Abstract
Objective Explore the difference of oncology outcome of
laparotomy and laparoscopy in the new FIGO2018 stage of early cervical
squamous cell carcinoma without any high risk pathological factors.
Methods The 5-years OS and DFS of cervical squamous cell
carcinoma undergoing laparotomy and laparoscopy from 2004 to 2018 were
compared by the total study population and propensity score from China.
Result There was no difference in 5-year OS between laparotomy
(2,478 cases) and laparoscopy (1,504 cases), but the 5-year DFS of
laparotomy was higher (92.2 %vs. 90.4%, P=0.022). Cox analysis showed
that laparoscopy was not an independent risk factor for the death of
cervical squamous cell carcinoma (OS: P=0.598), but it was an
independent risk factor for the recurrence/death (HR = 1.468,95% CI
1.131 ~ 1.906, P=0.004). There was no difference in
5-year OS between laparotomy (2,391 cases) and laparoscopy (1,495 cases)
after 1:2 PSM, but the 5-year DFS of laparotomy was higher (92.7% vs.
90.8%, P = 0.006), Cox analysis showed that laparoscopy was not an
independent risk factor for the
death of cervical squamous cell carcinoma (OS: P=0.521), but it was an
independent risk factor for the recurrence/death (HR=1.512, 95%CI
1.151~1.971, P=0.002).
Conclusion There is no difference in 5-year OS between these
groups for early cervical squamous cell carcinoma in new stage of
FIGO2018 without any high-risk pathological factors, the 5-year DFS of
laparotomy is higher than that of laparoscopy group, and laparoscopy is
an independent risk factor for recurrence/death, so
laparoscopy has a higher risk of
recurrence.
Key words : Cervical cancer;
Laparotomy; Laparoscopy; Tumor outcome; no high-risk factors after
surgery.
- IntroductionA multicenter laparoscopic cervical cancer surgery (LACC) study
published in New England Journal of Medicine in October, 2018 pointed
out that the overall survival rate (OS) and disease-free survival rate
(DFS) of cervical cancer patients who underwent laparoscopic surgery
in stage ⅠA1(LVSI+)~ⅠB1 were lower than those who
underwent open surgery, and had a higher local recurrence rate[1]. A real-world study published in the same
period further confirmed this conclusion. Minimally invasive surgery
is associated with a worse oncology prognosis[2]. This is contrary to previous related
research and has caused widespread international controversy. In 2020,
national comprehensive cancer network (NCCN) cervical cancer guideline[3] changed open surgery to the standard
surgical approach. Later, many studies thought that there was no
difference in oncology outcome between laparotomy and laparoscopic
surgery for some cervical cancer staging [4-5].
In the limitations of LACC research, it was mentioned that this
research failed to further analyze the differences of oncology
outcomes between the two surgical approaches possibly caused by
pathological factors, and the conclusion could not be extended to the
oncology outcomes of low-risk cervical cancer patients. The cases
included in this study include squamous cell carcinoma, adenocarcinoma
and adenosquamous carcinoma. However, in recent years, the research
results on the oncological outcome and prognosis of cervical squamous
cell carcinoma and adenocarcinoma are inconsistent. Some studies think
that there is no difference between them [6-8],
and some studies think that adenocarcinoma has a worse oncological
outcome and a higher recurrence rate than squamous cell carcinoma[9-10]. Noh et al. [6]found that histological type was the only independent risk factor for
cervical cancer in IB1~IIA stage. The staging of LACC
study is limited to FIGO2009 staging ⅰ A1 (LVSI+) ~ ⅰ
B1 cervical cancer cases, and NCCN guidelines indicate that cervical
adenocarcinoma may be a new ”medium risk factor”. Then, whether the
conclusion of this study is equally applicable to the new stage early
cervical squamous cell carcinoma of FIGO2018 without any high-risk
pathological factors, and what is the oncological prognosis of such
patients undergoing laparotomy/laparoscopy? At present, there is still
a lack of multi-center large sample research.
Therefore, this study is based on the clinical diagnosis and treatment
for cervical cancer in China (Four
C) to screen out the cases of early cervical squamous cell carcinoma
in the new stage of FIGO2018 who underwent laparotomy/laparoscopy, and
compare the oncology outcomes of the patients who underwent laparotomy
and laparoscopy by the total study population and propensity score
matching.
- Methods
- Data CollectionFour C adopted a multicenter, retrospective cohort study, which was
approved by the ethics committee of Nanfang Hospital, Southern
Medical University (ethics No. NFEC-2017-135) and international
clinical trial registration No. CHiCTR1800017778 International
Clinical Trials Registry Platform Search
Port,http//apps.who.int/trialsearch/). See the published articles of
our team for data collection methods [11-14].
Due to the long time span of entering cases, the cases before 2009
in this database are staged according to FIGO1994, and the cases
after 2009 are staged according to FIGO2009. After all cases are put
into storage, the staging shall be corrected again according to the
revised version of FIGO2018.
- Inclusion and Exclusion CriteriaInclusion criteria: (1) age ≥ 18 years old; (2) Pathological
diagnosis of cervical cancer by cervical biopsy; (3) Postoperative
histopathological type of squamous cell carcinom; (4) There was no
adjuvant treatment before operation; (5) FIGO stage (2018): IA2,
IB1, IB2, IIA1; (6) Surgical approach: laparotomy / laparoscopy; (7)
QM-B or QM-C hysterectomy, pelvic lymphadenectomy±para-aortic
lymphadenectomy/biopsy; (8) The postoperative pathological report
was complete, with lymph node status and negative; (9) No other
high-risk pathological factors; (10) No adjuvant treatment after
operation; (11) Follow-up.
Exclusion criteria: (1) do not meet the above inclusion criteria;
(2) Pregnancy complicated with cervical cancer, stump cancer or
other malignant tumors.
- Propensity Score MatchingIn order to eliminate the influence of baseline differences, this
paper will include the following variables for propensity score
matching (PSM): age and FIGO stage (2018) make the baseline balance
between groups and reduce the influence of possible bias and
confounding factors.
- Observation IndicatorsThe main long-term oncological outcome indicators were OS and DFS.
The fifth year after the operation was taken as the cut-off point.
OS was defined as the date of diagnosis to death of any cause or the
last effective follow-up; DFS was defined as death/recurrence of any
cause or the last effective follow-up from the date of diagnosis to
the occurrence of any cause.
- Statistical AnalysisSPSS 23.0 software (IBM Corporation, Armonk, NY, USA) was used for
statistical analysis. The measurement data are expressed as the mean
± standard deviation, Student’s t-test was used for inter-group
comparisons, the counting data are expressed as percentages (%),
and the inter-group rates were compared by the chi-square test or
Fisher’s exact probability method. The follow-up time was expressed
as the median; survival curves for the two groups were generated by
the Kaplan-Meier (K-M) method and compared by the log-rank test; the
independent risk factors were analysed by a multi-factor Cox
regression model, and the related hazard ratios and confidence
intervals were calculated. The PSM score was determined by a logical
regression model. Differences with P < 0.05 were
considered statistically significant. The specific statistical
methods can be found in the articles published by our team[7-10].3.Results 3.1 Study PopulationData for a total of 63926 patients with cervical cancer in 47
hospitals in China from 2004 to 2018 were collected. Among them,
2478 patients aged 47.72 ± 10.090 years underwent laparotomy, and
1504 patiens aged 47.92 ± 9.743 years underwent laparoscopy. The
median follow-up time was 49 months
(laparotomy group vs laparoscopy
group: 57 months vs 36 months). The data filtering process is shown
in figure1.
According to the results of the baseline analysis between the two
groups, there was a significant difference in FIGO stage (2018)
between the two groups. An additional 1:2 PSM step was performed
between the two groups, and a total of 3886 patients were included
after matching. A total of 2391 patients aged 47.59 ± 10.054 years
were included in the laparotomy group. 1495 patients aged 47.93
±9.757 years were included in the laparoscopy group. The median
follow-up time was 49 months (laparotomy group vs laparoscopy group:
57 months vs 36 months). The baseline between the two groups was
balanced. (Table 1).Figure 1. Data Screening Flow ChartTable 1 Characteristics of Patients with FIGO 2018 early
Stage Cervical Cancer Before and After 1:2 PSM