{"paper_id":"b90b9efb-b673-4daa-93b8-810f50fb4c7d","body_text":"1Rev Bras Ginecol Obstet. 2025;47:e-rbgo59.\nOriginal article\nAbstract\nObjective: This study aims to to evaluate the frequency of ovarian involvement in endometrial cancer \npatients aged 50 years and younger, identify associated clinicopathological factors, and uniquely \nassess the role of the Systemic Immune-Inflammatory Index (SII) in predicting ovarian involvement.\nMethods: Patients aged 50 years and younger diagnosed with endometrial cancer between 1992 \nand 2022 were retrospectively analyzed. Two groups were formed based on adnexal involvement: \nthose with (ovarian metastasis or synchronous ovarian cancer) and without adnexal involvement. \nClinicopathological predictors of adnexal involvement were evaluated. Preoperative complete \nblood count values (platelet, leukocyte, lymphocyte, and neutrophil counts) were used to calculate \ninflammatory indices: PLR (platelet-to-lymphocyte ratio), NLR (neutrophil-to-lymphocyte ratio), \nand SII (neutrophil × platelet / lymphocyte). A two-group analysis was performed based on the cut-\noff values of statistically significant parameters. Univariate and multivariate logistic regression \nanalyses were conducted.\nResults: Among 205 patients, histopathological ovarian metastasis was identified in 5.9% (n=12), \nand synchronous ovarian tumors in 2.4% (n=5). Significant differences were observed in neutrophil \ncounts, NLR, and SII values between the groups (p<0.05). ROC analysis showed the optimal SII cut-\noff value as 992.58, with 70% sensitivity and 76% specificity (AUC=0.726). Ovarian involvement was \nsignificantly more frequent in patients with SII ≥ 992 (p<0.05). Univariate analysis revealed that \nmyometrial invasion, LVSI, cervical stromal invasion, lymph node metastasis, omental involvement, \ngrade of tumor, NLR and SII were significantly associated with ovarian involvement (p<0.05). \nMultivariate analysis identified histological grade, myometrial invasion, pelvic lymph node \nmetastasis and SII as independent risk factors (p<0.05).\nConclusion: Ovarian involvement is uncommon in patients under 50 years of age with low-grade \ntumors, absence of myometrial invasion, negative pelvic lymph nodes, and preoperative SII < 992.58. \nOvarian-sparing surgery may be a safe option in selected cases, and SII could serve as a valuable \nindex in guiding ovarian preservation decisions.\nHow to cite\nŞahin B, Gürbüz TB, Duru Çöteli SA, \nBegen EE, Akay A, Boran N, et al. A novel \nmarker in the ovarian preservation \napproach to endometrial cancer: \nsystemic immune inflammatory \nindex. Rev Bras Ginecol Obstet. \n2025;47:e-rbgo59. \nDOI\nhttp://dx.doi.org/10.61622/rbgo/2025rbgo59\nA novel marker  in the ovarian preservation approach to \nendometrial cancer: systemic immune inflammatory index\nBüşra Şahin 1 \n https:/ /orcid.org/0000-0003-2420-6233\nTansu Bahar Gürbüz2 \n https:/ /orcid.org/0000-0002-8315-1044\nAyşe Sinem Duru Çöteli 3  \n https:/ /orcid.org/0000-0002-6558-7549\nEmel Ebru Begen1 \n https:/ /orcid.org/0000-0003-0770-3334\nArife AKAY1 \n https:/ /orcid.org/0000-0001-9640-2714\nNurettin Boran3 \n https:/ /orcid.org/0000-0002-0367-5551\nYaprak Üstün1\n https:/ /orcid.org/0000-0002-1011-3848\n1Department of Obstetrics and Gynecology, Ankara Etlik Zübeyde Hanım Women’s Health Training and Research Hospital, Ankara, Turkey. \n2Department of Obstetrics and Gynecology, Duzce Ataturk State Hospital, Duzce, Turkey\n3Department of Gynecological Oncology, Ankara Health Science University Etlik Zubeyde Hanim Women’s Health and Research Hospital, Ankara, Turkey.\nConflicts to interest: none to declare. \nKeywords \nEndometrial neoplasms; Ovarian \nneoplasms; Leukocytes; Neutrophils; Blood \nplatelets; Organ preservation;  Systemic \nimmune inflammatory index\nSubmitted \nJanuary 13, 2025\nAccepted \nMay 6, 2025\nCorresponding author \nBüşra Şahin \nE-mail: drbusrasahin1@gmail.com \nAssociate Editor\nSophie Françoise Mauricette \nDerchain  \n(https://orcid.org/0000-0003-1029-9993) \nUniversidade Estadual de Campinas, \nCampinas, SP , Brazil\n\n2\nA novel marker  in the ovarian preservation approach to endometrial cancer: systemic immune inflammatory index\nŞahin B, Gürbüz TB, Duru Çöteli SA, Begen EE, Akay A, Boran N, et al. \nRev Bras Ginecol Obstet. 2025;47:e-rbgo59.\nIntroduction\nEndometrial cancer (EC) is the most common gynecologic \nmalignancy worldwide with an age-standardized prevalence \nof 8.4% following cervical cancer. In Turkey, it is the most com-\nmon gynecologic malignancy with a prevalence of 6.1% in all \nage groups and 3.8% in women aged 25-49 years.(1,2)\nFive percent of the patients are diagnosed before \nage 40, and the incidence of early age EC is increasing. (3-5) \nIncidence of adnexal metastases in EC ranges from 2% to \n8.1% and are usually characterized by ovarian pathologies \nthat can be detected during surgery.(6-9) According to the lit-\nerature, microscopic metastasis is less than 1% in patients \nwith adnexal involvement. Synchronous ovarian cancer is \nseen in 2% of the patients, and these patients usually have \nabnormal ovarian morphology. (10-13)\nSurgical staging is done in EC, and hysterectomy with \nbilateral salpingo-oophorectomy (BSO) is the standard \ntreatment due to the risk of microinvasive ovarian involve-\nment. In the early period, due to estrogen deficiency, vaso-\nmotor symptoms, sexual dysfunction, sleep disorders, and \nmood changes may be observed in patients undergoing \nBSO. In the long term, patients are at an increased risk for \nosteoporosis and cardiovascular diseases.(14-19)\nThese problems, which are secondary to oophorec-\ntomy, brought the ovarian preservation approach into \nquestion for the young patient group. When studies in the \nliterature are examined, there is no clear consensus on the \nsubject, especially due to the risk of micrometastasis to the \novary. However, one of the most recent reviews concluded \nthat an ovarian-sparing approach can be applied to patients \nwith FIGO stage 1A, grade 1-2, endometrioid type, and those \nyounger than 40 years. (20) Disease confined to the pelvis, \ndisease microscopically limited to the uterus and ovary, \nand low histologic grade are good prognostic factors for \nsynchronous ovarian cancer. In addition, deep myometri -\nal invasion on preoperative imaging, high ca125 levels and \npositive adnexal involvement on MRI/ 3urgical exploration \nare among the independent predictive factors for coesting \nadnexal malignancy.(9,10)\nSII is considered a good index of local immune re-\nsponse and systemic inflammation based on peripheral \nlymphocyte, neutrophil and platelet counts. In recent years, \nthere has been increasing interest in the tumor microenvi -\nronment.  Inflammatory changes in the tumor microenviron-\nment are known to have an impact on cancer cell prolifera -\ntion, metastasis, angiogenesis, and immune escape.(21,22)\nSII has an important role in survival and prognosis in \ngynecologic malignancies.  In a recent study, high SII was \npresented as an independent risk factor for postmenopaus-\nal advanced EC. (23) On the other hand, ovarian involvement \nis known to be important in EC prognosis. However, there is \nno study in the literature investigating the relationship be-\ntween ovarian involvement and SII. Therefore, knowing the \nadnexal participation incidence and synchronous ovarian \ncancer in endometrial cancer patients and defining the pa -\nrameters to predict the adnexal participation will guide the \ndecision for an ovarian preservation approach. \nThis study aims to determine the frequency of ovarian \ninvolvement in patients aged 50 years and younger, investi-\ngate the associated factors, and, unlike other studies in the \nliterature, investigate the role of the systemic immune-in-\nflammatory index (SII) in ovarian involvement.\nMethods\nAll the patients diagnosed with endometrial cancer who \nreceived primary surgical treatment at the Gynecological \nOncology Clinic of the Health Sciences University Etlik \nZübeyde Hanım Gynecology and Obstetrics Training and \nResearch Hospital between 1992 and 2022 were retrospec-\ntively scanned using the hospital’s information system. \nPatients aged 50 and under were included in the study, and \ntheir demographic characteristics and pathology reports \nwere reviewed. Patients were examined in two groups: pa -\ntients with adnexal involvement (ovarian metastasis and \nsynchronous ovarian cancer) and patients without adnexal \ninvolvement. Information on histological type (endometri -\noid, non-endometrioid), histological grade (grade 1, grade \n2-3), FIGO (International Federation of Gynecology and \nObstetrics, 2009) stage (stage 1-2, stage 3-4), myometrial \ninvasion (no MI, <50% MI, >50% MI), lymphovascular inva -\nsion (LVSI), endocervical glandular involvement, cervical \nstromal involvement, lymph node metastasis, omental in-\nvolvement, and cytology were recorded. Clinicopathological \nparameters that can be used to predict the adnexal partici -\npation were analyzed in both groups.\nComplete blood count parameters (platelet, leukocyte, \nlymphocyte, neutrophil) obtained from the preoperative pa-\ntients were analyzed using the Mindray BC-6000 device. To \nevaluate inflammatory indices, PLR (platelet/lymphocyte), \nNLR (neutrophil/lymphocyte), and SII (neutrophil x platelet/\nlymphocyte) were calculated, and the values   were recorded \nin the patient’s follow-up form. A two-group analysis was \nperformed between the groups by determining the cut-off  \nvalue for the statistically significant parameters. For the lab-\noratory parameters, cut-off values were determined for the \nvariables that were significant using a ROC analysis. A two-\ngroup analysis was also performed. Independent predictive \nfactors were investigated by performing a multivariate lo-\ngistic regression analysis for parameters that were signifi -\ncant in the univariate analysis between both groups.\nAnalyzes were done with the SPSS 21.0 program and \nwere studied at a confidence level of 95%. The kurtosis \nand skewness values obtained from the measurements \nbetween +3 and -3 were sufficient for the normal distribu -\ntion. Numbers (n) and percentages (%) were calculated for \n\n3\nA novel marker  in the ovarian preservation approach to endometrial cancer: systemic immune inflammatory index\nŞahin B, Gürbüz TB, Duru Çöteli SA, Begen EE, Akay A, Boran N, et al. \nRev Bras Ginecol Obstet. 2025;47:e-rbgo59.\ncategorical variables and mean standard deviation (SD) \nwas calculated for numerical variables. Statistical signifi -\ncance was taken as p<0.05. Parametric variables were ana -\nlyzed with a T-test or Mann Whitney U Test according to the \nnormal distribution for the two independent groups. The \nrelationship between categorical variables was analyzed \nwith the Chi-square test. Moreover, the results of multivar -\niate analysis and ORs of logistic regression analysis struc-\ntures between groups for categorical variables were also \npresented. Predictive factors were analysed with a multi -\nvariate logistic regression analysis. The receiver operating \ncharacteristic (ROC) curve was used to show the sensitivity \nand specificity of SII and NLR. The detection value of β-hCG \nincreases to 1 when the area under the curve (AUC) value is \ngreater than 0.5. Also, the appropriate equation was created \nusing regression analysis for SII and NLR.\nFor this retrospective study, permission numbered \n2024/11 was received from the Local Ethics Committee of the \nHealth Sciences University Etlik Zübeyde Hanım Gynecology \nand Pediatrics Training and Research Hospital 30.10.2024.\nResults\nA total of 205 patients were included in the study, and his-\ntopathological ovarian metastasis was detected in 5.9% \n(n=12), and synchronous ovarian tumor was detected in \n2.4% (n=5). The median age of the patients was 44.6±4.7 \nyears. No statistically significant difference was found in \novarian involvement between those under and over 45 (p: \n0.917). Clinicopathological features of the patients with \nand without ovarian involvement are presented in table 1. \nIn the univariate analysis, non-endometrioid histological \ntype, increased grade, advanced stage disease, myometrial \ninvasion depth, LVSI, cervical stromal invasion, lymph node \nmetastasis, and omental involvement indicate an increased \nrisk for ovarian involvement (p<0.05).  Preoperative hemato-\nlogic parameters are shown in Table 2. A statistically signif-\nicant difference was found in neutrophil count (p = 0.015), \nNLR (p = 0.020), and SII (p = 0.023) between the two groups. \nMean SII was significantly higher in the group with adnexal \nmalignancy (1201.62 ± 631.95 vs. 808.54 ± 586.96).\nROC analysis results are summarized in table 3. The \narea under the curve (AUC) was 0.751 for NEU, 0.738 for NLR, \nand 0.726 for SII, indicating good diagnostic performance. \nThe optimal cut-off values were: NEU ≥ 5.02 (80% sensitiv-\nity, 64.5% specificity), NLR ≥ 2.63 (80% sensitivity, 64.5% \nspecificity), and SII ≥ 992.58 (70% sensitivity, 76% specific-\nity). When patients were grouped according to the SII cut-\noff value of 992.58, adnexal malignancy was found to be \nsignificantly more frequent in those with higher SII values \n(p < 0.05).\nThe histopathological features and intraoperative find-\nings of patients with ovarian involvement are evaluated in \nTable 1. Comparison of clinicopathologic risk factors between pa -\ntients with and without coexisting adnexal malignancies\nVariables\nNo \ncoexisting \nmalignancy\nGroup 1\nn=188\nCoexisting \nmalignancy\nGroup 2\nn=17\np-value\nn(%) n(%)\nAge\n   ≤ 45 86(91.5) 8(8.5) 0.917\n   46-50 102(91.9) 9(8.1)\nHistologic subtype\n   Endometrioid 163(94.2) 10(5.8) 0.002\n   Non-endometrioid 25(78.1) 7(21.9)\nHistologic grade\n   Grade 1 150(96.2) 6(3.8) <0.001\n   Grade 2-3 38(77.6) 11(22.4)\nStage\n   1-2 172(98.3) 3(1.7) <0.001\n   3-4 16(53.3) 14(46.7)\nMyometrial invasion\n  No 67(97.1) 2(2.9) <0.001\n  Yes 121(88.9) 15(11.1)\nLVSI\n   No 167(94.9) 9(5.1) <0.001\n   Yes 21(72.4) 8(27.6)\nEndocervical glandular involvement\n   No 180(90.1) 16(8.2) 0.754\n   Yes 8(88.9) 1(11.1)\nCervical stromal invasion\n   No 177(94.1) 11(5.6) <0.001\n   Yes 11(64.7) 6(35.3)\nMetastases to pelvic lymph nodes\n   No 175(95.6) 8(4.4) <0.001\n   Yes 13(59.1) 9(40.9)\nMetastases to para-aortic lymph nodes\n   No 181(93.8) 12(6.2) <0.001\n   Yes 7(58.1) 5(41.7)\nOmental involvement\n  No 186(93) 14(7) <0.001\n  Yes 2(40) 3(60)\nLVSI - Lymphovascular Space Invasion; Chi-Square; Fisher’s Exact Test\nTable 2. Comparison of inflammatory markers between patients \nwith and without coexisting adnexal malignancies\nNo coexisting \nmalignancy\nGroup 1\nn:121\nCoexisting \nmalignancy\nGroup 2\nn:10\np-value\nPlatelets (x103/mm3) 309.52±102.92 330.18±101.66 0.436**\n Leukocytes (x103/mm3) 7.65± 2.49 9.04± 2.34 0.051*\nLymphocytes (x103/mm3) 2.06± 0.68 1.99±1.06 0.369*\nNeutrophils (x103/mm3) 4.85± 2.08 6.19±1.59 0.015*\nNLR (%) 2.55± 1.26 3.59±1.34 0.020**\nPLR (%) 163.55± 70.38 203.09± 115.53 0.054**\nSII 808.54± 586.96 1201.62± 631.95 0.023*\nNRL - Neutrophil Lymphocyte Ratio; PLR - Platelet Lymphocyte Ratio; SII - Systemic Inflammatory Index   \n* t-test; **Mann Whitney test\ntable 4. While normal ovarian morphology was observed in \n6 patients, extrauterine spread was present in 83% of the \npatients with normal ovarian morphology. Only in one pa -\ntient older than 45 years of age, despite normal ovarian mor-\nphology, no intraoperative spread outside the uterus was \n\n4\nA novel marker  in the ovarian preservation approach to endometrial cancer: systemic immune inflammatory index\nŞahin B, Gürbüz TB, Duru Çöteli SA, Begen EE, Akay A, Boran N, et al. \nRev Bras Ginecol Obstet. 2025;47:e-rbgo59.\ndetected. There were patients younger than 45 years of age, \nhaving advanced disease in the presence of micrometastat-\nic ovaries, indicating extrauterine spread. Intraoperative \novarian morphology was abnormal in all the cases with \nsynchronous ovarian cancer (Table 4). Univariate analysis \nrevealed that myometrial invasion, LVSI, cervical stromal in-\nvasion, lymph node metastasis, omental involvement, grade \nof tumor, NLR and SII were significantly associated with \novarian involvement (p<0.05) (Table 5).\nIn the multivariate logistic regression analysis (Table \n5), myometrial invasion (OR: 12.4; 95% CI: 1.49–45.92; \np=0.046), pelvic lymph node metastasis (OR: 30.54; 95%CI: \n1.96–475.72; p=0.015), tumor grade (OR: 19.7; 95%CI: 1.17–\n350.6; p=0.042), and high SII (≥992.58) (OR: 1.45; 95%CI: \n1.01–12.34; p=0.034) remained as independent predictors of \nadnexal involvement.\nDiscussion\nOne of the most critical problems in the management of \nthe premenopausal patient group of EC patients is the early \nand late consequences of surgical menopause secondary \nto bilateral salpingo-oophorectomy included in the stan-\ndard treatment. The ovarian preservation approach for these \npatients is one of the controversial issues due to ovarian \nmicrometastasis. Therefore, it is crucial to investigate the \nincidence of ovarian involvement in EC patients, to identify \nthe risk factors for ovarian participation, and to determine \nthe parameters to be used in selecting suitable patients for \novarian-sparing surgery.\nThe most recent study on the subject reported that \novarian metastasis occurred at incidences ranging from \n2% to 8.1% for the patients who underwent oophorectomy \ndue to endometrial cancer. (20) Moreover, studies that only \nincluded patients diagnosed with EC under the age of 50 \nshow that ovarian metastases were detected at incidences \nranging from 1-8%, and synchronous ovarian cancer is de-\ntected at 3-5%. (3,8)\nIn this study, it is found that ovarian metastasis was \nseen in 5.9% of the patients and synchronous ovarian involve-\nment was seen in 2.4% of the patients, and these findings \nare consistent with the literature. Six of the patients had mi-\ncrometastatic ovarian involvement, and extrauterine metas-\ntasis was observed in 83% of the patients in whom micromet-\nastatic ovaries were detected. Micrometastatic ovaries were \ndetected in only one patient over 45 years of age, although the \novaries were normal, and there was no extrauterine spread. \nThe micrometastatic ovarian involvement rate in this study \nis above the incidence in the literature, and according to the \nliterature, this rate is below 1% in other conducted studies.(3-5)\nIn the ovarian preservation approach, it is essential \nto determine the criteria to be used in appropriate patient \nTable 3. Receiver Operating Characteristic (ROC) curve analysis of \nNEU, NLR, and SII for predicting coexisting adnexal malignancies\nTest result \nvariable(s) Area Std. error Asymptotic \nSig.\nAsymptotic 95% \nConfidence Interval\nLower \nbound\nUpper \nbound\nNEU 0.751 0.067 0.008 0.620 0.883\nNLR 0.738 0.086 0.013 0.569 0.907\nSII 0.726 0.076 0.018 0.576 0.875\nTable 4.  Clinicopathological characteristics of patients with adnexal involvement\nPatient Age Site HS Grade FIGO \nStage\nOvarian/tubal \nmorphology LVSI\nEndocervical\nglandular \nınvolvement \nCervical \nstromal \ninvasion\nMajor intraoperative findings\nM 45 LO E 3 3 Normal - + + Cervical mass, Palpable LN\nM 33 LO S 1 3 Normal - - - Left cornual surface,5*5 cm multilobular tumural \nvegation, Palpable LN, Acid\nM 47 BO S 3 4 Normal + + + Peritoneal and omental seeding, Palpable LN\nM 48 RO E 3 4 Normal - - + Peritoneal seeding (rectosigmoid, douglas), \nPalpable LN\nM 42 RO E 3 3 Abnormal - - + RO; tumoral infiltration, Palpable LN\nM 46 BO E 3 3 Abnormal + - - LO, 7*9 cm cystic and solid; RO, 4*5 cm cystic and \nsolid, Palpable LN\nM 42 RS E 3 3 Abnormal + - - Abnormal salpinx\nM 47 LO E 2 3 Abnormal + - - LO; 3*3cm cystic and solid\nS 50 RO M 2 3 Abnormal + - - RO; 5*6cm cystic and solid\nS 43 BO S 1 1 Abnormal + - - Bilateral TOA\nM 47 RO E 1 3 Normal - - - -\nM 49 BO E 2 3 Abnormal - - + RO; 5*6 cm cystic and solid, LO; 10*15 cm cystic \nand solid\nM 48 LO U 3 3 Normal + - + Palpable LN\nS 43 BO E 1 1 Abnormal - - - RO; solid and cyst, tumoral infiltration\nM 44 BO E 1 4 Abnormal + - - Bilateral large ovary, LH, Palpable LN\nS 46 BO S 3 4 Abnomal - - - LO; 20*15 cm cystic and solid, RO; 5*6 cm cystic \nand solid, serosal tumoral infiltration (rectum)\nS 44 RO E 1 1 Abnormal - - - Large ovary, tumoral infiltration\nEn - endometrioid; S -  carcinosarcoma; U -  undifferentiated; M -  mixed; RO - right ovary; LO - left ovary; RS -  Right hydrosalpinx; TOA - Tubal ovarian abscess; LN -  lymph node; LH - Left hydrosaliınx;  LVSI -  lymphovascular space \ninvasion\n\n5\nA novel marker  in the ovarian preservation approach to endometrial cancer: systemic immune inflammatory index\nŞahin B, Gürbüz TB, Duru Çöteli SA, Begen EE, Akay A, Boran N, et al. \nRev Bras Ginecol Obstet. 2025;47:e-rbgo59.\ndisease, absence of LVSI, myometrial invasion of <50%, \nand under 45 years of age. In a most recent review in 2023, \nBizzarri et al. (20) discussed the ovarian preservation ap-\nproach in gynecological cancers. They concluded that \nthe ovarian preservation approach could be applied to pa -\ntients with FIGO stage 1A, grade 1-2, endometrioid type, and \nyounger than 40. (20) In our study, we found that advanced \nincreased grade, depth of myometrial invasion and meta -\nstatic pelvic lymph node involvement were independent \nprognostic factors. This study found that non-endome-\ntrioid histological type, increased grade, advanced stage \nof the disease, myometrial invasion depth, LVSI, cervical \nstromal invasion, lymph node metastasis, and omental in-\nvolvement were significant in predicting ovarian involve-\nment. Among these variables, it is found that the grade, \nmyometrial invasion and metastatic pelvic lymph node \ninvolvement were independent prognostic factors. When \npatients with ovarian involvement were examined, 83% of \nthe patients with micrometastatic ovarian involvement \nwere over 45 years of age. For this reason, patient selection \nfor ovarian-sparing surgery should be done carefully in the \npatient group over 45 years of age. In their meta-analysis \nevaluating the risk factors for ovarian metastasis, Liang \net al. (26) reported that data on ovarian protection in the \npostmenopausal patient group were lacking and that be-\ning over 45 remained a significant risk factor for ovarian \nrecurrence. One of the critical questions in ovarian conser -\nvation approach is survival.  The literature, reports no sta -\ntistically significant survival difference between patients \nwho have undergone salpingo-oophorectomy and those \nwho have not. (27-31) Additionally, some studies suggest that \npatients who undergo ovarian-sparing surgery have better \ndisease-free survival, but similar overall survival. (32)\nSII is a new index that reflects local immune response \nand systemic inflammation based on peripheral lympho-\ncyte, neutrophil, and platelet counts. Especially recent \nstudies show that it is effective in tumor prognosis and \nsurvival. Inflammatory changes in the tumor microenviron-\nment contribute to cancer cell proliferation, metastasis, \nangiogenesis, and immune escape. While lymphocytes are \nvaluable in generating tumor immunity, neutrophil cells \nare the effector cells of the acute inflammatory response. \nDuring a systemic infection in the body, platelet counts in-\ncrease and aggravate tumor growth. A decrease in the num-\nber of lymphocytes results in decreased tumor immunity. \nFactors that stimulate granulopoiesis and thrombopoiesis \nin tumor cells are associated with elevated SII secondary \nto systemic inflammation in EC patients. (21,22,33,34) SII plays \nan important role in survival and prognosis in gynecologic \nmalignancies.  In a recent study, high SII was presented as \nan independent risk factor for postmenopausal advanced \nEC.(23) It is known that ovarian involvement is important in \nEC prognosis. However, there is no study in the literature \nTable 5. Univariate and multivariate logistic regression analyses of \nclinicopathologic factors associated with coexisting adnexal ma -\nlignancies \nFactor\nUnivariate \nlogistic \nregression p-value*\nMultivariate \nlogistic \nregression p-value*\nOdds ratio (95% \nCI)\nOdds ratio (95% \nCI)\nStage\n   Stage 1-2 1 (reference)\n   Stage 3-4 39.2 (10.36-148.26) <0.001\nMyometrial invasion\n   No 1 (reference)\n   Yes 13.98 (4.66-41.88) <0.001 12.4 (1.49-45.92) 0.046\nLVSI\n   No 1 (reference)\n   Yes 7.06 (2.46-20.3) <0.001 - -\nCervical stromal \ninvasion\n   No 1 (reference)\n   Yes 8.77 (2.73-28.17) <0.001 - -\nMetastases to pelvic \nlymph nodes\n   No 1 (reference)\n   Yes 14.19 (4.69-42.94) <0.001 30.54 (1.96-475.72) 0.015\nMetastases to para-\naortic lymph nodes\n   No 1 (reference)\n   Yes 9.16 (2.52-33.27) 0.001 - -\nOmental involvement\n   No 1 (reference)\n   Yes 17.25 (2.65-112) 0.003 - -\nHistologic grade\n   Grade 1 1 (reference)\n   Grade 2-3 8.94 (3.05-26.19) <0.001 19.7 (1.17-350.6) 0.042\nNLR\n   < 2.63 1 (reference)\n   ≥ 2. 63 7.25 (1.47-35.7) 0.015 - -\nSII\n   < 992.58 1 (reference)\n   ≥992.58 7.4 (1.79-30.48) 0.006 1.45 (1.01-12.34) 0.034\n*SII -  Systemic immune inflammation index;  LVSI - Lymphovascular space involvement;  NLR -  Neutrophil to \nlymphocyte ratio.  Logistic regression analysis\nselection and to determine the risk factors for ovarian in-\nvolvement due to the proximity of the uterus and ovary, the \nrisk of micrometastasis to the ovary, and primary ovarian \ncancer in the following years. In a study evaluating the ad -\nvantages and disadvantages of the ovarian preservation \napproach, a two-stage evaluation was recommended in pa -\ntient selection; it was revealed that the ovarian preserva -\ntion approach could be preferred in patients with no family \nhistory of breast or ovarian cancer, no risk for Lynch syn-\ndrome, and no intraoperative findings (extrauterine metas-\ntasis, upgrade or high-grade, deep myometrial invasion, \ncervical invasion, large tumor, etc.). (3) In 2018, the National \nComprehensive Cancer Network (NCCN) (24) reported that \novarian preservation is possible in patients with no family \nhistory of ovarian or breast cancer, no Lynch syndrome, and \nmacroscopically normal ovarian appearance. Baiocchi et \nal.(25) demonstrated that the ovarian preservation approach \ncan be considered in patients with low-grade (grade 1-2) \n\n6\nA novel marker  in the ovarian preservation approach to endometrial cancer: systemic immune inflammatory index\nŞahin B, Gürbüz TB, Duru Çöteli SA, Begen EE, Akay A, Boran N, et al. \nRev Bras Ginecol Obstet. 2025;47:e-rbgo59.\nexamining the relationship between ovarian involvement \nand SII.\nThis study is the first to investigate the relationship be-\ntween ovarian involvement in preoperative SII and EC. When \nthe studies in the literature investigating the relationship \nbetween endometrial cancer and systemic immune-inflam-\nmatory index were analyzed, it was revealed that postoper -\native SII plays a role as an independent prognostic factor in \nsurvival and was also an independent risk factor in lymph \nnode metastasis. It was also identified as an essential in-\nflammatory marker in predicting myometrial invasion and \nhigh-grade cancer in the young patient population. (23,27) In \nour study, which revealed a close relationship between ovar-\nian involvement and SII in EC patients, we presented high \nSII as an independent prognostic factor for ovarian involve-\nment when patients were grouped according to a cut-off val-\nue of 992. According to the results of this study, SII should be \nconsidered an index that can be used in patient selection in \nthe ovarian preservation approach. \nThe strengths of this study include being the first to \ndiscuss the role of SII in ovarian involvement in endometrial \ncancer, including patients aged 50 and under as a sample, \nand supporting the literature in selecting patients for ovari-\nan-sparing surgery. The study’s limitations include its retro-\nspective design, few patients and not using the FIGO 2023 \nstaging system.\nConclusion\nDue to the adverse effects of early menopause on women’s \nhealth, including vasomotor symptoms, impaired bone \nhealth, dyslipidemia, and increased cardiovascular risk, \novarian preservation has gained attention in the surgical \nmanagement of endometrial cancer. Although bilateral \nsalpingo-oophorectomy (BSO) is a standard component of \ntreatment—primarily due to the risk of ovarian microme-\ntastasis, proximity of the ovaries to the uterus, and the \npersistence of endogenous hormone production—its long-\nterm consequences must be carefully weighed. According \nto our findings, ovarian-sparing surgery may be considered \na viable option in patients under 50 years of age, with ear -\nly-stage, low-grade tumors, no myometrial invasion, and no \npelvic lymph node involvement. 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Oncoimmunology. \n2019;8(12):e1662708. doi: 10.1080/2162402X.2019.1662708","source_license":"CC0","license_restricted":false}