Challenges and Controversies in the Surgical Treatment of Cervical Cancer: Open Radical Hysterectomy versus Minimally Invasive Radical Hysterectomy

Objective: The aim of the study was to perform a systematic assessment of disease-free survival (DFS), overall survival, and morbidity rates after open radical hysterectomy (ORH) and minimally invasive surgery (MIS) for early-stage cervical cancer and discuss with experts the consequences of the LACC trial (published by Ramirez et al. in 2018) on clinical routine. Methods: A total of 5428 records were retrieved. After exclusion based on text screening, four records were identified for inclusion. Five experts from three independent large-volume medical centers in Europe were interviewed for their interpretation of the LACC trial. Results: The LACC trial showed a significantly higher risk of disease progression with MIS compared to ORH (HR 3.74, 95% CI 1.63 to 8.58). This was not seen in one epidemiological study and was contradicted by one prospective cohort study reported by Greggi et al. A systematic review by Zhang et al. mentioned a similar DFS for robot-assisted radical hysterectomy (RRH) and LRH. Recurrence rates were significantly higher with MIS compared to ORH in the LACC trial (HR 4.26, 95% CI 1.44 to 12.60). In contrast, four studies presented by Greggi reported no significant difference in recurrence rates between LRH/RRH and ORH, which concurred with the systematic reviews of Zhang and Zhao. The experts mentioned various limitations of the LACC trial and stated that clinicians were obliged to provide patients with detailed information and ensure a shared decision-making process. Conclusions: The surgical treatment of early-stage cervical cancer remains a debated issue. More randomized controlled trials (RCT) will be needed to establish the most suitable treatment for this condition.


Introduction
In 2018, Ramirez  Study design: systematic reviews (SRs), meta-analyses, literature reviews, and randomized controlled trials (RCTs) Titles and abstracts identified through the electronic database and web searches and, subsequently, full paper copies of all potentially eligible reports were screened independently by two reviewers; any disagreements were resolved by discussion. No restrictions were placed on language or publication status.
In order to compare the existing (non-randomized) evidence with the LACC trial conducted by Ramirez et al., newer reviews covering comparable outcomes were selected.

Searches
To avoid missing any relevant SRs and RCTs, a focused literature search was conducted using a combination of free text and database thesaurus terms. No restrictions on language or publication status were applied. Reference lists of the included articles were also searched for additional studies.

Data Extraction
Data were extracted by one reviewer and checked by a second. Any discrepancies were resolved by discussion or the intervention of a third reviewer.

Reviewing Expert Opinions from Large-Volume Centers
Oncologists from three independent medical centers in Europe servicing large numbers of patients and adhering to a certified mode of quality control were interviewed. The questionnaire addressed their experience after the results of the LACC trial. All experts were confronted with the data of the literature research performed in this study. These findings have been included in the discussion. Detailed answers can be found in Appendix A.

Quality (Risk of Bias) Assessment
The risk of bias (methodological quality) of RCTs was assessed using the Cochrane Risk of Bias Tool for randomized clinical trials, while reviews were assessed using ROBIS [16,17].
Risk of bias assessment was performed by one reviewer and checked by a second reviewer. Any discrepancies were resolved by the intervention of a third.

Data Synthesis
Results of the LACC trial and relevant reviews were reported as a narrative synthesis with tables and figures.

Literature Searches and Inclusion Assessment
A total of 5428 records were retrieved from the database searches. After de-duplication, 3996 records remained. These articles were screened on the basis of titles and abstracts; 13 were ordered for full-text screening and eight were excluded. After the full-text screening stage, three records were identified for inclusion in the review.
The flow of studies through the search and screening processes is summarized in Figure 1.

Overview of Included References
This review included four recent publications (Table 3), including one RCT, the Laparoscopic Approach to Cervical Cancer (LACC) trial, published in November 2018 [1, 18,19]. Greggi et al. [20] was a recent narrative review, while Zhao and Zhang were both SRs [21,22].
The primary studies included in the reviews are listed in Table A1 (see Appendix A). A similar number of primary studies were included in each review, i.e., Zhao 2017 (n = 23), Zhang 2019 (n = 25), and Greggi (n = 24).
A total of 63 primary studies were incorporated in the three reviews. None of these studies were included in all three secondary publications, while nine primary studies featured in two of the secondary publications. The reasons for these were the eligibility criteria and the methodology of the reviews.

Overview of Included References
This review included four recent publications (Table 1), including one RCT, the Laparoscopic Approach to Cervical Cancer (LACC) trial, published in November 2018 [1, 18,19]. Greggi et al. [20] was a recent narrative review, while Zhao and Zhang were both SRs [21,22]. The primary studies included in the reviews are listed in Table A1 (see Appendix A). A similar number of primary studies were included in each review, i.e., Zhao 2017 (n = 23), Zhang 2019 (n = 25), and Greggi (n = 24).
A total of 63 primary studies were incorporated in the three reviews. None of these studies were included in all three secondary publications, while nine primary studies featured in two of the secondary publications. The reasons for these were the eligibility criteria and the methodology of the reviews.

Methods of LACC Trial
The LACC trial was an international, open-label, multicenter phase III RCT evaluating the hypothesis that minimally invasive (laparoscopic or robot-assisted) radical hysterectomy was not inferior to ORH. The trial was conducted at 33 centers across the world and recruited patients between June 2008 and June 2017.
The primary outcome was DFS or death from cervical cancer. Secondary outcomes were locoregional recurrence (pelvic or distal), progression-free survival, treatment-related morbidity (intraoperative complications, time to discharge, perioperative complications, early postoperative wound and vault complications within 4 weeks, long-term morbidity to 6 months, estimated blood loss, postoperative pain, and analgesic consumption), OS, quality of life, pelvic floor distress inventory, feasibility of sentinel lymph node biopsy, and costs.

Results of the LACC Trial
The trial was terminated prematurely in June 2017 by the data and safety monitoring committee due to concerns about an imbalance in deaths between the two groups. A total of 631 patients had been randomized until this time: 319 to minimally invasive and 312 to ORH. In the minimally invasive group, 269 (84.4%) underwent laparoscopy and 50 (15.6%) underwent robot-assisted surgery.
The estimated rates of DFS at 4.5 years were 86.0% for MIS and 96.5% for ORH (difference −10.6%, 95% confidence interval (CI) −16.4 to −4.7%). There was no evidence of the non-inferiority of minimally invasive surgery to ORH, as the 95% CI included the non-inferiority margin of −7.2%. DFS following MIS was significantly poorer than with ORH ( Table 2). Adverse events of the LACC trial were reported by Obermair et al., including the incidence of intra and postoperative adverse events within six months after surgery [23]. This analysis included 536 (85%) of the 631 randomized patients, of whom 279 (52%) underwent MIS and 247 (48%) ORH. Only those who had undergone surgery and been followed up for at least six months were included in the analysis, which was based on the treatment received (Table 3).  Table 4 compares outcomes, DFS (disease-free survival), overall survival (OS), and recurrence rates, in the LACC trial and the three secondary publications. The LACC trial revealed a significantly higher risk of disease progression or death with MIS compared to ORH (HR 3.74, 95% CI 1.63 to 8.58). However, the increase was not seen in two meta-analyses and one epidemiological study reported in the review by Greggi et al., which yielded no significant difference between laparoscopic radical hysterectomy (LRH) and ORH. One prospective cohort study contradicted the LACC and reported a DFS of up to 5 years with MIS compared to ORH (92.8 vs. 81.3%, p = 0.03) [20]. The SR performed by Zhang et al. included seven observational studies reporting either the estimated percentage with DFS or the disease-free interval. Although no meta-analysis was performed, the authors registered similar DFS rates for RRH and LRH, and a slightly higher DFS rate for RRH compared to ORH [22].

Overview of the Results
The numbers of patients with recurrent disease were also significantly higher after MIS compared to ORH in the LACC trial (HR 4.26, 95% CI 1.44 to 12.60). In contrast, the four studies reviewed by Greggi et al. that reported recurrence rates yielded no significant difference between RRH or LRH and ORH [20]. The SRs performed by Zhang and Zhao also did not reveal any significant difference in recurrence rates between the various types of surgery [21,22].
As regards overall survival, the LACC trial showed a significantly higher risk of death due to any cause after MIS compared to ORH (93.8 vs. 99.0%; HR 6.00, 95% CI 2.77 to 20.3) [1]. Greggi et al. mentioned one prospective study that reported significantly better survival rates after MIS compared to ORH (91 vs. 78.9%, p = 0.026), and one epidemiological study that reported a significantly lower survival rate after LRH compared to ORH (90.9 vs. 94.7%, p = 0.002) [20]. The two other secondary publications reporting on overall survival did not mention a statistically significant difference between LRH and ORH (Table 4).
Zhao noted significantly fewer pelvic lymph nodes retrieved with LRH compared with ORH (mean difference (MD) 1.65, 95% CI 3.19 to 0.11), but Zhang found no significant difference between RRH and ORH.
The estimated blood loss was significantly lower for MIS compared to ORH in the LACC trial [1]. Similar data were noted by Zhao and Zhang in their SRs [21,22]. Accordingly, fewer patients with MIS required a blood transfusion compared to those who underwent ORH in the LACC trial as well as in the SRs by Zhao and Zhang [1, 21,22]. The systematic review by Zhao reported significantly fewer patients with adverse events such as ileus or vaginal fistulas after LRH compared to ORH, while the LACC trial reported no significant difference between groups (Table 5).

Risk of Bias
Overall, the risk of bias was rated low for the LACC trial [16]. Some minor issues were noted, such as blinding and reporting of the safety population.
The publication by Greggi et al. was a narrative review and hence did not follow a predefined protocol or inclusion criteria. This publication has been assigned an unclear overall risk of bias for each domain [20]. The risk of bias was rated high for the SRs performed by Zhang and Zhao.
The main limitation of both SRs was that they were based on observational studies, with the exception of one small Chinese RCT included in Zhao's review [21,22,25,26]. Many of the meta-analyses reviewed by Zhang and Zhao had high levels of statistical heterogeneity, which may have been due to the fact that they pooled a variety of prospective and retrospective study designs [21,22]. Neither of the reviews included a sensitivity or subgroup analysis, particularly by study design, to explore this heterogeneity. A summary is shown in Figure 2, while detailed assessments of the three secondary publications are reported in Supplementary Table S1.

Discussion
The data of the three reviews highlight the discrepancy between the LACC trial and the expectations of gynecologists throughout the world, namely the fact that MIS may worsen the outcome.
This discrepancy characterizes the still ongoing dilemma faced by experts. The minimally invasive approach had become the more favored technique because of its fewer side effects and estimated equivalent oncological outcome compared to other procedures for the treatment of early-stage cervical cancer [8][9][10].
The outcomes presented in the LACC trial, i.e., DFS, OS, recurrence rates, and adverse events, were extracted for all reviews. Zhang et al. reported RRH as a unique intervention, while Zhao and Greggi et al. summarized RRH and LRH as MIS [20][21][22]. In contrast to the main endpoint of the LACC trial, the three reviews did not report a significantly lower DFS after MIS compared to ORH [20][21][22]. Observational studies mentioned by Zhang et al. even described a higher DFS with RRH compared to ORH [20][21][22].
The same was noted for the secondary endpoints of OS and recurrence rates; neither of these differed significantly between MIS and ORH in all three reviews [20][21][22].
In the LACC trial, MIS was associated with shorter hospital stays, less blood loss, and less blood transfusion but higher intra and postoperative complication rates. The reviews of Zhao and Zhang et al. provided a more detailed account of these aspects. Zhao reported significantly fewer pelvic lymph nodes retrieved with LRH compared with ORH, but Zhang found no significant difference between RRH and ORH.
These findings corroborate the personal experience of the experts we addressed from University Hospital Center of Porto, Portugal, Hannover Medical School, and University Hospital Kiel, Germany, who failed to confirm a significant difference in DFS and the risk of death between ORH and LRH at their medical centers.
The main objection to the LACC trial was its short duration of follow-up, which may have concealed a higher recurrence rate in the ORH group [10]. Furthermore, the proficiency of surgeons in performing MIS is debatable because the surgeons needed to have conducted only ten operations in order to participate in the trial. Additionally, the participation rate of countries in which MIS is a highly established method was low [9,10]. The expert at the Hannover medical school stated that "some critics question the operative expertise of the respective centers, especially with reference to the learning curve of laparoscopic radical hysterectomy, which became established as a routine procedure worldwide only a few years before the start of the study".
One of the main points of criticism about the LACC trial is the heterogeneous use and missing evaluation of the uterine manipulator. This point was addressed in earlier studies. Breakage of the uterine manipulator in the pelvis or shortly after surgery is responsible for many cases of recurrence, which was probably also true of the LACC trial

Discussion
The data of the three reviews highlight the discrepancy between the LACC trial and the expectations of gynecologists throughout the world, namely the fact that MIS may worsen the outcome.
This discrepancy characterizes the still ongoing dilemma faced by experts. The minimally invasive approach had become the more favored technique because of its fewer side effects and estimated equivalent oncological outcome compared to other procedures for the treatment of early-stage cervical cancer [8][9][10].
The outcomes presented in the LACC trial, i.e., DFS, OS, recurrence rates, and adverse events, were extracted for all reviews. Zhang et al. reported RRH as a unique intervention, while Zhao and Greggi et al. summarized RRH and LRH as MIS [20][21][22]. In contrast to the main endpoint of the LACC trial, the three reviews did not report a significantly lower DFS after MIS compared to ORH [20][21][22]. Observational studies mentioned by Zhang et al. even described a higher DFS with RRH compared to ORH [20][21][22].
The same was noted for the secondary endpoints of OS and recurrence rates; neither of these differed significantly between MIS and ORH in all three reviews [20][21][22].
In the LACC trial, MIS was associated with shorter hospital stays, less blood loss, and less blood transfusion but higher intra and postoperative complication rates. The reviews of Zhao and Zhang et al. provided a more detailed account of these aspects. Zhao reported significantly fewer pelvic lymph nodes retrieved with LRH compared with ORH, but Zhang found no significant difference between RRH and ORH.
These findings corroborate the personal experience of the experts we addressed from University Hospital Center of Porto, Portugal, Hannover Medical School, and University Hospital Kiel, Germany, who failed to confirm a significant difference in DFS and the risk of death between ORH and LRH at their medical centers.
The main objection to the LACC trial was its short duration of follow-up, which may have concealed a higher recurrence rate in the ORH group [10]. Furthermore, the proficiency of surgeons in performing MIS is debatable because the surgeons needed to have conducted only ten operations in order to participate in the trial. Additionally, the participation rate of countries in which MIS is a highly established method was low [9,10]. The expert at the Hannover medical school stated that "some critics question the operative expertise of the respective centers, especially with reference to the learning curve of laparoscopic radical hysterectomy, which became established as a routine procedure worldwide only a few years before the start of the study".
One of the main points of criticism about the LACC trial is the heterogeneous use and missing evaluation of the uterine manipulator. This point was addressed in earlier studies. Breakage of the uterine manipulator in the pelvis or shortly after surgery is responsible for many cases of recurrence, which was probably also true of the LACC trial [10,26,27]. Chiva et al. performed a large retrospective multicenter trial in Europe and evaluated the role of the uterine manipulator: patients who underwent MIS with a uterine manipulator had a 2.76-fold higher risk of recurrence compared to those treated by the open approach. Patients treated with MIS without the uterine manipulator had similar rates of relapse as those who underwent ORH [28]. The experts agreed that "the use of the uterine manipulator might be one of the main reasons for the poorer outcomes after minimally invasive surgery". However, from the primary studies included in the three reviews, we were unable to determine the influence of the surgical technique.
Since the LACC trial had no unique preoperative technique for tumors <2 cm separately, the influence of tumor size on survival and recurrence rates remains a debated issue. Several groups have tried to evaluate the outcome for tumors <2 cm, but the data permit no unequivocal statement. In general, MIS appears to be as safe as ORH in this subgroup [28][29][30].
The interviewed gynecological experts emphasized the importance of sufficient lymph node dissection independent of the surgical technique. Zhao et al. reported significantly fewer pelvic lymph nodes retrieved with LRH compared with ORH, but Zhang et al. found no significant difference between RRH and ORH [21,22]. The limited body of data concerning a potential difference in prognosis between minimally invasive surgery and laparotomy based on the number of extracted lymph nodes also calls for further investigation.
According to the experts, pelvic lymph node dissection via MIS is effective when performed at highly qualified centers by skilled and well-trained surgeons. The most widely accepted explanation is that surgery by laparoscopy or robotics provides the surgeon with a better view of anatomical structures and surgical landmarks, which could be beneficial for the excision of lymphatic tissue. However, experts at the University of Kiel stated that "local recurrences within the lower pelvis, specifically in the area of the internal iliac artery" appear to be more frequent in minimally invasive surgery.
The existing published literature does not permit surgeons to adopt a specific procedure as the gold standard for the treatment of early-stage cervical cancer. However, none of the experts we interviewed were aware of a significantly higher recurrence rate with MIS compared to ORH.
The LACC trial, as an RCT, offers the highest level of evidence in the existing literature on the treatment of early-stage cervical cancer. The bias potential of non-randomized studies must be considered when comparing the existing data with the LACC trial.
The experts were unanimous as regards their obligation to inform patients about the results of the LACC trial [8]. In addition to the critical points of the LACC trial, patients should be informed about studies reporting contrary results, such as those of Chiva and Köhler et al., who mention an equivalent outcome for MIS without the use of a uterine manipulator and with the use of combined vaginal-assisted laparoscopic radical hysterectomy (VALRH) for protective vaginal closure [28,31]. The surgical approach should be selected on the basis of a shared decision-making process.
However, it should be noted that current studies reporting expert opinions on the issue are not concurrent with regard to the surgeon's individual long-term experience. Not all questions raised by the LACC trial have been resolved. Well-designed and -structured studies will be needed in the near future in order to offer patients accurate advice for the treatment of early-stage cervical cancer [32].

•
Although the LACC trail is a multicenter randomized trial it has some caveats lowering the power of its results. But since it is Level Ib evidence one should be cautious not considering these results when discussing the surgical procedure with the patient. To me the results of LACC overweigh the results from mostly retrospective observational studies.
Which consequences do the results of the LACC trial have on your daily practice?
• Patients need to be informed about the results of LACC during the informed consent procedure prior to treatment. Having said that, I would perform robotic assisted minimal invasive surgery in cases such as ≤FIGO Ia2, no evidence of lymphvascular invasion and no adenocarcinoma differentiation. Furthermore, we do have to inform the patient that radio-therapy is a valid option curing patients from low stage cervical cancer.
From your experience with the treatment of cervical cancer could you see any difference between minimally invasive surgery vs. open radical hysterectomy according to the recurrence rate?

•
To me local recurrences within the lower pelvis, explicitly in the area of the internal iliac artery seems higher to me in minimal invasive surgery.
Do you agree that Cervical cancer cells stimulated by a CO 2 pneumoperitoneum environment have an increased the ability to proliferate after a short period of inhibition?
• I doubt that CO 2 plays a role in cell proliferation. However, I can imagine that the increased intra-abdominal pressure could potentially affect the tumor cell that way that residual cells are pushed into niches.
Do you evaluate these facts as critical weakness for the inclusion criteria at the LACC trial?

•
The facts are weakening the LACC results but overall the results seem to be reliable. Do you agree, that the results of the LACC trial, as a single multicenter randomized controlled trial, should overweigh the body of evidence from mostly retrospective observational studies.

•
The LACC trial outcomes should be taken into account critically and meticulously compared with other scientific validated studies that several oncological referral centres have already published. It may have a problematic premise and surgeon bias. The LACC trial seems to have methodology limitations, and the inclusion criteria are questionable (pe. surgeon proficiency criteria for minimally invasive surgery in the trial were only 10 cases and a total of 2 un-edited videos; the participation of countries where minimally invasive surgery has become the treatment of choice was low, and the LACC trial did not report the operational technique, etc.). The surgical related morbidity and mortality may be worse in the laparotomy arm. There is missing data in the LACC trial like surgical cohorts well balanced for all demographic variables, all tumours variables, stage, the overall number of lymph nodes removed, number of positive lymph nodes, post-treatment receipt of adjuvant radiation and chemotherapy, . . .
Which consequences do the results of the LACC trial have on your daily practice?
• After the LACC trial, we developed a new informed consent form in the department. The patients should be clearly informed and allowed to choose. If patients consent, we offer a minimally invasive surgical approach in cases of squamous cell carcinoma in stage IB1 cervical cancer with tumour size ≤ 2 cm. We've implemented routine vaginal closure before colpotomy (vaginal cuff from below, by laparoscopy using a linear stapler).
While new and reliable data comes in, the option has been more towards an open radical hysterectomy approach.
From your experience with the treatment of cervical cancer comparing minimally invasive surgery (laparoscopic radical hysterectomy and/or robotic radical hysterectomy) vs. open radical hysterectomy could you report any differences of intra-operative and post-operative complications?

•
Our data and covering intra-operative complications do not report any significant difference between radical laparoscopic hysterectomy and open radical hysterectomy. Concerning postoperative complications, they have been more common in the open radical hysterectomy group (namely urinary retention, sexual and bowel dysfunction). Probably, because by laparoscopic/robotics approach, it is possible to identify better the anatomy, and a nerve-sparing approach is more feasible. Seeing better, we also can treat better. The pneumodissection offered by laparoscopy/robotics facilitates the access of the retroperitoneal space, where the lymphatic nodes are located.
Do you share the critique points, and do you believe that the pelvic lymph nodes dissection with minimal invasive surgery is technically more complicated?
• With a well-trained team and following the standard steps, MIS enhances the pelvic lymph node dissection. The surgeon has a better anatomical vision by laparoscopy or robotics and can be more efficient in the lymphatic tissue excision respecting anatomical and surgical landmarks. The precision offered by laparoscopy/robotics allows a more precise approach, sparing the nerves, the small vessels and even, in some cases, the lymphatics (eventually causing less lymphedema/lymphocysts). In my opinion, the LACC study has the following points of criticism: 1.
Based on the reported funding of $121.250 from Medtronic in the original publication, it must be doubted that sufficient funding for management, data collection and quality assurance with appropriate validation of the many parameters was possible.

2.
The main point of criticism, in my opinion, is the failure to observational studies from the last two years, can have a significant influence on tumour cell dissemination and thus on the locoregional recurrence rate in laparoscopic radical hysterectomy. In particular, the use of the uterine manipulator and abdominal colpotomy are associated with an increased risk. The formation of a vaginal cuff over the portio is another protective maneuver.

3.
The brief follow-up observation of the study can in principle be viewed as a point of criticism. It was shown that in the study evaluation in 2019, i.e., one year after the publication in the NEJM the HR decreased from 6.0 to 2.9. However, the differences are still clearly significant! 4.
Some critics question the operative expertise of the respective centres, especially with reference to the learning curve of laparoscopic radical hysterectomy, which became established as a routine procedure worldwide only a few years before the start of the study.
In summary, I would like to refer to the statement by the AGE and AGE, published with me as first author in GebFra, and I still fully agree with the statement even 18 months after this publication.
Do you agree, that the result of the LACC trial, as a single multicentre randomized controlled trial, should overweigh the body of evidence from mostly retrospective observational studies?
• I am convinced that the validity of the only larger randomized multicentre study to date is very high and with regard to its evidence, outweighs the retrospective observational studies. The results of the retrospective observational studies are, however, generating hypotheses, so that, in my opinion, further larger multicentre randomized studies should urgently be initiated. • During the last ten years, we didn't notice any difference between the two approaches in University Hospital Kiel, although we didn't collect out data. In University Hospital Aachen, Germany in the early 2000s we noticed a difference. But at that time, we could not define the reason for the worse outcome after the minimally invasive surgery.
Do you agree, that the result of the LACC trial, as a single multicentre randomized controlled trial, should overweigh the body of evidence from mostly retrospective observational studies.

•
The LACC trial by Ramirez et al. was a very well performed and well-structured study. The medical centres taking part had a high standard. We have to take the results seriously although smaller, mostly retrospective studies, inferior to the LACC trial, showed different results. In my opinion, every medical centre must keep an eye on their own outcome data.
Do you think, that the inconsistent use of the uterine manipulator and applied technic as well as the unequal experience of the surgeons of the partaking medical centres of the LACC trial had an influence of the results?
• I don't think, that the different experience of the involved surgeons had an outstanding impact on the results of the LACC trial. The effect on the outcome was remarkable even with well trained and very experienced surgeons. The usage of the uterine manipulator might be one of the main reasons for the worse outcome data after minimally invasive surgery. One could easily imagine that tumour cells might migrate into the pelvis once the tumour is broken by the manipulator. Data from Köhler et al. support that concept.
Do you see CO 2 pneumoperitoneum as a reason for the worse outcome after MIC?
• Trocar metastasis as well as CO 2 must be considered as possible reasons for the worse outcome data after MIC.
Which consequences do the results of the LASS trial have for your daily practice?
• After the publication of the LACC trial one must inform the patient very well about the existing data and based on that, one should perform a shared decision making considering the advantages and disadvantages of both approaches. • The critical factor with the level of the experience of the surgeons remain underestimated in the literature, one of the drawbacks of the LACC trial is the absence of a unique parameter for the inclusion of the surgeons and difficulty to reach a unique evaluation of the quality of the surgery performed. Moreover, the different number of dissected pelvic lymph nodes with in the surgery shows the need for a universal definition, however the risks profile and the cofactors are different from one case to the other. The role presented by the Co2 demands a detailed investigation in the near future, however it increases the propensity for cervical cancer to implant. The uterine manipulator plays a role for increasing the recurrence rate at the vaginal vault, probably through invasion of the vaginal mucosa, resulting in the spread and spillage of the tumour cells.
• Since the publication of the results of the LACC study, we perform a detailed consultation of the patients showing the results published by the LACC study and the discrepancy to our individual results. The decision for the surgery is based on shared decision making with the help of decision panels which shows the different literature and experience. I emphasise the unknown role of the manipulator and the fact that also non vaginal vault pelvic recurrences occurred in the minimally invasive surgery group. The importance to have a standard uniform adequate staging examination of the patients before planning the entire treatment in order to avoid the discrepancy and the heterogenicity by risk of recurrence, which is one of the drawbacks of the LACC study, with variation and sometimes lack of presurgical assessment of the staging examination. The need for a more detailed decisions aid presented by the oncology society would results in a more confidence at the process of decision making and avoid any sort of prevalence by the centres, which emphasize the need to organize more training sessions to improve and retrain the training skills of the medical personals to perform those sophisticated consultation.