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Simple Summary: The optimal selection of patients with advanced high-grade serous ovarian cancer (HGSOC) who are likely to benefit from upfront cytoreductive surgery remains challenging. With the results of the TRUST trial, the fifth randomized phase III trial comparing oncologic outcomes of primary versus interval cytoreductive surgery, expected to be presented soon, there is a high unmet clinical need to define novel biomarkers to optimize pretherapeutic patient assessment and allow for more personalized clinical decision making. Building on the growing evidence of the predictive and prognostic value of fibrinogen in various solid cancers, this study is the first to observe an independent association between the "Fibrinogen–Albumin-Ratio Index" (FARI) and surgical outcomes in patients with advanced HGSOC undergoing primary cytoreductive surgery. Given that the FARI seems to act as a surrogate for intra-abdominal tumor load, the further clinical validation of this cost-effective and readily available biomarker appears promising. Background/Objectives: The present study evaluates predictive implications of the pretherapeutic Fibrinogen–Albumin-Ratio Index (FARI) in high-grade serous ovarian cancer (HGSOC) patients undergoing primary cytoreductive surgery. Methods: This retrospective study included 161 patients with HGSOC International Federation of Gynecology and Obstetrics (FIGO) stage ≥ IIb, who underwent primary cytoreductive surgery followed by platinum-based chemotherapy. Associations between the FARI and complete tumor resection status were described by receiver operating characteristics, and binary logistic regression models were fitted. Results: Higher preoperative FARI values correlated with higher ascites volumes (r = 0.371, p < 0.001), and higher CA125 levels (r = 0.271, p = 0.001). A high FARI cut at its median (≥11.06) was associated with lower rates of complete tumor resection (OR 3.13, 95% CI [1.63–6.05], p = 0.001), and retrained its predictive value in a multivariable model independent of ascites volumes, CA125 levels, FIGO stage, and Charlson Comorbidity Index (CCI). Conclusions: The FARI appears to act as a surrogate for higher intra-abdominal tumor load. After clinical validation, FARI could serve as a readily available serologic biomarker to complement preoperative patient assessment, helping to identify patients who are likely to achieve complete tumor resection during primary cytoreductive surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: Low-grade serous ovarian cancer is a rare and complex subtype that usually develops slowly and predominantly affects younger women. Conventional treatment, which generally involves a combination of primary surgery and chemotherapy, often fails, leading to frequent recurrences. Due to the rarity of this cancer subtype, there are limited clinical data available to guide optimal treatment decisions. However, recent research is focusing on new, promising therapies, including targeted treatments that address specific molecular pathways and hormonal therapies. These emerging options offer hope for improved outcomes by enabling more personalized and effective management. This review aims to address the current treatment challenges and summarize the innovative therapies and their potential to enhance treatment strategies, aiming to provide better management for patients with this uncommon ovarian cancer subtype. Low-grade serous ovarian carcinoma (LGSOC) is a rare subtype of epithelial ovarian cancer, characterized by a unique molecular background and specific clinical behavior. A growing body of molecular data underscores LGSOC as a distinct disease entity; however, clinical evidence on the optimal treatment regimens for LGSOC remains limited due to the low incidence of the disease. Consequently, treatment recommendations for LGSOC are still often derived from findings on the more common high-grade serous ovarian carcinoma (HGSOC) and typically focus on radical cytoreductive surgery and platinum-based chemotherapy. Since LGSOCs typically exhibit only limited responsiveness to platinum-based chemotherapy, the clinical management of advanced and recurrent LGSOCs remains a significant therapeutic challenge and often results in limited treatment options and suboptimal outcomes. Recent advances in molecular profiling and the identification of new, promising targets, such as the mitogen-activated protein kinase (MAPK) pathway, offer hope for improving both the prognosis and health-related quality of life in affected patients. Given the high unmet clinical need to establish new therapeutic standards beyond cytotoxic chemotherapy, this review aims to summarize the most promising molecular targets and emerging targeted agents. [ABSTRACT FROM AUTHOR]

Simple Summary: The availability of multiple gene panel testing allows us to identify germline pathogenic variants of validated cancer genes. We evaluated the prevalence and clinical/prognostic impact of deleterious germline mutations in OC patients. Germline panel testing should be performed for all patients with ovarian cancer. Better prognosis was found for germline mutated ovarian cancer patients. Endometrioid and clear cell histology subtypes show more deleterious mutations in other genes. Data on deleterious variants in genes other than BRCA1/2 remain limited. A retrospective cohort study was performed, including primary OC cases with TruRisk® germline gene panel testing between 2011 and 2020. Patients with testing after relapse were excluded. The cohort was divided into three groups: (A) no mutations, (B) deleterious BRCA1/2 mutations, and (C) deleterious mutations in other genes. A total of 702 patients met the inclusion criteria. Of these 17.4% (n = 122) showed BRCA1/2 mutations and a further 6.0% (n = 42) in other genes. Three-year overall survival (OS) of the entire cohort was significantly longer in patients with germline mutations (85%/82.8% for cohort B/C vs. 70.2% for cohort A, p < 0.001) and 3-year progression-free survival (PFS) only for cohort B (58.1% vs. 36.9%/41.6% in cohort A/C, p = 0.002). In multivariate analysis for the subgroup of advanced-stages of high-grade serous OC, both cohorts B/C were found to be independent factors for significantly better outcome, cohort C for OS (HR 0.46; 95% CI 0.25–0.84), and cohort B for both OS and PFS (HR 0.40; 95% CI 0.27–0.61 and HR 0.49; 95% CI 0.37–0.66, respectively). Germline mutations were detected in a quarter of OC patients, and a quarter of those in genes other than BRCA1/2. Germline mutations demonstrate in our cohort a prognostic factor and predict better prognosis for OC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Testing for a homologous recombination deficiency (HRD) in primary high-grade ovarian cancer is crucial for recommending the appropriate therapy. Patients with a BRCA germline mutation are defined as harboring an HRD deficiency. However, there is a group of approximately 20% of patients without a BRCA mutation which harbor an HRD deficiency based on tumor genomic analyses. In the current research, we wanted to share the experience of a high-volume tertiary cancer center with implementing central HRD testing—in another institution—to reduce doubts about logistic issues and to the highlight critical aspects that hinder HRD testing. We showed that the results of HRD testing became available in a timely manner for the therapy decision. However, it was important to obtain as much tumor tissue as possible during the first diagnosis—before any other intervention—as the tumor quantity and quality were critical for HRD testing. Additional BRCA germline testing further reduced the failures of HRD testing and should additionally be routinely conducted. The chemotherapy backbone for patients with high-grade advanced epithelial ovarian cancer (HG-AOC) is carboplatin and paclitaxel followed by a maintenance therapy either with bevacizumab, with a PARP inhibitor, or with a combination of both, which is defined by the presence of a homologous recombination deficiency (HRD) and by the BRCA1/2 status. This study included patients with a primary diagnosis of HG-AOC treated between December 2019 and December 2021. The HRD status was measured using the Myriad myChoice® test on all the patients with an indication for tumor HRD testing. Germline testing was conducted on all the patients using the TruRisk® panel as recommended by the national guidelines. HRD testing was requested for 190 patients, and, for 163 patients (85.8%), an HRD test result was available. An HRD test result could not be reported in 27 patients due to an insufficient tumor yield. The median time that it took to receive the HRD test results was 37 days (range of 8–97). In total, an HRD was present in 44.7% (73/163) of the patients based on a GIS ≥ 42 in 42.9% of the patients and based on a tumor BRCA1/2 mutation in 3 cases (all with a GIS < 42). The germline testing results were available for 148 patients, and, in 18 patients (12.2%), a deleterious germline mutation was detected. Of the 27 patients without sufficient HRD testing, BRCA1/2 germline testing results were available for 19 patients (70.4%), and a deleterious germline mutation was detected in 2 patients (7.4%). The implementation of HRD testing is feasible, and the results become available for treatment decisions in a timely manner for most patients. The prerequisite for HRD testing with the Myriad myChoice® test is a sufficient amount of tumor tissue. The cotesting of HRD and BRCA1/2 germline testing should be aimed for in order to enable optimal and timely treatment decisions on maintenance therapy as well as to test patients on whom the HRD test will not be evaluable. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian cancer (OC) is the deadliest genital tumor in women. In this multicenter study, we developed three new diagnostic models based on serum proteins and patient age. All models were then validated using data from centers other than those used for the model development. We also compared the performance of these models with common singular markers (CA125, HE4) and algorithms (ROMA-50 and the Copenhagen Index). We used modern technology (Luminex®, Austin, TX, USA) that enables the simultaneous determination of several biomarkers in a small amount of blood. A combination of patient age with four to six markers performed best: CA125, osteopontin, prolactin, macrophage migration inhibitory factor, and, eventually, HE4 and leptin. Our models were better than the ROMA-50 index but did not outperform the Copenhagen Index. In postmenopausal patients, all the newly developed models performed excellently. Unfortunately, none of the models tested improved the diagnosis in premenopausal patients and those missed due to normal CA125 levels. Ovarian cancer (OC) is the most lethal genital malignancy in women. We aimed to develop and validate new proteomic-based models for non-invasive diagnosis of OC. We also compared them to the modified Risk of Ovarian Malignancy Algorithm (ROMA-50), the Copenhagen Index (CPH-I) and our earlier Proteomic Model 2017. Biomarkers were assessed using bead-based multiplex technology (Luminex®) in 356 women (250 with malignant and 106 with benign ovarian tumors) from five European centers. The training cohort included 279 women from three centers, and the validation cohort 77 women from two other centers. Of six previously studied serum proteins (CA125, HE4, osteopontin [OPN], prolactin, leptin, and macrophage migration inhibitory factor [MIF]), four contributed significantly to the Proteomic Model 2021 (CA125, OPN, prolactin, MIF), while leptin and HE4 were omitted by the algorithm. The Proteomic Model 2021 revealed a c-index of 0.98 (95% CI 0.96, 0.99) in the training cohort; however, in the validation cohort it only achieved a c-index of 0.82 (95% CI 0.72, 0.91). Adding patient age to the Proteomic Model 2021 constituted the Combined Model 2021, with a c-index of 0.99 (95% CI 0.97, 1) in the training cohort and a c-index of 0.86 (95% CI 0.78, 0.95) in the validation cohort. The Full Combined Model 2021 (all six proteins with age) yielded a c-index of 0.98 (95% CI 0.97, 0.99) in the training cohort and a c-index of 0.89 (95% CI 0.81, 0.97) in the validation cohort. The validation of our previous Proteomic Model 2017, as well as the ROMA-50 and CPH-I revealed a c-index of 0.9 (95% CI 0.82, 0.97), 0.54 (95% CI 0.38, 0.69) and 0.92 (95% CI 0.85, 0.98), respectively. In postmenopausal women, the three newly developed models all achieved a specificity of 1.00, a positive predictive value (PPV) of 1.00, and a sensitivity of >0.9. Performance in women under 50 years of age (c-index below 0.6) or with normal CA125 (c-index close to 0.5) was poor. CA125 and OPN had the best discriminating power as single markers. In summary, the CPH-I, the two combined 2021 Models, and the Proteomic Model 2017 showed satisfactory diagnostic accuracies, with no clear superiority of either model. Notably, although combining values of only four proteins with age, the Combined Model 2021 performed comparably to the Full Combined Model 2021. The models confirmed their exceptional diagnostic performance in women aged ≥50. All models outperformed the ROMA-50. [ABSTRACT FROM AUTHOR]

The European Society of Gynaecological Oncology (ESGO), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis (IOTA) group, and the European Society for Gynaecological Endoscopy (ESGE) jointly developed clinically relevant and evidence-based statements on the pre-operative diagnosis of ovarian tumors, including imaging techniques, biomarkers, and prediction models. ESGO/ISUOG/IOTA/ESGE nominated a multidisciplinary international group, including expert practising clinicians and researchers who have demonstrated leadership and expertise in the pre-operative diagnosis of ovarian tumors and management of patients with ovarian cancer (19 experts across Europe). A patient representative was also included in the group. To ensure that the statements were evidence-based, the current literature was reviewed and critically appraised. Preliminary statements were drafted based on the review of the relevant literature. During a conference call, the whole group discussed each preliminary statement and a first round of voting was carried out. Statements were removed when a consensus among group members was not obtained. The voters had the opportunity to provide comments/suggestions with their votes. The statements were then revised accordingly. Another round of voting was carried out according to the same rules to allow the whole group to evaluate the revised version of the statements. The group achieved consensus on 18 statements. This Consensus Statement presents these ESGO/ISUOG/IOTA/ESGE statements on the pre-operative diagnosis of ovarian tumors and the assessment of carcinomatosis, together with a summary of the evidence supporting each statement. [ABSTRACT FROM AUTHOR]

Background: An increasing body of evidence shows that miR-34 family has tumor suppressive properties mediating apoptosis, cell cycle arrest and senescence. In ovarian cancer, miR34 family members were found to be under expressed. Particularly miR-34a has been revealed to be a direct transcriptional target of p53 which is frequently mutated in epithelial ovarian carcinomas especially in high grade serous cancer. Moreover, methylation of miR-34a CpG Islands was found to down-regulate miR-34a expression. The aim of this study was to investigate the clinical relevance of mir34a as well as its promoter methylation in a subset of 133 ovarian cancers with a special focus on the p53 mutation status, the dualistic type I and type II ovarian cancer model and the different histotypes.Methods: One hundred thirty-three epithelial ovarian cancers and 8 samples of healthy ovarian surface epithelium were retrospectively analysed for miR-34a expression with quantitative real-time reverse transcription PCR (qRT-PCR). Gene-specific DNA methylation was evaluated with MethyLight technique.Results: Significantly lower miR-34a expression was found in ovarian cancers than in healthy ovarian epithelium (p = 0.002). The expression of miR-34a was found lower in type II than in type I cancers (p = 0.037), in p53 mutated as compared to p53 wild type cancers (p = 0.003) and in high grade compared to in low grade cancers (p = 0.028). In multivariate COX regression model low expressing miR-34a cancers exhibited a reduced PFS (p = 0.039) and OS (p = 0.018). In serous cancers low miR-34a levels showed a worse OS confirmed also in multivariate analysis (p = 0.022). miR-34a promoter methylation was found higher in type II cancers than in type I (p = 0.006). mir34a expression and promoter methylation showed an inverse correlation in cancer samples (p = 0.05).Conclusion: We demonstrated a clinical independent role of miR-34a in epithelial ovarian cancers. Moreover, we corroborated the correlation between miR-34a expression and its promoter methylation in a large set of ovarian cancers. The inverse association between miR-34a expression and grading, p53 mutation status and dualistic tumor type classification, together with its prognostic relevance may underline the tumor-suppressive character of miR-34a in ovarian cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Advances in circulating tumor cells (CTCs) research could improve the way we diagnose, treat and monitor epithelial ovarian cancer (EOC) patients. In this study, we investigated the interplay between inflammation-induced systemic catabolic markers and the presence of CTCs and patient outcome, and showed that the presence of CTCs goes hand-in-hand with an increased protein turnover and immune activation. We integrated the information provided by measuring the plasma levels of albumin, tryptophan and its metabolite kynurenine in a combined score for cancer exhaustion (CCES). Our study indicates that not only could the CCES be a useful prognostic biomarker in women with EOC, but also that the interaction between the systemic microenvironment and CTCs is worth investigating in further studies. We investigated the prognostic role of systemic characteristics for cancer exhaustion and the presence of circulating tumor cells (CTCs) in primary epithelial ovarian cancer (EOC) patients. We included 185 patients in this multicenter study with a median follow-up time of 10.25 years. Albumin, c-reactive protein (CRP) and the kynurenine to tryptophan ratio (Kyn/Trp) as well as the CTC-related marker cyclophilin C (PPIC) were obtained before primary therapy and were correlated to the respective clinical and outcome data. The information provided by albumin and Kyn/Trp was integrated in a combined score for cancer exhaustion (CCES). A high CCES characterized by hypoalbuminemia and a high Kyn/Trp was associated with both decreased overall and progression-free survival, independent from other known prognostic factors in a multivariable analysis. The presence of PPIC-positive CTCs was significantly associated with a high CCES, highlighting that the interplay between the systemic microenvironment and CTCs should be considered in "liquid biopsy" biomarker assessment. [ABSTRACT FROM AUTHOR]

: ObjectiveA relatively high incidence of pelvic and paraaortic lymph node metastases is found in patients with pT1 and pT2 ovarian cancer. This paper investigates the clinicomorphological parameters and the expression of various biological markers in these tumors in order to define possible risk factors for lymphatic dissemination.: MethodsIn a retrospective study we identified 51 patients with pT1 and pT2 ovarian cancer. All patients underwent total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and systemic pelvic ± paraaortal lymphadenectomy. The incidence of lymph node metastases in these patients and the clinicomorphological parameters of their tumors were examined. Immunohistochemistry was used to determine the expression levels of the cell proliferation marker Ki-67, the cell adhesion molecules CD44s and CD44v6, and the oncoprotein HER2/neu of the tumors and their respective lymph node metastases.: ResultsLymph node involvement was found in 5 of 26 patients with pT1 ovarian cancer and in 6 of 25 patients with pT2 ovarian cancer. Serous adenocarcinoma was associated with a significantly higher incidence of lymph node metastases than other histological types (χ2 = 4.7, P = 0.03). No correlation was found between tumor grade and the lymph node status. High Ki-67 expression was significantly correlated with spread to the lymph nodes (χ2 = 4.2, P = 0.04), whereas expression of CD44s, CD44v6, and HER2/neu was not related to the lymph node status. Survival analyses showed no difference in disease-free and overall survival in patients with lymph node metastases compared to those without lymph node metastases. No association was seen among histological type, tumor grade, and immunohistochemically detected Ki-67, CD44s, CD44v6, and HER2/neu expression on the one hand and disease-free and overall survival on the other hand.: ConclusionsOur data suggest that in early stage ovarian cancer the serous histological type and tumors showing a high Ki-67 expression carry a high risk of lymph node metastases. With respect to prognosis our data showed a minor role for Ki-67, CD44s, CD44v6, and HER2/neu expression and the occurrence of lymph node metastases in pT1 and pT2 ovarian cancer. [Copyright &y& Elsevier]

Simple Summary: In ovarian cancer, often diagnosed at an advanced stage and associated with poor overall survival, with just a third of women surviving five years, the controversial prognostic value of circulating tumor cells (CTCs) is still discussed. Currently CTC diagnostics use either molecular approaches or immunofluorescent staining. Our study shows that, given the heterogeneity and extreme scarcity of CTCs, a multifactorial analysis of CTCs is key. Combining both approaches, qPCR and IF, increased sensitivity and may better capture a treatment-related shift in the molecular phenotypes of CTCs. In addition to a long progression-free interval, the absence of CTCs after treatment was an independent predictor of an excellent outcome in patients who had already survived for five years. Thus, a multifactorial CTC approach can identify patients who have elevated risk of recurrence and death and who may require risk-adapted treatment strategies. Introduction: We previously reported the prognostic impact of circulating tumor cells (CTCs) in a multicenter study on minimal residual disease in primary ovarian cancer. With additional follow-up data, we evaluated the combined CTC approach (CTCscombo), in particular for the patients who had survived more than five years. Material and Methods: Blood samples taken at baseline and six months after adjuvant treatment (follow-up) were assessed by quantitative PCR (qPCR) measuring PPIC transcripts and immunofluorescent staining (IF). A positive result with either IF or qPCR was classified as CTCcombo-positive. Further, PPIC was assessed in the primary tumor tissue. Results: The concordance of IF and qPCR was 65% at baseline and 83% after treatment. Results showed that 50.5% of the baseline and 29.5% of the follow-up samples were CTCcombo-positive. CTCscombo after treatment were associated with increased mortality after adjusting for FIGO stage (HR 2.574, 95% CI: 1.227–5.398, p = 0.012), a higher risk of recurrence after adjusting for peritoneal carcinosis (HR 4.068, 95% CI: 1.948–8.498, p < 0.001), and increased mortality after five survived years. Discussion: The two-sided analytical approach revealed CTC subpopulations associated with ovarian cancer progression and may illuminate a potential treatment-related shift in molecular phenotypes. That approach can identify patients who have elevated risk of recurrence and death due to ovarian cancer and who may require risk-adapted treatment strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: The heterogeneity of epithelial ovarian cancer and its associated molecular biological characteristics are continuously integrated in the development of therapy guidelines. In a next step, future therapy recommendations might also be able to focus on the patient's systemic status, not only the tumor's molecular pattern. Therefore, new methods to identify and validate host-related biomarkers need to be established. Using mass spectrometry, we developed and independently validated a blood-based proteomic classifier, stratifying epithelial ovarian cancer patients into good and poor survival groups. We also determined an age dependence of the prognostic performance of this classifier and its association with important biological processes. This work highlights that, just like molecular markers of the tumor itself, the systemic condition of a patient (partly reflected in proteomic patterns) also influences survival and therapy response and could therefore be integrated into future processes of therapy planning. Mass-spectrometry-based analyses have identified a variety of candidate protein biomarkers that might be crucial for epithelial ovarian cancer (EOC) development and therapy response. Comprehensive validation studies of the biological and clinical implications of proteomics are needed to advance them toward clinical use. Using the Deep MALDI method of mass spectrometry, we developed and independently validated (development cohort: n = 199, validation cohort: n = 135) a blood-based proteomic classifier, stratifying EOC patients into good and poor survival groups. We also determined an age dependency of the prognostic performance of this classifier, and our protein set enrichment analysis showed that the good and poor proteomic phenotypes were associated with, respectively, lower and higher levels of complement activation, inflammatory response, and acute phase reactants. This work highlights that, just like molecular markers of the tumor itself, the systemic condition of a patient (partly reflected in proteomic patterns) also influences survival and therapy response in a subset of ovarian cancer patients and could therefore be integrated into future processes of therapy planning. [ABSTRACT FROM AUTHOR]

The European Society of Gynaecological Oncology and the European Society for Paediatric Oncology jointly developed clinically relevant and evidence-based guidelines for the management of adolescents and young adults aged 15 to 25 years with non-epithelial ovarian cancers, including malignant ovarian germ cell tumours, sex cord-stromal tumours, and small cell carcinoma of the ovary of hypercalcaemic type. The developmental process of these guidelines is based on a systematic literature review and critical appraisal process involving an international multidisciplinary developmental group consisting of experts from relevant disciplines (paediatric oncology, paediatric surgery, medical oncology, pathology, psycho-oncology, gynaecological oncology, and reproductive endocrinology). Given the specific and often complex issues involved in treating this group of patients, fertility sparing surgery and decrease of acute and long-term toxicities from treatment were important criteria for guidelines definition. Prior to publication, the guidelines were reviewed by 54 independent international practitioners in cancer care delivery. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the disease-free survival (DFS) and overall survival (OS) of patients with grade 1–2 endometrioid ovarian carcinoma apparently confined to the ovary, according to surgical staging. Multicenter, retrospective, observational cohort study. Patients with endometrioid ovarian carcinoma, surgical procedure performed between May 1985 and December 2019, stage pT1 N0/N1/Nx, grade 1–2 were included. Patients were stratified according to lymphadenectomy (defined as removal of any lymph node versus no lymph node assessment), and subgroup analyses according to tumor grade were performed. Kaplan-Meier curves and cox regression analyses were used to perform survival analyses. 298 patients were included. 199 (66.8 %) patients underwent lymph node assessment. Of these, 166 (83.4 %) had unilateral/bilateral pelvic and para-aortic/caval lymphadenectomy. Eleven (5.5 %) patients of those who underwent lymph node assessment showed pathologic metastatic lymph nodes (FIGO stage IIIA1). Twenty-seven patients (9.1 %) had synchronous endometrioid endometrial cancer. After a median follow up of 45 months (95 %CI:37.5–52.5), 5-year DFS and OS of the entire cohort were 89.8 % and 96.2 %, respectively. Age ≤ 51 years (HR=0.24, 95 %CI:0.06–0.91; p = 0.036) and performance of lymphadenectomy (HR=0.25, 95 %CI: 0.07–0.82; p = 0.022) represented independent protective factors toward risk of death. Patients undergoing lymphadenectomy had better 5-year DFS and OS compared to those not receiving lymphadenectomy, 92.0 % versus 85.6 % (p = 0.016) and 97.7 % versus 92.8 % (p = 0.013), respectively. This result was confirmed after exclusion of node-positive patients. When stratifying according to tumor grade (node-positive excluded), patients with grade 2 who underwent lymphadenectomy had better 5-year DFS and OS than those without lymphadenectomy (93.0 % versus 83.1 %, p = 0.040 % and 96.5 % versus 90.6 %, p = 0.037, respectively). Staging lymphadenectomy in grade 2 endometrioid ovarian carcinoma patients was associated with improved DFS and OS. Grade 1 and grade 2 might be considered as two different entities, which could benefit from different approach in terms of surgical staging. Prospective studies, including molecular profiles are needed to confirm the survival drivers in this rare setting. • Prognostic role of lymphadenectomy in G1-2 endometrioid ovarian cancer is unclear. • 5.5 % patients showed pathologic metastatic lymph nodes. • 81.8 % of node-positive patients were diagnosed with grade 2 disease. • Synchronous endometrial and ovarian cancer did not affect survival. • Staging lymphadenectomy in G2 patients was associated with improved survival. [ABSTRACT FROM AUTHOR]