{"paper_id":"2a131258-114f-4ec3-aa99-4e2c03c49ae6","body_text":"Endometrial cancer (EC) is a cancer that occurs in women. [ 1 ][ 2 ]. According to the\nstatistics published in the past decades, the prevalence of EC in the world is\nincreasing. Accordingly, in 2020, about 4.5% of women’s cancers are EC. Also,\nEC-related deaths in the world are reported to be 97,000 [ 3 ]. Despite the expansion of knowledge and progress in the\ntreatment of patients, the death rate of patients is still high [ 4 ][ 5 ].\nWhen the diagnosis of EC in patients is delayed and the disease is detected in\nadvanced stages, the survival rate of patients decreases significantly. Metastasis\nis an important issue that health workers are facing today in connection with EC\npatients. During EC progression, malignant cells metastasize to various organs. One\nof the most important organs is actually the ovary. Ovarian involvement (OI) has\nbeen observed in many EC patients. Despite infertility in the patient, this conflict\nalso reduces their survival [ 6 ][ 7 ][ \n8 ][ 9 ][ 10 ].\nRecently, it has been shown that there are many risk factors related to EC metastasis\nin patients. Each of these risk factors, based on their nature, has a different\neffect on EC metastasis in ovarian metastasis [ \n11 ][ 12 ][ 13 ]. These risk factors are acquired and inherited. Some study\nconducted asses risk factors in EC, But the important point is that the risk factors\nare different in each region based on the conditions of the patients [ 14 ][ 15 ][ 16 ].\nUnderstanding the risk factors associated with OI is clinically significant for\npreserving fertility and other complications and improving prognosis. This issue\nimpacts treatment decisions, outcomes, prognosis, and patient management. Some\nstudies have been conducted to investigate this matter. However, many risk factors\nrelated to OI have not been identified. The current research focuses on assessing\nthe risk factors associated with OI in patients with EC.\n\nStudy Design\nThis retrospective study was conducted to determine the risk factors of OI following\nEC in female patients with a definitive diagnosis of uterine cancer admitted to Imam\nKhomeini Hospital in Tehran over the preceding 15 years, between 2010 and 2024. The\ndiagnosis of EC in patients was confirmed based on the results of tests and also\nbased on pathology results. This was while the patients were checked under the\nsupervision of the relevant specialist.\nInclusion and Exclusion Criteria\nIn this study, 280 female patients diagnosed with uterine cancer (including\nendometrial and non-endometrial adenocarcinoma) were included for analysis. Patient\ndata were extracted from the hospital’s archival records. Patients with a history of\npre-existing ovarian diseases, infertility, prior use of hormonal medications such\nas oral contraceptive pills (OCPs), or pelvic infections preceding uterine cancer\ndiagnosis were excluded.\nData Collection\nThrough a retrospective review of hospital records, comprehensive patient data were\ncollected encompassing demographic features (age, gravidity, parity) and\nlesion-specific details (pathological grading, uterine cancer subtypes, myometrial\ninvasion, cervical, lymph node, non-endometrioid histology, and vascular lymphatic\nspace invasion). Patients were stratified into two groups based on evidence from\nimaging reports and biopsy findings: those with OI involvement and those without.\nSubsequently, these two groups’ baseline parameters were compared to discern factors\nassociated with OI development.\nEthical Considerations\nPatients' private information remained utterly confidential. Their diagnostic and\ntreatment paths were not disturbed, and no extra cost was imposed on the patient.\nAny exploitation of patients' information was done with their permission and the\napproval of the center's research assistant (IR.TUMS.IKHC.REC.1402.299).\nMethod for Calculating Sample Size\nBased on the study by Ashrafganjoei et al. [ 17 ],\nwhich reported a prevalence of OI at 1.11%, and considering a confidence level of\n95% and a precision level of 5%, the minimum required sample size for the study was\ndetermined to be equivalent to 152 cases.\nN=P ˟ (1 - P) ˟ Z1-α/2 2/d2\nP=0.111, α=0.05, Z1-α/2= 1.96, d=0.05\nN=152\nStatistical Analysis\nThe results were reported as mean ± standard deviation (mean ± SD) for quantitative\nvariables and percentages for categorical variables. The data distribution was not\nnormal, so the Mann-Whitney test was used. Mann-Whitney was applied to compare\nquantitative variables, while chi-square test was used for qualitative variables.\nMultiple logistic regression analysis was conducted to identify risk factors related\nto OI. A significance level of 0.05 or lower was considered statistically\nsignificant. Statistical analysis was carried out using SPSS version 23 software\n(IBM Corp., Armonk, NY., USA).\n\n• As P<0.05\n• As P<0.05\n• As P<0.05\nIn this study, the 280 data of female patients diagnosed with uterine cancer\n(including endometrial and other types of sarcoma) were extracted from the\nhospital's archival files\nand analyzed.\nDemographical Information of Patients\nData analysis showed that there was no\nsignificant relationship between age, gravid and parity between the two groups (P>0.05).\nHowever,\nit was found that the difference in the frequency of grades I, II and III in the two\ngroups was\nstatistically significant (P=0.008). Also, in relation to the type of pathology,\nthere were three\ntypes of endometrioid, serous, clear cell, and carcinoma sarcoma, and the difference\nin frequency\nbetween the two groups was statistically significant (P<0.001, Table- 1 ).\nPathological Information of Patients\nThe results showed that the frequency of Myometer,\nLVSI, cervix, serous, tube, intra-abdominal, lymph node and omentum was different\nbetween the two\ngroups, so these differences were statistical significant (P<0.05). Based on\nthis, it was found\nthat their frequency was higher in the group without OI. Also, in terms of\ncomplaints, which were\ndivided into different categories, a comparison was made between the two groups,\nwhich was\nstatistical statistically (P<0.001, Table- \n2 ).\nUnivariate and Multiple Analysis of Risk Factors\nIn univariable analysis, deep (>50%)\nmyometrial invasion (OR=2.06, 95% CI: 1.04_3.9, P=0.96), non-deep (<50%)\nmyometrial invasion\n(OR=0.3, 95% CI: 0.13_0.65, P=0.23), omentum involvement (OR=21.36, 95% CI:\n5.50_82.94, P=0.03),\nP.P.C (OR=10.96, 95% CI=3.38_35.46, P=0.015), full myometrial invasion (OR=5.2, 95%\nCI=1.51_17.99,\nP=0.28), cervical stromal involvement (OR=2.14, 95% CI=1.04_4.40, P=0.75),\nparametrial invasion\n(OR=2.7, 95% CI=1.06_7.22, P=0.36), uterine serosa extension (OR=5.6, 95%\nCI=2.16_14.60, P=0.63),\nfallopian tube involvement (OR=6.14, 95% CI= 2.53_14.90, P=0.48), lymph node\ninvolvement (OR=2.71,\n95% CI=1.10_6.68, P=0.77), and serous carcinoma (OR=5.6, 95% CI=2.36_13.60, P=0.006)\nshowed\nsignificant differences (Table- 3 ).\nROC Curve Analysis\nIn Figure- 1 , ROC curve analysis\nwas analyzed for the diagnostic value of demographic variables in patients. Based on\nthis, the\nresults showed that only the variable and grade was significant (P=0.013). It was\nalso determined\nthe sensitivity and specificity for age (sensitivity: 62.26%, specificity: 50%),\ngravid\n(sensitivity: 81.32%, specificity: 57.14%), parity (sensitivity: 47.08%,\nspecificity: 60.71%), and\ngrade (sensitivity: 74.32%, Specificity: 53.57%) was calculated.\nIn Figure- 2 , ROC curve analysis was analyzed for\nthe\ndiagnostic value of pathology variables in patients. The results showed that all\nfour variables of\ncervix, serous, tube and intra-abdominal were significant (P<0.05). Also,\nsensitivity and\nspecificity for cervix (sensitivity: 81.32%, specificity: 57.14%), serous\n(sensitivity: 93.77%,\nspecificity: 50%), tube (sensitivity: 93.77%, specificity: 43.46%), and\nintra-abdominal\n(sensitivity: 96 .89%, Specificity: 28.57%) was calculated.\n\nFigure  1 . Roc curve analysis related\ndemographic variables. A: parity, B: Age, C: grade and D: gravid.\nFigure  2 . Roc curve analysis related\npathological variables. A: cervix, B: serous, C: tube, and D:\ninta-abdominal.\nThe main objective of present study was to identify the factors that cause OI in EC\nand mitigate\nthis complication by addressing modifiable factors. Identifying these risk factors\nis critical\nto developing effective treatment strategies and improving patient management. The\nresults\nshowed that the frequency of Myometer, LVSI, cervix, serous, tube, intra-abdominal,\nlymph node\nand omentum was different between the two groups, so these differences were\nstatistical\nsignificant (P<0.05).\nBased on this, it was found that their frequency was higher in the group without OI.\nAlso, in\nterms of complaints, which were divided into different categories, a comparison was\nmade between\nthe two groups, which was statistical statistically (P<0.001). In univariable\nanalysis, deep\n(>50%) myometrial invasion, non-deep (<50%) myometrial invasion, omentum\ninvolvement,\nP.P.C, full myometrial invasion, cervical stromal involvement, parametrial invasion,\nuterine\nserosa extension, fallopian tube involvement, lymph node involvement, and serous\ncarcinoma\nshowed significant differences In addition, our study confirms that myometrial\ninvasion is a\nsignificant factor associated with OI. Both deep (>50%) and non-deep (≤50%)\nmyometrial\ninvasion were significantly associated with outcome, with deep invasion representing\na higher\nrisk. This is consistent with previous clinical studies demonstrating an association\nbetween\ndeep myometrial invasion and OI in patients with EC [ 18 ][ 19 ][ 20 ] [ 14 ][ 21 ][ 22 ],.\nHigh histologic grade (G2-G3) and lymphatic space\ninvasion (LVSI) were also identified as valuable indicators for assessing OM,\nconsistent with\nour findings and previous studies [ 23 ][ 24 ].\nThis finding is consistent with a 2022 study that identified age as a variable\ninfluencing OI in\nEC patients [ 25 ]. It is essential to consider\nage-related\ndifferences when developing treatment strategies for EC patients. In a similar study\nconducted\nby Matoba et al., they reported that in the analysis, pathological findings\nindicating that\nLymphatic space invasion (LSI), cervical stromal involvement (CSI) peritoneal\ndissemination, and\novarian swelling (OvS) were cause progression of disease. Additionally, type 2\nhistologic type,\nLSI, CSI, and OvS were significantly more common in cases with OM in stage I and II\nwithout\nadnexal pathological factors. In multivariate analysis, LSI, CSI, and OvS emerged as\nsignificant\nrisk factors for OI [ 23 ].\nType II EC cancer (e.g., serous or clear cell carcinoma) is more likely to\nmetastasize to the\novaries compared to Type I (endometrioid) EC [ \n23 ][ 26 ]. In a 2023 study of 1240\npatients with EC, Qian Li and\nXin Zhang concluded that deep myometrial invasion, lymph node metastasis, and higher\nCA125\nlevels may be independent high-risk factors for OI in patients with EC. OI has a\nhigher\ninfluence on the prognosis in patients with low-risk EC [ \n27 ]. OI in EC patients significantly impacts prognosis. It is associated\nwith poorer\noutcomes and lower overall survival rates. The presence of OI often necessitates\nmore aggressive\ntreatment strategies and can affect decisions regarding fertility preservation\n[ 20 ][ \n27 ][ 28 ].\nOne large multicenter retrospective study conducted by Ignatov et al. [ 20 ] in 2329 patients with EC, the 5-year overall\nsurvival rate was\nsignificantly lower in patients with OI (51.9%) than those without (84.6%). They\nfound that OI\nin EC patients is associated with poorer prognosis and reduced survival rates\ncompared to those\nwithout OI [ 20 ]. EC is still the most common\ncancer of\nthe female reproductive system and is responsible for around 20% of deaths worldwide\n[ 29 ]. The high invasiveness and metastatic\ncapacity of this\ncancer, especially to the ovaries, requires comprehensive treatment strategies,\nincluding\nprimary hysterectomy, bilateral salpingo-oophorectomy, and pelvic and para-aortic\nlymphadenectomy.\nThis standard treatment protocol is critical even for young patients with low-risk,\nearly-stage\nEC, where oophorectomy is performed as part of the surgery to reduce the risk of\nmetastasis.\nDespite the solid findings, this study faced some issues, including a limited number\nof eligible\npatients and a retrospective case-control design. Inconsistent pathology reports of\nprecursor\nlesions such as endometrial hyperplasia or concurrent ovarian endometriosis could\nhave\ninfluenced the final diagnosis. Therefore, future research should focus on\ndeveloping novel\ngenetic tools to accurately classify patients with complex symptoms and strive for a\nmore\naccurate research database.\n\nOverall, this study underscores the significant risk factors for OI in EC, which\ninclude deep and\nnon-deep myometrial invasion, omentum involvement, ascites, full stromal cervical\ninvolvement,\nparametrial invasion, uterine serosa extension, fallopian tube involvement, lymph\nnode\ninvolvement, and serous carcinoma. P.P.C, omentum involvement, and serous carcinoma\nare powerful\npredictors.\nIdentifying these risk factors is crucial for developing effective treatment\nstrategies,\nespecially for preserving fertility in young women. Future research should focus on\nlarger,\nprospective studies and the development of genetic tools to enhance diagnostic\nprecision and\ntreatment outcomes.\n\nWe wish thank you of all our colleague in Isfahan university of medical science.\n\nThe authors declare that they have no conflict of interest.","source_license":"CC-BY-4.0","license_restricted":false}