François Zaccarini

Anna Santy

Yohann Dabi

Vincent Lavoue

Xavier Carcopino

Sofiane Bendifallah

Amélie Benbara

Pierre Collinet

Geoffroy Canlorbe

Emilie Raimond

Zaccarini François

Dabi Yohann

Lavoue Vincent

Carcopino Xavier

Bendifallah Sofiane

Benbara Amelie

Collinet Pierre

Canlorbe Geoffroy

Raimond Emilie

Graesslin Olivier

Ouldamer Lobna

Darai Emile

Huchon Cyrille

François Golfier

Touboul Cyril
email: cyril.touboul@gmail.com

Bolze Pierre

Santy Anna

Amelie -Collinet Pierre

Olivier -Ouldamer Lobna

Emile Darai

Pierre Adrien

Prof Cyril Touboul

Comparison of survival outcomes between laparoscopic and abdominal radical hysterectomy for early-stage cervical cancer: A French multicentric study

Keywords: cervical cancer, radical hysterectomy, laparoscopy, open surgery, survival outcomes

INTRODUCTION

Despite prevention screening campaigns for cervical cancer and the widespread of HPV-vaccination among several countries, cervical cancer still remains the fourth most common cancer in women worldwide [START_REF] Bray | Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[END_REF].

International Federation of Gynecology and Obstetrics (FIGO) stage determines the most appropriate treatment and radical hysterectomy is currently the standard treatment for patients at early stage (2018 FIGO IA2 to IB2 and FIGO IIA1) [START_REF] Cibula | The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology Guidelines for the Management of Patients With Cervical Cancer[END_REF].

Historically, radical hysterectomy was performed by laparotomy. Along with many studies demonstrating fewer postoperative complications and shorter hospital stays, minimally invasive technics were increasingly used in the last decades [START_REF] Pomel | Laparoscopic radical hysterectomy for invasive cervical cancer: 8-year experience of a pilot study[END_REF][START_REF] Hertel | Laparoscopic-assisted radical vaginal hysterectomy (LARVH): prospective evaluation of 200 patients with cervical cancer[END_REF][START_REF] Frumovitz | Comparison of total laparoscopic and abdominal radical hysterectomy for patients with early-stage cervical cancer[END_REF]. However, unlike other types of cancer such as colorectal or endometrial cancer, equivalence in terms of cancer treatment has not been formally demonstrated [START_REF] Galaal | Laparoscopy versus laparotomy for the management of early stage endometrial cancer[END_REF][START_REF] Outcomes | A comparison of laparoscopically assisted and open colectomy for colon cancer[END_REF][START_REF] Bonjer | A randomized trial of laparoscopic versus open surgery for rectal cancer[END_REF]. This hypothesis has recently been challenged by the outstanding results of the LACC trial [START_REF] Ramirez | Minimally Invasive versus Abdominal Radical Hysterectomy for Cervical Cancer[END_REF]. In this randomized controlled trial, the patients undergoing laparoscopic surgery had a significantly higher relapse rate and significantly lower rates of diseasefree survival and overall survival than the patients undergoing open surgery. However, some comments have been reported on stages, number of laparoscopic procedures by centers as well as experience of surgeon and modalities of neoadjuvant and adjuvant therapies. Such results were unexpected by the scientific community and while the trial is well designed, it is legitimate to question the generalization of such results in European setting. Indeed, French surgeons have a long history and high experience of laparoscopy approach.

The main objective of this study was therefore to evaluate if surgical approach had an impact on surgical and oncological outcomes in patients with early-stage cervical cancer treated with radical hysterectomy in a French University Hospital setting.

MATERIAL AND METHODS

Patients and selection criteria

We conducted a retrospective study using maintained database from 9 French institutions (Creteil University Hospital, Tenon University Hospital, Pitié-Salpétrière University Hospital, Poissy University Hospital, Lille University Hospital, Tours University Hospital, Bondy University Hospital, Rennes University Hospital, and Marseille Public Hospital North, Lyon Sud Hospitals, Reims University Hospitals). These databases registered all patients diagnosed with cervical cancer at any stage between January 1996 and The following data were extracted from the medical charts: age, BMI, medical and surgical history, surgical procedure, FIGO stage, final pathological analysis, treatment received, recurrence and survival.

Patients were included whenever they were treated by radical hysterectomy. Early-stage cervical cancer are known as FIGO stage IA2 to IB2 and FIGO stage IIA1 (FIGO 2018). FIGO stages were determined on preoperative MRI. Few patients with FIGO IIB stages were included. Indeed, we noticed that a very few numbers of patients with FIGO IIB stages determined on MRI had radical hysterectomies. We chose not to eliminate them since they had radical hysterectomies and we performed a propensity score matching. The aim of a radical hysterectomy is to remove the uterus with a resection of at least 10 mm of vagina and a portion of parametrium.

The extent of the parametrium resected defines different types of radical hysterectomy. A partial resection of the uterosacral and vesicouterine ligaments were performed. The ureter was dissected and protected laterally, permitting transection of the paracervix at the level of the ureteral tunnel. Surgery could be accomplished either by laparotomy, or by a minimally invasive approach including laparoscopy or robot-assisted surgery. All patients included benefited at the same time of pelvic lymphadenectomy. Patients who had initial laparoscopy and were operated by open surgery were considered in the open surgery group.

Exclusion criteria included non-radical procedures or surgeries not performed within one of the included centers.

Were also excluded patients that benefited of a fertility-sparing surgery because the risk of relapse is higher is this population.

Pre-operative imaging work up included pelvic magnetic resonance imaging (MRI) to determine tumor size, local extension, lymph nodes involvement and FIGO stages. All stages were reassigned using the 2009 International Federation of Gynecology and Obstetrics (FIGO) since patients were registered before the publication of the new FIGO classification in 2018. Patients with cervicallimited large sized tumors (≥ 2 cm) could benefit of preoperative vaginal brachytherapy as it is sometimes performed in France.

Postoperative complications were registered and classified in four categories: urinary, vascular, digestive and other.

Initial surgical management as well as adjuvant therapies were validated in multidisciplinary committees.

Adjuvant chemotherapy or radiotherapy was proposed as recommended in patients with lymph nodes involvement, positive margins or in some cases of lymphovascular space invasion [START_REF] Cibula | The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology Guidelines for the Management of Patients With Cervical Cancer[END_REF][START_REF] Marth | Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up †[END_REF].

J o u r n a l P r e -p r o o f

Follow up was performed as recommended [START_REF] Marth | Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up †[END_REF] by clinical examination every 4 month during 2 years then every 6 month during 3 years then annually. Imaging exams were performed only in cases of suspicion of recurrence clinically.

Date of surgery was used to calculate overall survival (OS) and disease-free survival (DFS).

Statistical analysis

Databases were managed using Excel (Microsoft Corporation, Redmond, WA, USA) and statistical analyses were performed using R software and packages MatchIt and Rms (3.3.1 version, available online).

Descriptive statistics were based on the Student's t test for continuous variable and the χ 2 test or Fisher's exact test for categorical variables. The Kaplan-Meier method was used to estimate the survival distribution.

Comparisons of survival were made using the log rank test. Values of p < 0.05 were considered to denote significant differences.

Before Propensity Score Matching (PSM), two groups were constituted: patients operated by laparotomy and those operated by minimally invasive surgery (laparoscopy or robotic surgery). PSM is a statistical matching technique that attempts to estimate the effect of a certain treatment by accounting for covariates that predict receiving such treatment [START_REF] Bendifallah | Comparison of pelvic and para-aortic lymphadenectomy versus para-aortic lymphadenectomy alone for locally advanced FIGO stage IB2 to IIB cervical cancer using a propensity score matching analysis: Results from the FRANCOGYN study group[END_REF] . A propensity score was calculated using a logistic regression model, as described by Rosenbaum and Rubin and used by Sjölander in 2009 [START_REF] Sjölander | Propensity scores and M-structures[END_REF]. To adjust and optimize the matching procedure, the variables having a potential impact on the prognosis were included in the model: age at diagnosis, body mass index, histological type, FIGO stage on the preoperative MRI, tumor size defined by MRI.

Patients with missing data for the variables used in the propensity matched score were excluded as there were not many (< 5% of the cohort). Only patients with complete data for the main prognostic variables were included.

As the number of patients in our MIS group was way higher than in the laparotomy group, we decided that women would be matched (a 2:1) using the PS by an "exact" matching algorithm. To find matched women from the two groups, we adopted a caliper matching approach that can avoid bad matches (i.e., too much of a difference in PS). Once a control was matched, it was not considered again as a match for any other case (i.e., matching without replacement).

RESULTS

Characteristics of the population

J o u r n a l P r e -p r o o f

A total of 1706 patients with a cervical cancer were treated within one of the 9 university hospitals involved between 1996 and 2017. Among them, 417 patients (24.4%) underwent surgery (non-radical and radical surgeries, conservative treatments). Radical hysterectomy was performed in 264 patients: 223 underwent minimally invasive surgery (MIS) and 41 underwent open surgery. There was a difference in BMI and FIGO stages between the two groups (Table 1).

After using a propensity score matching, the minimally invasive surgery group counted 61 patients (laparoscopy and robot-assisted surgery) and the laparotomy group 32 patients. The 2 groups were comparable for the main prognostic factors of cervical cancer (Table 2).

Pre-operative brachytherapy was performed on 8 patients among which 5 had tumors ≥ 20mm., 1 patient had a 19 mm tumor (2 missing data).

Survival outcomes

There was no significant difference in overall survival: 91% in the minimally invasive surgery group and 81% in the open-surgery group (p = 0.14, CI95% 0.66 -11.9). The rate of disease-free survival at 5 years was 82% in the minimally invasive surgery group and 78% in the open surgery group (p = 0.78, CI95% 0.38 -3.6) (Figure 2).

In the minimally invasive group, there were 8 (13.1%) recurrences and 3 deaths (4.9%). The median follow-up was 39.6 months. The recurrences were mainly loco-regional (n=6). One patient had peritoneal carcinosis and 1 recurrence was at a distant site.

In the laparotomy group, there were 5 (15.6%) recurrences (15.6%) and 5 deaths (15.6%). The median followup was 57.4 months. We counted 2 loco-regional recurrences and 1 peritoneal carcinosis (the data was missing for the 2 other patients).

Intra and post-operative complications

Minimally invasive surgery was associated with a significantly shorter hospital stay than open surgery: 5.9 vs 9.0 days (p <0.01). Operating time was shorter in minimally invasive surgery without reaching a statistical significance: 228 vs 278 minutes (p = 0.17). There was no significant difference in intra and postoperative complications between the groups (Table 3).

Histopathological results

J o u r n a l P r e -p r o o f

There was no difference between the groups regarding the size of the vaginal cuff length that was around 14mm (Table 4). Negative margins were obtained in more than 80% of cases in both groups. There was a vaginal invasion in 6% of cases in both groups. There was no difference in parametrial involvement and lymph node involvement: 8.3% in the MIS group versus 15.6% in the open surgery group (Table 4). There were two surgical revisions for intestinal obstruction in the open surgery group and none in the minimally invasive surgery group. Three reoperations for disunion of the vaginal suture were recorded in the minimally invasive surgery group and none in the open surgery group.

Regarding patients who had a preoperative brachytherapy, 6 patients had no residual tumors, 1 had a 5 mm residual tumor and 1 patient had a 20 mm residual tumor (starting from a 31 mm tumor)

DISCUSSION

In this multicentric study, using a propensity score matching, no difference in overall survival and in disease-free survival was found among patients undergoing minimally invasive or abdominal radical hysterectomy for cervical cancer at early stage. The rate of overall survival at 5 years was 91% with minimally invasive surgery and 81% with open surgery. The rate of disease-free survival at 5 years was 82% with laparoscopy and 78% with open surgery. No difference in operative complication rate was noted. Hospital stay was shorter in the minimally invasive surgery group confirming its relevance from the medico-economic part.

Before November 2018, the literature was solely constituted with retrospective data and showed no difference in survival outcomes depending on the operative approach, combined with lower morbidity with minimally invasive techniques. In 2007, Frumovitz et al. [START_REF] Frumovitz | Comparison of total laparoscopic and abdominal radical hysterectomy for patients with early-stage cervical cancer[END_REF] compared 54 patients operated on laparotomy and 35 patients operated on laparoscopy (IA1 to IB3, FIGO 2018) for cervical cancer at an early stage. Despite a longer operative time, laparoscopy was associated with a reduction of blood loss, a decrease in the number of infectious complications and in hospital stay. Another retrospective study published in 2011 [START_REF] Nam | Laparoscopic versus open radical hysterectomy in early-stage cervical cancer: long-term survival outcomes in a matched cohort study[END_REF] about 263 patients operated on laparoscopy and 263 operated on laparotomy for tumors stage IA2 to IIA (FIGO 2018) , did not show any difference in 5-years recurrence free survival (92.8% and 94.4% respectively). There was a significant decrease of blood loss, hospital stay and postoperative complications. The same results were found on two meta-analysis [START_REF] Wang | Laparoscopy versus laparotomy for the management of early stage cervical cancer[END_REF][START_REF] Cao | Prognostic and Safety Roles in Laparoscopic Versus Abdominal Radical Hysterectomy in Cervical Cancer: A Meta-analysis[END_REF] but they lack of long-term data oncological outcomes.

The unexpected results of the LACC trial [START_REF] Ramirez | Minimally Invasive versus Abdominal Radical Hysterectomy for Cervical Cancer[END_REF] were largely commented and criticized. In this randomized trial, minimally invasive radical hysterectomy was associated with lower rates of disease-free and overall survival compared to open surgery. The authors hypothesized that the use of the uterine manipulator could increase the tumor cells spreading. However, uterine cannulation is also used during surgery for endometrial J o u r n a l P r e -p r o o f cancer without compromising the patient's oncological prognosis as proven by a meta-analysis evaluating the impact of uterine manipulator [START_REF] Meng | The effects of uterine manipulators in minimally invasive hysterectomy for endometrial cancer: A systematic review and meta-analysis[END_REF]. Another hypothesis is the proliferative effect of carbon dioxide on cancer cells. However, the difference of size of the vaginal cuff length depending on the surgical approach was not presented in this article.

In our study, the vaginal cuff was the same size for both groups, around 14 mm. However, it seems more difficult to assess the size of the vaginal cuff during laparoscopy than open surgery since it has been described a difference depending on the surgical approach in the literature. In a randomized trial published in 2009 [START_REF] Naik | Laparoscopic assisted radical vaginal hysterectomy versus radical abdominal hysterectomy--a randomised phase II trial: perioperative outcomes and surgicopathological measurements[END_REF], the vaginal cuff was significantly smaller in case of laparoscopy than open surgery: 1.26 vs 2.16 cm (p=0.014). A 2016 publication [START_REF] Kong | Patterns of recurrence and survival after abdominal versus laparoscopic/robotic radical hysterectomy in patients with early cervical cancer[END_REF] showed in a population of 108 patients operated on laparoscopy and 20 patients operated on robot, that performing colpotomy by laparoscopy compared to a vaginal colpotomy, was a prognostic factor for recurrence with more intraperitoneal recurrences. The intraperitoneal way of recurrence could be explained by the use of CO 2 during laparoscopy, even if the size of the "laparoscopic colpotomy" was significantly smaller: 2.2 vs 1.5 cm. There is currently no recommendation for the length of the vaginal cuff. Piver [START_REF] Piver | Five classes of extended hysterectomy for women with cervical cancer[END_REF] described in 1974, 5 different types of hysterectomy, associated with a vaginal resection ranging from 1/3 to 3/4 of the vagina. The Querleu classification only takes into account the width of the parametrial resection. The literature is also not very rich on the subject. In a study published in 2018 [START_REF] Zuo | Vaginal cuff length during radical hysterectomy is a prognostic factor for stage IB-IIA cervical cancer: a retrospective study[END_REF], a vaginal cuff smaller than 2 cm was associated with a lower relapse-free survival and overall 5-year survival and a higher local recurrence rate, compared to a vaginal cuff higher than 2 cm. The length of the vaginal cuff was an independent poor prognosis factor with FIGO stage and lymph node involvement. Another study highlighted a similar relationship: narrow cervical margins were associated with higher recurrence rates [START_REF] Viswanathan | Influence of margin status and radiation on recurrence after radical hysterectomy in Stage IB cervical cancer[END_REF]. However, Kim et al. [START_REF] Kim | Vaginal and pelvic recurrence rates based on vaginal cuff length in patients with cervical cancer who underwent radical hysterectomies[END_REF] did not find any link between the length of the vaginal cuff and the loco-regional recurrence rate. Many patients received adjuvant radiotherapy that could balance the lack of radical surgery.

Another study published in October 2018 using data from the National Cancer Registry in the United States included 2,461 patients with stage IA2 to IB1 [START_REF] Melamed | Survival after Minimally Invasive Radical Hysterectomy for Early-Stage Cervical Cancer[END_REF] cervical cancer. After using a propensity matching score, this study highlighted a higher risk of mortality at 4 years with a rate of 9.1% in patients operated on minimally invasive versus 5.3% in patients operated on laparotomy. Overall survival was also lower in case of minimally invasive surgery. Likewise, this study has found a decline in cervical cancer survival since the introduction of laparoscopy. The same type of study was carried out in endometrial cancer and it did not show this negative effect of laparoscopy [START_REF] Bregar | Minimally Invasive Staging Surgery in Women with Early-Stage Endometrial Cancer: Analysis of the National Cancer Data Base[END_REF]. This would be in favor of a specific effect in cervical cancer. A recent Korean study published in 2019 [START_REF] Kim | Comparative Effectiveness of Abdominal versus Laparoscopic Radical Hysterectomy for Cervical Cancer in the Postdissemination Era[END_REF], comparing 435 patients operated on laparotomy and 158 patients operated J o u r n a l P r e -p r o o f on minimally invasive surgery for stage IB1 to IIA2 cervical cancer, showed a higher risk of relapse in the minimally invasive surgery group without any difference in overall survival. In the multivariate analysis conducting on patients treated for IB1 stage, the minimally invasive technique was a poor prognostic factor for disease-free survival, which was not found in the context of tumors less than 2 cm. However, laparoscopy has only been practiced significantly in their center since 2012, which is far from other European practices.

In our study, among FIGO IB patients, there was the same number of patients with tumors <2cm and tumors ≥2cm but we could not perform sub-groups survival analyses. The number of patients was too low. A recent Chinese multicentric [START_REF] Chen | Comparison between robot-assisted radical hysterectomy and abdominal radical hysterectomy for cervical cancer: A multicentre retrospective study[END_REF] retrospective study showed that robot assisted radical hysterectomy was associated with a worse 3-year oncologic outcomes than abdominal radical hysterectomy. However, the oncological outcomes were similar among patients with stage IB1 and tumor size < 2cm. In a recent retrospective study from Uppal et al. [START_REF] Uppal | Recurrence Rates in Patients With Cervical Cancer Treated With Abdominal Versus Minimally Invasive Radical Hysterectomy: A Multi-Institutional Retrospective Review Study[END_REF], a worse recurrence-free survival but a similar overall survival were noted in patients undergoing minimally invasive radical hysterectomy compared with open surgery. A higher recurrence rate was also noted in patients with tumor size ≤2cm on final pathology in the minimally invasive approach. However, the size of the tumor was determined clinically. The results of an European cohort observational study (SUCCOR) comparing minimally invasive surgery versus open abdominal radical hysterectomy in patients with stage IB1 cervical cancer operated in 2013-2014 were recently presented [START_REF] Chiva | SUCCOR study. An international european cohort observational study comparing minimally invasive surgery versus open abdominal radical hysterectomy in patients with stage IB1 (FIGO 2009, <4 cm) cervical cancer operated in 2013-2014[END_REF].

Radical hysterectomy by minimally invasive surgery showed a significantly higher risk of relapse and death. However, the survival was similar in the subgroups of patients with tumors <2cm on final pathology. They also could demonstrate that the use of a uterine manipulator impacted the disease-free survival negatively. Patients that underwent radical hysterectomy by minimally invasive surgery without using a manipulator showed the same outcome that patients operated by open surgery. The information regarding the use of uterine manipulator was not available in our database.

Eventually, it is important to emphasize that assessing surgical competence and inter-operator variability is complex (especially in laparoscopy) and could largely influence prognostic as well as complications rates.

This has been studied in a recent article by Nezhat et al. [START_REF] Nezhat | Two Achilles Heels of Surgical Randomized Controlled Trials: Differences in Surgical Skills and Reporting of Average Performance[END_REF]. Indeed, in the LACC trial [START_REF] Ramirez | Minimally Invasive versus Abdominal Radical Hysterectomy for Cervical Cancer[END_REF], there was no adjustment on surgical experience or stratification according to centers or surgeons case volume, while the trial was conducted in 33 centers across 13 different countries over 9 years.

A strength of our study lies in its multicentric nature as well as in cross-checking data from patients treated in centers accustomed to the treatment of cervical cancer. The propensity score matching replicates virtually the conditions of a randomized trial and is powerful to evaluate the potential impact of surgical J o u r n a l P r e -p r o o f approach in this context. This matching was performed on preoperative characteristics to get closer to "real life" conditions. That is the reason why we did not consider the size of tumor on histological findings on our inclusion criteria. Consequently, some patients were upstaged with the histologic findings and needed adjuvant therapies.

Our study suffers other limitations. Missing data, such as vaginal preparation or the use of uterine manipulator, due to its retrospective nature could have influenced our results. Obviously, the limited number of patients that benefited from open surgery limits the extent of our conclusions. Besides, the longer follow up of these patients reflects that most patients treated with open surgery were operated in the first decade of inclusion which could also constitutes a bias. French surgeons are long used to laparoscopy and this could explain both why most patients of our cohort underwent minimally invasive approach and why we did not find any difference regarding survival in our study. Few patients with FIGO IIB stages had radical hysterectomy which we could not explain.

We decided to keep those patients since they underwent radical hysterectomies, and they were matched with the propensity score matching. The aim of this study was not to discuss the validity of the conclusions of the LACC trial but simply to investigate the survival in a french cohort based on surgical approach.

The LACC trial has certainly changed our practices. Does-it mean minimally invasive surgery should not be performed anymore? Some data suggest that this is not so simple. It is important to find a way to select properly patients that could benefit from laparoscopy. A recent study [START_REF] Anchora | How to Select Early-Stage Cervical Cancer Patients Still Suitable for Laparoscopic Radical Hysterectomy: a Propensity-Matched Study[END_REF] showed that disease free survival among patients undergoing laparoscopic surgery for tumor ≤ 20 mm was similar to patients undergoing open surgery. The case of patients at low risk of parametrial invasion (tumors less than 2cm, negative sentinel lymph node, depth of invasion less than 10 mm and no LVSI in the event of an available conization) seems less complicated. Indeed, this population could benefit from laparoscopy without worsening their oncological outcomes. Current thinking is even to offer them an extra-fascial total hysterectomy. The SHAPE trial currently underway will answer this question [START_REF]Radical Versus Simple Hysterectomy and Pelvic Node Dissection in Patients With Low-risk Early Stage Cervical Cancer (SHAPE) -Full Text View -ClinicalTrials[END_REF]. This trial is the results of 20 years of surgical aggressiveness deescalation wondering how to select patients with low risk of parametrial involvement. [START_REF] Wright | Utility of parametrectomy for early stage cervical cancer treated with radical hysterectomy[END_REF][START_REF] Dabi | Identification of a low risk population for parametrial invasion in patients with early-stage cervical cancer[END_REF] Patients with a 2 to 4 cm tumor are a more complex situation. In France, these patients can benefit from primary vaginal brachytherapy before radical hysterectomy to improve local control and reduce the use of adjuvant radiotherapy but also to reduce the extension of the parametrectomy during surgery. The management of FIGO IB patients should differ with tumor size and the 2018 FIGO classification highlighted this principle. A publication [START_REF] Escande | Outcome of early stage cervical cancer patients treated according to a radiosurgical approach: Clinical results and prognostic factors[END_REF] shown the effectiveness of such a strategy (brachytherapy followed within 6 to 8 weeks by a radical hysterectomy type B in the Querleu classification) with a recurrence-free survival rate of 93.6% in 182 IB1-IIA1 stage patients with few complications, especially urinary. Another older French study [START_REF] Ngô | Outcome in early cervical cancer following pre-operative low dose rate brachytherapy: a ten-year follow up of 257 patients treated at a single institution[END_REF] showed J o u r n a l P r e -p r o o f some equivalent results. In our study, only 8 patients underwent a preoperative brachytherapy among which 5 tumors were ≥ 2cm on MRI. It seems that there is a place for MIS without the use of the uterine manipulator after pre-operative brachytherapy. Another strategy to improve the technique of laparoscopic radical hysterectomy was proposed by Kohler et al.. The creation of a vaginal cuff enclosing the tumor and the avoidance of use of a uterine manipulator are the main characteristics of the technique [START_REF] Koehler | From laparoscopic assisted radical vaginal hysterectomy to vaginal assisted laparoscopic radical hysterectomy[END_REF]. They reported a similar survival than the laparotomy group of the LACC trial. [START_REF] Kohler | Laparoscopic radical hysterectomy with transvaginal closure of vaginal cuff -a multicenter analysis[END_REF]. Complete vaginal radical hysterectomy known as Schauta operation with laparoscopic lymphadenectomy or extraperitoneal pelvic lymphadenectomy was described [START_REF] Savino | Radical vaginal hysterectomy with extraperitoneal pelvic lymphadenectomy in cervical cancer[END_REF][START_REF] Roy | Vaginal radical hysterectomy versus abdominal radical hysterectomy in the treatment of early-stage cervical cancer[END_REF]. However, this technique has been almost abandoned and is not taught in most of University hospitals since the appearance of laparoscopic or robotic techniques.

CONCLUSION

We found no difference in survival depending on the surgical approach (minimally invasive surgery or laparotomy) for radical hysterectomy in the context of cervical cancer at an early stage. Vaginal approach for radical hysterectomy has been slowly disappearing of our practices. It might be of interest to combine good perioperative outcomes without compromising oncological results.

J o u r

  n a l P r e -p r o o f December 2017. The research protocol was approved by the Institutional Review Board (IRB) of the French College of Obstetrics and Gynecology (CEROG 2016-GYN-0502).

J o u rFIGURESFigure 1

 1 FIGURES

Figure 2 :

 2 Figure 2: Survival outcomes of minimally invasive surgery and open surgery. Red curve: open surgery. Blue curve: minimally invasive surgery. A: Overall survival, p = 0.77 B: Disease-free survival, p=0.14

  Tableau 2: Characteristics of the patients after using the propensity score matching.

			MIS	Open	p-value
			n= 61	n=32
	Age (mean)		50.8	51.8	0.74
	Body mass index (mean)		3 +/-11.7 26.1	51.0 +/-15.4 26.4	p = 0.18 0.39
	Body Mass Index (mean) Histologic type	24.6 +/-4.7	27.2 +/-6.0	p=0.008 0.66
	Histologic type Squamous cell carcinoma	43 (70.5)	23 (71.9)	p=0.47 1
	Squamous cell Adenocarcinoma	148 (66.4) 13 (21.3)	26 (63.4) 6 (18.6)	1
	carcinoma Others		5 (8.2)	3 (9.4)	1
	Adenocarcinoma Others FIGO IRM stage IA IB IIA IIB IIIA Tumor size (mm) LVSI Preoperative brachytherapy Adjuvant therapy None Brachyterapy RT-CHT* IMRT** Chemotherapy J o u r n a l P r e -p r o o f 60 (26.9) 10 (24.4) 15 (6.7) 5 (12.2) p= 0.045 21 (9.4) 5 (12.2) 164 (73.5) 32 (78) 12 (5.4) 0 9 (4.0) 3 (7.3) 2 (0.9) 1 (2.4) 12.8 +/-12.56 17.6 +/-15.0 p=0.05 54 (24.2) 12 (29.3) p= 0.57 14 (6.3) 3 (7.3) p=0.47 118 (52.9) 19 (46.3) 50 (22.4) 8 (19.5) 48 (21.5) 14 (34.1) 6 (2.7) 0 1 (0.45) 0 FIGO IRM stage (2009) 0.13 IA 5 (8.2) 4 (12.5) 0.48 IB 49 (80.3) 25 (78.1) 0.79 < 2 cm ≥2 cm -<4cm ≥4 cm NA 23 19 1 6 11 10 0 4 IIA 6 (9.8) 0 / IIB 1 (1.6) 3 (9.4) 0.11 Tumor size (mm) 15.8 16.4 0.6 LVSI 18 (29.5) 10 (31.3) 1 Preoperative brachytherapy 5 (8.2) 3 (9.4) NA Adjuvant therapy 0.75 None 27 (44.3) 17 (53.1) 0.5 Brachytherapy 25 (41) 9 (28.1) 0.26 RT-CHT 14 (23) 10 (31.2) 0.59 Robot asssited surgery 13 (12.7) -NA Laparoconversion -4 NA J o u r n a l P r e -p r o o f

*RT-CHT: radiation therapy and chemotherapy

Table 3 :

 3 Surgical parameters

		MIS	Open	p-value
		n= 61	n=32
	Mean length of surgery (min)	228	278	0.17
	Intraoperative complications	6 (8.3)	5 (15.6)	0.5
	 Urinary	2 (3.3)	3 (9.4)
	-Bladder injury	1	1
	-Ureteral injury with	1	2
	reimplantation
	 Vascular	1 (6.6)	0
	 Digestive	1 (6.6)	1 (3.1)
	 Other	2 (3.3)	1 (3.1)
	Postoperative complications	12 (19.7)	9 (28.1)	0.43
	 Dysuria/Urinary retention	5	1
	 Uretero-vaginal fistula	0	1
	 Lymphocele	1	1
	 Pelvic abscesses/peritonitis	1	1
	 Hemorrhagic complication	0	1
	 Autres  Reoperation (among previous	7 2	7 5
	complication)
	Mean length of hospital stay (days)	5.9	9.0	< 0.01

Table 4 :

 4 Histopathologic characteristics

		MIS	Open	p-value
		n= 61	N=32
	Negative margins	54 (88.5)	27 (84.4)	0.74
	Length of the vaginal cuff (mm)	14.05	14.50	0.88
	Parametrial invasion	6 (8.3)	5 (15.6)	0.5
	Vaginal invasion	4 (6.6)	2 (6.3)	1
	Lymph nodes invasion	6 (8.3)	5 (15.6)	0.5