Primerjava onkološkega izhoda kirurškega zdravljenja zgodnjega stadija raka endometrija glede na vrsto kirurškega pristopa (laparoskopski, laparotomijski) Laparoscopy versus laparotomy for the management of early-stage endometrial cancer: Effect on oncological outcomes

Background and aim : Endometrial cancer is the most common gynecologic malignancy diagnosed in an early stage in 80% of patients. The standard tre-atment for this includes hysterectomy, bilateral salpingo-oophorectomy

In approximately 80% of cases, the histological image showed endometrial adenocarcinoma. In up to 20% of cases, however, rarer forms develop: papillary, serous, clear cell, mucinous, carcinosarcoma, or mixed carcinoma. These had a poorer prognosis and a greater probability of distant metastases. The treatment of FIGO stage I endometrial cancer is primarily surgical and includes total hysterectomy with bilateral adnexectomy. In the past, the surgical  (2). Traditionally, the surgical procedure was carried out through laparotomy. Laparoscopic surgery is a more modern approach, while robotic surgery has also become increasingly common. Compared with laparotomy, the laparoscopic approach is safer, mainly in overweight women, as it has a lower risk of postoperative wound infection, less blood loss, and less bowel obstruction (ileus) (3). In the case of laparoscopy, the duration of hospitalization is shorter, recovery is faster, and treatment is cheaper (4). Studies indicate that laparoscopy and laparotomy are comparable in terms of long-term disease management (5,6). However, when laparoscopy was introduced for the treatment of endometrial cancer, the main concern was that metastatic tumors or lymph nodes that were difficult to reach, which could otherwise be sensed by touch in laparotomy, would be overlooked due to the loss of tactile sensitivity. Moreover, the potential change in the pattern of recurrence due to the high intraabdominal pressure caused by CO2 or a potential tumor spillage due to the use of an intrauterine manipulator was also a cause of concern. The world of scientific research was shocked in 2018 with the results of the LACC (Laparoscopic Approach to Cervical Cancer) prospective randomized study comparing the oncological outcome of patients with operable early-stage cervical cancer who were treated laparoscopically/robotically or with laparotomy (7). For safety reasons, this study ended early, and it clearly showed a significantly poorer oncological outcome for patients treated laparoscopically/robotically. This was not, however, expected considering the data from retrospective analyses. No explanation could clarify the mechanism behind the higher recurrence rate when using laparoscopy, but the laparoscopic/ robotic treatment of cervical cancer was abandoned nonetheless.    Table 3 shows the features of the patients in both groups with disease recurrence. In the laparotomy group, six patients developed recurrence, of which two had metastases in distant organs (one of them underwent postoperative radiation) and four had local recurrence (one of them underwent postoperative radiation). Four of the six patients had the endometrioid subtype of endometrial carcinoma, G1/G2; the basic condition of one patient was endometrioid subtype, poorly differentiated (G3); and one had carcinosarcoma. In the laparoscopy group, two patients had recurrence, one with local recurrence and one with distant metastases; neither of them underwent adjuvant radiotherapy. Both had the endometrioid subtype of endometrial carcinoma, G1/G2.

DISCUSSION
This study confirmed that the recurrence rate and diseasefree survival of FIGO stage I endometrial cancer did not significantly differ between patients who underwent surgical treatment using laparotomy and those who underwent the laparoscopic procedure. The recurrence rate of endometrial cancer is generally about 13% and only up to 3% in patients with low risk disease (9). Recurrence in terms of anatomical location is evenly distributed between local recurrence and distant metastases. Most frequently, the disease recurs in the vaginal vault, the lesser pelvis, abdominal cavity, or in the lungs. The prognostic factors affecting the recurrence rate are histological type, tumor grade, depth of myometrial invasion, LVI, tumor size, growth into the bottom segment of the uterus, positive peritoneal cytology, presence of metastases in the lymph nodes, age of the patient, and specific molecular markers (1,8,10). Survival is also affected by comorbidities, American Society of Anesthesiologists score, and postoperative complications within 30 days following surgical treatment (9). The disease-free 5-year survival for patients without metastases in the lymph nodes is estimated to be 90%. Therefore, we found that the recurrence percentage at our center was comparable with the published data as expected, for both the laparoscopy and laparotomy groups (11).
The laparoscopic approach has numerous advantages, including a lower risk of serious postoperative complications, such as infection and the dehiscence of the postoperative wound, major blood loss, and bowel obstruction (ileus). Also, the postoperative recovery is significantly faster, the duration of hospitalization is shorter; the reported quality of life is significantly higher up to 6 months after the procedure, and, finally, the treatment cost is lower. Both approaches are comparable in terms of the frequency of major intraoperative complications. For this reason, it was a logical step in the past to ensure that the laparoscopic approach also spread to oncological surgery, especially in the event of localized diseases. Therefore, the introduction of the laparoscopic approach to treating endometrial cancer also began at the Department of Gynecologic and Breast Oncology, University Medical Center Maribor in 2008. Whenever a new approach becomes available in oncological surgery, it must be evaluated in terms of safety and its impact on the oncological outcome. For this reason, we performed the first clinical study in our center to find the impact of the new approach on the oncological outcome after 5 years of primary treatment. As expected, this study confirmed that the laparoscopic approach had a longer duration of surgery, which was consistent with the findings of previous studies; however, in clinical terms it outweighed the benefits of laparoscopy (5,12). We also confirmed that one of the quality indicators for the oncological surgery of endometrial cancer, that is, the number of removed pelvic lymph nodes, did not differ depending on the approach. As already stated, we also could not confirm any differences in the recurrence rate and disease-free survival.
A meta-analysis of randomized studies looking into the advantages of laparoscopic treatment of early-stage (specifically FIGO stage I to IIA) endometrial cancer was recently conducted (in 2018). The metaanalysis data proved the safety of laparoscopy in longterm disease management, as the recurrence rate in patients who were monitored for an average of 38-59 months after laparoscopic treatment was 7.9%-12.6%, while the recurrence rate in patients after treatment with laparotomy was 8.1%-11.5% (3). The pattern of recurrence in terms of local or distant recurrence was, just like in this study, evenly divided between the laparoscopy group and the laparotomy group (3). The largest randomized study called LAP2, which included 2616 patients with FIGO stage I-IIA endometrial cancer, showed that the cumulative recurrence rate 3 years after the procedure was 11.4% in the laparoscopy group and 10.2% in the laparotomy group (1.14% difference) (13). However, the study did not meet the specific criteria for assessing the noninferiority of the laparoscopic method, perhaps mainly due to the expected low recurrence rate. The overall survival compared between the groups was practically identical (89.8%). The study also included patients with a nonendometrioid tumor. Although the authors highlighted that the power of the study was not sufficient to assess whether the surgical method was suitable for these patients, they also did not note any differences in the recurrence rate between the laparoscopy and laparotomy groups. The recurrence rate at the site of the trocar after laparoscopic surgery was extremely low (0.24%). The study also emphasized the better reported quality of life of patients after laparoscopic surgery (13). Then, another larger retrospective study analyzed patients who received surgical treatment for FIGO stage II endometrial cancer, where the tumor had spread to the cervix. The study included 2175 patients and confirmed the best short-term perioperative outcome for patients and even an improved 3-year overall survival of patients after a minimally invasive surgical procedure (14). This study had multiple shortcomings. First, the retrospective approach of the study made the gravity of the results lesser. However, we still found that this constituted a significant data overview, as the active monitoring and publishing of oncological outcomes is the most important quality indicator of every oncological center. The groups were also poorly comparable due to this retrospective approach and the selection. We wished to counteract this as much as possible by including all ACTA MEDICO-BIOTECHNICA 2023; 16 (1): 29-37 consecutive patients as well as patients for whom the standard procedure had been fully carried out (total hysterectomy, adnexectomy, and lymphadenectomy). The groups of patients did not differ depending on the recurrence risk, which was the most important fact that could be related to survival differences. However, the groups did differ in the percentage of patients who received postoperative radiation. This could be related to the impact on recurrence. However, we must be aware that the indications for postoperative radiation have changed over the years, mainly toward radiation being performed less frequently than in the past. The reason for the decrease in indications for radiation was that no evidence showed the relation of radiation to any benefits for the oncological outcome. This was also confirmed by our results, as the group with a lower level of postoperative radiation did not have more recurrences. The groups also differed in the percentage of patients with positive peritoneal washing cytology, but mostly because we failed to obtain test results for the majority (90.4%) of the laparotomy group, while the higher percentage in the laparoscopy group was the result of more frequently performed hysteroscopy prior to surgical treatment (15). In theory, the laparoscopic approach (with the use of an intrauterine manipulator) could be correlated with an increased frequency of LVI and a higher recurrence rate; however, studies have not shown this to be the case (16,17). We wished to verify this in our study, but we could not reach any conclusions because of the lack of relevant data. The data concerning LVI only became significant and required histological parameters for early endometrial cancer with the latest guidelines for treating endometrial cancer published in 2020 (8); previously, it had not been routinely prescribed in regular clinical practice. The biggest statistical problem, not just of our analysis but also of other studies, when studying the oncological outcomes of patients with FIGO stage I endometrial cancer, is the excellent prognosis and long-term survival, which means that a very high number of participating patients and a very long period of observation are necessary for the statistical and clinical values of the analysis. For endometrial cancer, this should optimally be at least 10 years.

CONCLUSIONS
This study and the studies published thus far have indicated a comparable oncological outcome of the surgical treatment of early-stage endometrial cancer in addition to all the advantages of the laparoscopic approach compared with laparotomy. Therefore, the laparoscopic approach has been classified in the latest ESGO guidelines as a recommended approach for all patients with early-stage endometrial cancer. Furthermore, constant monitoring and research are recommended, as the low frequency of recurrence and long disease-free survival make it more difficult to determine the effects on the oncological outcomes.

DISCLOSURE
The authors declare no conflicts of interest.