Impact of proper surgical treatment on the survival of patients with epithelial ovary cancer

ABSTRACT Objective: to evaluate the quality of surgical treatment of ovarian cancer patients and assess the impact of adequate surgical oncological treatment on disease-free survival and overall survival of patients with advanced epithelial ovarian cancer. Methods: this is an observational, retrospective study with quantitative analysis, with the collection of data in medical records of a temporal convenience sample of patients diagnosed with ovarian cancer admitted to a High Complexity Oncology Unit, in Belo Horizonte, from the period of 2014 to 2020. Results: a total of 91 patients diagnosed with ovarian cancer were evaluated, with the epithelial histopathological type being the most frequent (85%). Of this total, 68 patients (74.7%) had advanced-stage ovarian cancer. Appropriate surgical treatment was performed in 30.9% of patients with advanced epithelial ovarian cancer and the type of performed surgery was statistically significant for overall survival. This low proportion of appropriate surgical oncological treatment was not related to surgical specially or surgeon competence, but mainly to advanced disease related to patient flow at UNACON. It was not possible to confirm if the advanced-stage disease was related to tumor biology or losing time from diagnosis to oncological surgery. Conclusion: overall survival of advanced-stage epithelial ovarian cancer patients is directly influenced by appropriate surgical treatment, however, in this study, the percentage of advanced ovarian cancer receiving adequate surgical treatment was much lower than the rates reported in the literature. To improve these outcomes, we believe that surgeons should keep following patients during neoadjuvant chemotherapy to point to a better time for surgery, and clinical oncologists should better consider adequate oncological surgery as one of the pillars of ovarian cancer treatment and get more involved in facilitating surgeries.


INTRODUCTION
E pithelial ovarian cancer is the most prevalent histopathological type (85 to 90%) among malignant ovarian tumors 1,2 . It is considered the leading cause of death among gynecological cancers and the fifth leading cause of cancer death in women. It is more prevalent in the sixth and seventh decade of life, with more than 70% of patients being diagnosed in advanced stages of the disease, leading to an average survival in 5 years, which ranges from 30.3% to 44.1% and less than a 40% chance of cure. In 2018, in the United States, it was estimated that 22,240 new diagnostic cases and 14,070 deaths were due to this pathology 2-5 . In clinical practice, patients with epithelial ovarian cancer are divided into two large groups according to the staging system of the International

A B S T R A C T A B S T R A C T
Objective: to evaluate the quality of surgical treatment of ovarian cancer patients and assess the impact of adequate surgical oncological treatment on disease-free survival and overall survival of patients with advanced epithelial ovarian cancer. Methods: this is an observational, retrospective study with quantitative analysis, with the collection of data in medical records of a temporal convenience sample of patients diagnosed with ovarian cancer admitted to a High Complexity Oncology Unit, in Belo Horizonte, from the period of 2014 to 2020. Results: a total of 91 patients diagnosed with ovarian cancer were evaluated, with the epithelial histopathological type being the most frequent (85%). Of this total, 68 patients (74.7%) had advanced-stage ovarian cancer. Appropriate surgical treatment was performed in 30.9% of patients with advanced epithelial ovarian cancer and the type of performed surgery was statistically significant for overall survival. This low proportion of appropriate surgical oncological treatment was not related to surgical specially or surgeon competence, but mainly to advanced disease related to patient flow at UNACON. It was not possible to confirm if the advanced-stage disease was related to tumor biology or losing time from diagnosis to oncological surgery. Conclusion: overall survival of advanced-stage epithelial ovarian cancer patients is directly influenced by appropriate surgical treatment, however, in this study, the percentage of advanced ovarian cancer receiving adequate surgical treatment was much lower than the rates reported in the literature.
To improve these outcomes, we believe that surgeons should keep following patients during neoadjuvant chemotherapy to point to a better time for surgery, and clinical oncologists should better consider adequate oncological surgery as one of the pillars of ovarian cancer treatment and get more involved in facilitating surgeries. Cytoreductive surgery is indicated, as initial treatment, in patients with advanced-stage ovarian cancer. The main objective is total resection (complete debulking) or almost total resection when macroscopic residual lesions smaller than 1cm in their largest diameters persist intra-abdominally (optimal debulking).
Complete and/or optimal debulking rates of up to 70% to 80% have been reported in several reference centers in the treatment of ovarian cancer, however, over 50% rates are considered acceptable in the literature [7][8][9][10][11] .
In cases of patients with high-risk complications for a major surgical procedure or whose Literature data show that the extent of debulking is correlated with disease-free survival and overall survival 15,16 . However, patients with very extensive carcinomatosis and a large volume of disease in the upper abdomen and/or mesenteric involvement tend to obtain lower benefits when undergoing complete and/ or optimal debulking procedures 17,18 .

MATERIALS AND METHODS
This is an observational, retrospective study of quantitative analysis data collection through the analysis of medical records. There was no interference in surgical procedure choice, but we were interested in The key objective was to evaluate the quality of surgical treatment mainly concerning its oncological radicality including the types of surgical treatments performed, and their respective percentage were evaluated. The types of surgeries performed were grouped into the following groups: complete cytoreductive surgery (debulking); optimal cytoreductive surgery (debulking); cytoreductive surgery (debulking) suboptimal; and biopsy surgery. The first two were considered adequate and the last two were considered palliative.
Subsequently, patients were stratified into two groups to assess the impact of adequate surgery on these patients' survival. The "Backward Method" used was the complete model with successive discarding of the variables that, adjusted concerning the others, did not present a significance level of <0.05. In the evaluated model, no variable was associated, therefore, the initial model was maintained.
In all tests, the significance level adopted was 5%, therefore, comparisons whose p-value was less than or equal to 5% were considered significant. The software used for the analysis was SPSS version 23.0.    (Figure 1).   Figure 2).

Impact of proper surgical treatment on the survival of patients with epithelial ovary cancer
There was no significant difference in overall survival stratified by performance status (PS), surgical risk, degree of differentiation, and surgeon specialty (Figures 4-6).
No combined factors were found to be associated with overall survival in the Cox multivariate model ( Table 6).     The median disease-free survival of patients with advanced-stage ovarian epithelial tumor (FIGO stage IIB-IV) was 9.9 ± 3.2 months, (95% CI: 3.7 -16.1).

DISCUSSION
When evaluating the type of primary surgical treatment performed in patients with advanced-stage ovarian cancer, we observed as shown in Table 3 that only five out of a total of 68 patients (7.35%) underwent an oncological surgical treatment considered adequate up-front, showing a large discrepancy about literature data that consider acceptable rates of around 50%. In Faria Impact of proper surgical treatment on the survival of patients with epithelial ovary cancer reference centers for the treatment of ovarian cancer, these rates can reach levels of 70 to 80% 7-11 .
One hypothesis that could be raised to justify these data would be the fact that our patients are being referred to neoadjuvant treatment because they have very extensive disease, during primary surgery, which would make it impossible to perform a complete or optimal cytoreductive surgery. This hypothesis can be supported as from 68 patients, 55 were stage IIIC and seven were stage IVB (91.2%), which means a very extensive disease that could have led the surgical team to decide on neoadjuvant chemotherapy and further interval surgical treatment 7-13 . Those differences were not related to surgical specialty or the competence of the surgical team but mainly to tumor patients staging presenting for surgery with advanced disease when is not feasible to perform standard patterns of oncological procedures. However, when analyzing the institution in totality, the total number of patients diagnosed with advanced-stage ovarian cancer who underwent surgical oncological treatment considered adequate, whether performed primarily or after chemotherapy, was only 30.9%, which is, much lower than the rates reported in the literature for reference centers for the treatment of ovarian cancer [7][8][9][10][11] .
To analyze the impact of surgical treatment on the prognosis of the studied patients and facilitate comparison with the literature, we selected only patients with advanced-stage ovarian cancer, whose histopathological classification was of the epithelial type.
In this group of patients, we found a median overall survival of 28. 3