusted analysis and in the
adjusted analysis (unadjusted: 7.3\% VS 1.7\%, P=0.003; adjusted: 8.5\%
VS 1.8\%, P=0.001), possibly because the mean time of removal of Foley
catheter in ORH was shorter than that in LRH (unadjusted: 9.3 days VS
10.4 days, P=0.023; adjusted: 9.4 days vs 10.5 days, P=0.046). Under the
premise of the same surgical scope, premature removal of the urinary
catheter may be detrimental to postoperative bladder function recovery.

Based on the Four C database, our study uses 1:1 propensity score
matching method to match variables that may affect postoperative
survival outcomes, and discusses the indications of laparoscopic surgery
for early stage cervical adenocarcinoma from the perspective of
oncology, which provides a reference for the surgical treatment of
adenocarcinoma. However, this study still has certain limitations.
First, the data collected in the retrospective study have certain
confounding factors and selection bias. Second, the experience of the
surgeons from different hospitals may vary in this study, which may have
an effect on the prognosis. Third, the LRH in our study had more type C
hysterectomies and fewer type B hysterectomies than the ORH, but
previous studies have shown that QM-B hysterectomy and QM-C hysterectomy
have similar survival outcomes\textsuperscript{{[}32-35{]}}. Fourth,
although we used 1:1 propensity score matching method to balance
confounding factors between the LRH and ORH, we could not include all
factors that might have an influence on the prognosis. Finally, there
are fewer cases of death and recurrence due to the early-stage cervical
adenocarcinoma.

To sum up, our study suggests that there were no statistically
significant differences both in postoperative oncological outcomes and
complications between the LRH and ORH in patients with early-stage
cervical adenocarcinoma. Therefore, LRH may be an appropriate option for
early-stage cervical adenocarcinoma when compared with ORH. More large
sample prospective cohort studies are needed to confirm the role of LRH.

\textbf{Acknowledgements}

We thank Min Hao (The Second Hospital of Shanxi Medical University),
Wuliang Wang (The Second Affiliated Hospital of Zhengzhou University),
Shan Kang (The Fourth Hospital of Hebei Medical University), Bin Ling
(China--Japan Friendship Hospital), Lixin Sun and Hongwei Zhao (Shanxi
Cancer Hospital), Jihong Liu and Lizhi Liang (Sun Yat-sen University
Cancer Center), Lihong Lin and Yu Guo (Anyang Tumor Hospital), Li Wang
(The Affiliated Tumor Hospital of Zhengzhou University), Weidong Zhao
(Anhui Provincial Cancer Hospital), Yan Ni (The Yuncheng Central
Hospital of Shanxi Province), Wentong Liang and Donglin Li (Guizhou
Provincial People's Hospital), Jianxin Guo (Daping Hospital, The Third
Military Medical University), Shaoguang Wang (The Affiliated Yantai
Yuhuangding Hospital of Qingdao University), Xuemei Zhan and Mingwei Li
(Jiangmen Central Hospital), Weifeng Zhang (Ningbo Women \& Children's
Hospital), Peiyan Du (The Affiliated Cancer Hospital and Institute of
Guangzhou Medical University), Ziyu Fang (Liuzhou Workers' Hospital),
Rui Yang (Shenzhen Hospital of Peking University), Long Chen (Qingdao
Municipal Hospital), Encheng Dai and Ruilei Liu (Linyi People's
Hospital), Yuanli He and Mubiao Liu (Zhujiang Hospital, Southern Medical
University), Jilong Yao and Zhihua Liu (Shenzhen Maternity \& Child
Health Hospital), Xueqin Wang (The Fifth Affiliated Hospital of Southern
Medical University), Anwei Lu (Maternal and Child Health Hospital of
Guiyang Province), Shuangling Jin (Peace Hospital affiliated to Changzhi
Medical College), Yan Xu (Guangzhou Pan Yu Central Hospital), Ben Ma
(Guangzhou First People's Hospital), Zhonghai Wang (Shenzhen Nanshan
People's Hospital), Lin Zhu (The Second Hospital of Shandong
University), Hongxin Pan (The Third Affiliated Hospital of Shenzhen
University), Qianyong Zhu (No. 153 Center Hospital of Liberation
Army/Hospital No. 988 of the Chinese People's Liberation Army Joint
Support Force), Dingyuan Zeng and Zhong Lin (Maternal and Child Health
Care Hospital of Liuzhou), Xiaohong Wang (Laiwu People's Hospital/Jinan
City People's Hospital), and Bin Zhu (The Affiliated Yiwu Women and
Children Hospital of Hangzhou Medical College) for their contribution in
data collection.

\textbf{Funding}

This study was supported by the National Science and Technology Support
Program 252 of China (2014BAI05B03); the National Natural Science Fund
of Guangdong 253 (2015A030311024) and the Science and Technology Plan of
Guangzhou (158100075).

\textbf{Disclosure}

The authors declare no conflict of interest.

\textbf{Contribution to Authorship}

Zhaohong Yin\selectlanguage{english},Zhumei Cui and Shan Kang are contributed equally to this
work.

Zhaohong Yin conceived, designed and supervised the the study,
interpreted the data, developed and revised the manuscript

Zhumei Cui conceived, designed and supervised the the study, interpreted
the data, developed and revised the manuscript.

Shan Kang conceived, designed and supervised the the study, interpreted
the data, developed and revised the manuscript.

Chunlin Chen conceived and designed the study,interpreted the data,
developed and revised the manuscript.

Ping Liu conceived and designed the study,interpreted the data,
developed and revised the manuscript.

Mei Ji conceived, designed the study, data collection,interpreted the
data.

Wentong Liang conceived, designed the study, assisted in data
collection.

Biliang Chen conceived, designed the study, assisted in data collection.

Xuemei Zhan conceived, designed the study, assisted in data collection.

Yi Zhang conceived, designed the study, assisted in data collection.

Weidong Zhao conceived, designed the study, assisted in data collection.

Yuanli He conceived, designed the study, assisted in data collection.

Weili Li did the data analysis and interpretation.

Zhifeng Huo did the data analysis and interpretation.

\textbf{Details of ethics approval}

This multicenter retrospective study was approved by the ethics
committee of the Nanfang Hospital of Southern Medical University (No.
NFEC-2017-135) and was registered with the International Clinical Trials
Registry Platform Search Port (https://apps.who.int/trialsearch/),
clinical trial registration number CHiCTR1800017778.

\textbf{References}

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\textbf{Hosted file}

\verb`image1.emf`  available at \url{https://authorea.com/users/372558/articles/570818-laparoscopic-versus-open-radical-hysterectomy-in-early-stage-cervical-adenocarcinoma-in-figo2018-long-term-survival-outcomes-after-propensity-score-matching}

Fig.1 Flowchart of patients included in the analysis.

Table 1. Tumor characteristics of patients with cervical cancer\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
Characteristics & Before matching & Before matching & P value & After
matching & After matching & P value\tabularnewline
& ORH(n=314) & LRH(n=235) & & ORH(n=223) & LRH(n=223) &\tabularnewline
Age & 46.27\selectlanguage{ngerman}±9.501 & 46.75\selectlanguage{ngerman}±9.783 & 0.563 & 46.04\selectlanguage{ngerman}±9.401 & 46.83\selectlanguage{ngerman}±9.788 &
0.380\tabularnewline
Tumor size (cm) & & & 0.488 & & & 1.000\tabularnewline
[?]2cm & 165(52.5\%) & 137(58.3\%) & & 125(52.5\%) & 125(58.3\%)
&\tabularnewline
>2cm & 149(47.5\%) & 98(41.7\%) & & 98(43.9\%) & 98(43.9\%)
&\tabularnewline
FIGO stage(2018), n (\%) & & & 0.718 & & & 0.444\tabularnewline
IA2 & 10(3.2\%) & 7(3.0\%) & & 10(4.5\%) & 6(2.7\%)
&\tabularnewline
IB1 & 147(46.8\%) & 121(51.5\%) & & 108(48.4\%) & 112(50.2\%)
&\tabularnewline
IB2 & 129(41.1\%) & 90(38.3\%) & & 83(37.2\%) & 90(40.4\%)
&\tabularnewline
IIA1 & 28(8.9\%) & 17(7.2\%) & & 22(9.9\%) & 15(6.7\%)
&\tabularnewline
Depth of cervical stromal invasion, n (\%) & & & 0.045 & & &
1.000\tabularnewline
Less than half & 213(67.8\%) & 147(63.2\%) & & 147(65.9\%) &
147(65.9\%) &\tabularnewline
More than half & 58(18.5\%) & 37(16.2\%) & & 37(16.6\%) &
37(16.6\%) &\tabularnewline
Not reported & 43(13.7\%) & 51(20.6\%) & & 39(17.5\%) &
39(17.5\%) &\tabularnewline
Lymphovascular space invasion, n (\%) & & & 0.544 & & &
0.401\tabularnewline
Absent & 299(95.1\%) & 221(93.9\%) & & 213(95.1\%) & 209(93.9\%)
&\tabularnewline
Present & 15(4.9\%) & 14(6.1\%) & & 10(4.9\%) & 14(6.1\%)
&\tabularnewline
Parametrial involvement, n (\%) & & & 0.082 & & & 0.156\tabularnewline
Absent & 310(98.7\%) & 235(100.0\%) & & 221(98.7\%) &
223(100.0\%) &\tabularnewline
Present & 4(1.3\%) & 0(0.0\%) & & 2(1.3\%) & 0(0.0\%)
&\tabularnewline
Resection margin involvement, n (\%) & & & 0.760 & & &
1.000\tabularnewline
Absent & 309(98.4\%) & 232(98.7\%) & & 220(98.7\%) & 220(98.7\%)
&\tabularnewline
Present & 5(1.6\%) & 3(1.3\%) & & 3(1.3\%) & 3(1.3\%)
&\tabularnewline
Postoperative adjuvant treatment & & & 0.472 & & & 0.564\tabularnewline
None & 292(92.8\%) & 220(93.4\%) & & 209(92.8\%) & 208(93.4\%)
&\tabularnewline
RT & 2(0.7\%) & 0(0.0\%) & & 1(0.7\%) & 0(0.0\%)
&\tabularnewline
CCRT & 20(6.6\%) & 15(6.6\%) & & 13(6.6\%) & 15(6.7\%)
&\tabularnewline
\bottomrule
\end{longtable}

\emph{ORH open radical hysterectomy; LRH laparoscopic radical
hysterectomy; FIGO International Federation of Obstetrics and
Gynecology; RT radiation therapy; CCRT concurrent chemoradiation
therapy}

Table 2. Operative details and postoperative recovery\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Before matching\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Before matching\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
P value\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
After matching\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
After matching\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
P value\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ORH(n=314)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
LRH(n=235)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
ORH(n=223)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
LRH(n=223)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Operating time (min), mean (range)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
211.7(75.0-400.0)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
236.7(80.0-600.0)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textbf{<0.001}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
214.8(95.0-400.0)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
240.3(115.0-600.0)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textbf{<0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Preoperative hemoglobin level (gm/dl), mean (range)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
124.6(74.0-355.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
126.2(81.0-500.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.446\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
124.4(82.0-172.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
126.6(81.0-500.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.331\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Blood loss (ml), mean (range)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
355.0(20.0-1800.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
161.5(10.0-1500.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{<0.001}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
361.2(50.0-1800.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
165.3(10.0-1500.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{<0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
anal exhaust time (days), mean (range)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.8(1.0-6.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.5(1.0-9.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.002}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.8(2.0-6.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.5(1.0-9.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.003}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Return of bowel movement (days), mean (range)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4.2(2.0-10.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4.1(1.0-11.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.476\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4.3(2.0-10.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4.2(1.0-11.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.453\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Removal of Foley catheter (days), mean (range)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
9.3(3.0-70.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
10.4(3.0-33.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.023}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
9.4(3.0-70.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
10.5(3.0-33.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.046}\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Table 3. Intra- and postoperative complications within 60 days after
surgery\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
& Before matching & Before matching & P value & After matching & After
matching & P value\tabularnewline
& ORH(n=314) & LRH(n=235) & & ORH(n=223) & LRH(n=223) &\tabularnewline
Intraoperative complications, n (\%) & 8(2.5) & 13(5.5) & 0.391 &
6(2.7) & 13(5.8) & 0.101\tabularnewline
Great vessel injury & 0(0.0) & 1(0.4) & 0.247 & 0(0.0) & 1(0.4)
& 0.317\tabularnewline
Ureter injury & 2(0.6) & 8(3.4) & \textbf{0.016} & 1(0.4) &
8(3.6) & \textbf{0.018}\tabularnewline
Obturator nerve injury & 0(0.0) & 1(0.4) & 0.247 & 0(0.0) &
1(0.4) & 0.317\tabularnewline
Bladder injury & 5(1.6) & 3(1.3) & 0.760 & 4(1.8) & 3(1.3) &
0.703\tabularnewline
Other intraoperative complications & 1(0.3) & 0(0.0) & 0.387 &
1(0.4) & 0(0.0) & 0.317\tabularnewline
Postoperative complications & 21(6.7) & 14(6.0) & 0.729 & 13(5.8)
& 14(6.3) & 0.843\tabularnewline
Deep vein thrombosis & 2(0.6) & 2(0.9) & 0.770 & 2(0.9) & 2(0.9)
& 1.000\tabularnewline
Febrile morbidity & 2(0.6) & 5(2.1) & 0.123 & 1(0.4) & 5(2.2) &
0.100\tabularnewline
Ileus & 1(0.3) & 0(0.0) & 0.387 & 1(0.4) & 0(0.0) &
0.317\tabularnewline
Lymphedema & 1(0.3) & 0(0.0) & 0.387 & 1(0.4) & 0(0.0) &
0.317\tabularnewline
lymphocele & 6(1.9) & 0(0.0) & \textbf{0.033} & 4(1.8) & 0(0.0)
& \textbf{0.045}\tabularnewline
vesicovaginal fistula & 0(0.0) & 2(0.6) & 0.220 & 0(0.0) &
1(0.4) & 0.317\tabularnewline
ureterovaginal fistula & 0(0.0) & 1(0.4) & 0.247 & 0(0.0) &
1(0.4) & 0.317\tabularnewline
recto-vaginal fistula & 0(0.0) & 1(0.4) & 0.247 & 0(0.0) &
1(0.4) & 0.317\tabularnewline
Wound dehiscence & 2(0.6) & 0(0.0) & 0.220 & 1(0.4) & 0(0.0) &
0.317\tabularnewline
Vaginal cuff infection & 0(0.0) & 1(0.4) & 0.247 & 0(0.0) &
1(0.4) & 0.317\tabularnewline
Postoperative bleeding & 0(0.0) & 1(0.4) & 0.247 & 0(0.0) &
1(0.4) & 0.317\tabularnewline
Other postoperative complications & 9(2.9) & 3(1.3) & 0.208 &
5(2.2) & 3(1.3) & 0.476\tabularnewline
Postoperative retention of urine & 23(7.3) & 4(1.7) & \textbf{0.003}
& 19(8.5) & 4(1.8) & \textbf{0.001}\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

Fig. 2a Overall survival rates before matching Fig. 2b Disease-free
survival rates before matching\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image4/image4}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image5/image5}

\end{center}
\end{figure}

Fig. 3a Overall survival rates after matching . Fig. 3b Disease-free
survival rates after matching

Table 4. Cox regression analysis of disease-specific survival and
recurrence-free survival in patients\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
& & Disease-specific survival & Disease-specific survival &
Recurrence-free survival & Recurrence-free survival\tabularnewline
& & HR(95\%CI) & P-value & HR(95\%CI) & P-value\tabularnewline
Age & Age[?]46 years & 1.361(0.220-8.410) & 0.740 & 2.183(0.585-8.144)
& 0.245\tabularnewline
& Age>46years & 5.375(0.576-50.139) & 0.140 & 1.096(0.311-3.868) &
0.886\tabularnewline
Tumor size & [?]2cm & 2.850(0.245-33.218) & 0.403 & 1.161(0.338-3.992)
& 0.813\tabularnewline
& >2cm & 2.698(0.535-13.605) & 0.229 & 1.900(0.486-7.425) &
0.356\tabularnewline
Risk group & Low risk group & 1.948(0.263-14.455) & 0.514 &
1.778(0.549-5.755) & 0.337\tabularnewline
& Intermediate risk group & 2.482(0.431-14.273) & 0.309 &
1.092(0.260-4.584) & 0.904\tabularnewline
& High risk group & 1.000(0.012-80.730) & 1.000 &
1.000(0.012-80.730) & 1.000\tabularnewline
Total & & 2.624(0.784~8.778) & 0.117 & 1.323(0.578~3.029) &
0.508\tabularnewline
\bottomrule
\end{longtable}

\textbf{Hosted file}

\verb`6.Figures.docx`  available at \url{https://authorea.com/users/372558/articles/570818-laparoscopic-versus-open-radical-hysterectomy-in-early-stage-cervical-adenocarcinoma-in-figo2018-long-term-survival-outcomes-after-propensity-score-matching}

\selectlanguage{english}
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\end{document}

