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.
  1. 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.
  2. Methods
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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