4.Discussion
The results of a multicenter and retrospective study showed that there were no high-risk and high-risk pathological factors in Four C. There was no significant difference in 5-year OS between the laparotomy group and the laparoscopy group, but the 5-year DFS in the laparotomy group was higher than that in the laparoscopy group; Cox multivariate analysis showed that laparoscopic surgery was an independent risk factor for recurrence / death in patients with early cervical squamous cell carcinoma without high and medium risk factors. In order to further reduce bias and confounding factors, 1:2PMS was carried out and the same conclusion was reached.
The results of this study found that there was no difference in 5-year OS between open surgery and laparoscopic surgery, which was different from the LACC study of Ramirez et al[1], which believed that laparoscopic surgery was 4.5% for patients with stage IA1(LVSI+)~IB1 cervical cancer the 5-year OS was lower than that in the laparotomy group (86.0% vs. 96.5%). Considering the different stages of cervical cancer included, there were about 91.5% in the LACC study of Ramirez et al 9% of cervical cancer patients are in stage IB1. The stage included in this study also includes stage IIA1 cervical cancer cases. The survival analysis before and after matching in Uppal et al. [15] research showed that there was no difference in the overall survival rate of patients with stage IA1(LVSI+)~IB1 cervical cancer undergoing laparoscopic surgery and laparotomy.
In terms of DFS, it is consistent with the results of LACC. It is found that the DFS of laparoscopic surgery is lower than that of laparotomy surgery. Cox multivariate analysis suggests that laparoscopic surgery is an independent risk factor for recurrence / death of cervical cancer patients. Chenx et al. [16] found that there was no difference between the 5-year OS of laparoscopic surgery and laparotomy surgery for cervical cancer patients with stage IB1 in FIGO 2009, but the 5-year DFS was significantly lower than that of laparotomy group. Cox multivariate analysis showed that laparoscopic surgery was associated with lower tumor-free survival rate, which was consistent with the results of this research, but the study did not conduct postoperative pathological review of surgical specimens and the sample size was limited, This may cause selection bias and confounding factors.
Different from the results of this study, Ratiud et al.[17] analyzed the cervical cancer patients who underwent laparotomy surgery or laparoscopic surgery in figo2009 stage IA1 ~ IIB and found that there was no significant difference in 5-year OS between the laparoscopic group and the laparotomy group (94.1% vs 85.4% P = 0.311), but found that the 5-year DFS in the laparoscopic group was higher than that in the laparotomy group (94.1% vs 75.6% P = 0.049), It is considered that minimally invasive surgery for patients with stage IA1 ~ IIB cervical cancer can improve the tumor-free survival rate. This is different from the results of this study. The reasons are as follows: first, this study does not strictly limit the presence or absence of adjuvant therapy and the number of times before operation. Second: the difference between the two groups was statistically significant in terms of baseline lymphatic vascular infiltration. However, due to the small number of cases included in the study, a total of 75 cases were not controlled by PSM. Third: the histological types of the study are different. In addition to squamous cell carcinoma, the study also includes adenocarcinoma and adenosquamous cell carcinoma. Fourth: the study stage is figo2009 stage IA1 ~ IIB, which is not specifically for early cervical cancer cases.
At present, the conclusions of oncological prognosis of laparotomy and laparoscopy are different in patients with different histological types of cervical cancer. Kimsi [18] found that when the histological type is cervical squamous cell carcinoma, the 5-year PFS of laparoscopic surgery is lower than that of laparotomy surgery, but there is no difference between the two groups in non cervical squamous cell carcinoma, while other studies found no difference in oncological outcomes between the two subtypes [6-8,19]. Leeyy[10] included 775 cases of stage IB ~ IIA cervical cancer in FIGO2009, including 636 cases of squamous cell carcinoma and 139 cases of adenocarcinoma. The results showed that compared with squamous cell carcinoma, adenocarcinoma before and after matching was associated with worse survival outcome and higher distant recurrence rate. Mabuchis et al. [20]found that the prognosis of cervical adenocarcinoma is worse than that of cervical squamous cell carcinoma when there are any high and medium risk pathological factors. When the histological type is adenocarcinoma, it may affect the oncological outcome of laparotomy surgery and laparoscopic surgery. In order to make this study more convincing, the histological type is limited to cervical squamous cell carcinoma, and whether the postoperative adjuvant treatment is standardized due to high-risk pathological factors will lead to the difference of oncological outcome between the two groups. Therefore, this study limits the pathological factors and carries out PSM to control the confounding factors, The results before and after matching showed that laparoscopic surgery had worse oncological outcomes.
Patients with cervical cancer undergoing laparoscopic surgery have a high recurrence rate, which may be related to the failure to strictly implement the tumor free principle during the operation, the promotion of inflammation and tumor metastasis by CO2 pneumoperitoneum during the operation, the use of uterine lifting device during the operation, the gasification of electrical equipment, the way of vaginal disconnection and suture [21-24]. Vaginal uterine lifter is related to direct contact with tumor lesions and long-term compression, resulting in rupture of tumor cells and artificial diffusion of tumor cells.
This study has some limitations. Firstly, the case data of 47 hospitals in China are included in this study, which will lack some clinical data. Secondly, there are some deviations in the surgical level and experience of surgeons. Third, the time span of case inclusion is long, and the surgeon’s learning curve should also be one of the factors to be considered. Although there are some defects in our study, based on the multi center large sample study, it can effectively reflect the practical value of figo2018 new stage in the diagnosis and treatment of cervical cancer in China. PSM is used to strictly control the confounding factors. At the same time, the included pathological factors are postoperative pathology, which is more accurate. Therefore, we believe that the results of this study have high reliability. This study is also a more detailed supplement to the results of previous laparoscopic and open studies, and also provides evidence support for the recommended laparoscopic surgical approach in NCCN guidelines.
In conclusion, for patients with FIGO2018 new stage early cervical squamous cell carcinoma with any high-risk pathological factors, there was no significant difference between 5-year OS of laparotomy surgery and laparoscopic surgery. 5-year DFS of laparoscopic surgery was lower than that of laparotomy surgery. Laparoscopic surgery was an independent risk factor for recurrence / death of patients with cervical cancer.