OBJECTIVE: To evaluate patterns of recurrence and explore the prognostic differences between the 2018 FIGO staging system and the 2020 ESGO-ESTRO-ESP risk stratification system of endometrial cancer with an emphasis on early-stage disease.
BACKGROUND: The incidence of endometrial cancer has risen by around 60% since the 90\'s. It is projected that by 2035 endometrial cancer will be the sixth most common cause of cancer-related death amongst females.
METHODS: This was a retrospective cohort study which included patients treated between 2010 and 2017. Primary endpoints were overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meyer survival analysis was used to assess OS and RFS across different risk groups. Cox proportional hazards regression was used to evaluate prognostic risk factors implicated in recurrence. Different recurrence patterns across the subgroups were analysed with Pearson\'s chi-square test.
RESULTS: The study included 692 patients with a recurrence rate of 14.9%. The median time to recurrence was 17.1 months (IQR:8.8-28.4). The mean OS varied between 97.2 months in the low-risk group to 63.1 months in the high-risk group (p < 0.001). Mean RFS was 96.1 in the low-risk group and 58.9 in the high-risk group (p < 0.001). RFS was predicted by the following factors; high risk group (OR=3.87; p = 0.041), LVSI (OR=2.54, p = 0.005), carcinosarcoma (OR=2.20, p = 0.021) and serous subtype (OR=1.91, p = 0.01). Logistic regression was used to evaluate risk factors for loco-regional and distant recurrence. Patients in the low-risk group were less likely to have distant recurrence (OR=0.08, p = 0.004). Similarly, negative LVSI and Grade 1 cancers were associated with decreased risk of distant recurrence (OR=0.34, p = 0.006 and OR=0.33, p = 0.007, respectively). There were no significant risk factors for loco-regional recurrence.
CONCLUSIONS: The 2020 ESGO-ESTRO-ESP risk stratification provides accurate estimates of recurrence risk and survival. Those treated in line with current guidance have significantly better outcomes.

BACKGROUND: In 2023, the International Federation of Gynecology and Obstetrics (FIGO) updated the endometrial cancer staging system (FIGO2023). Our study aimed to validate the prognostic value of FIGO2023 in patients with early-stage EC (Stage I and Stage II).
METHODS: After screening eligible EC patients from the Surveillance, Epidemiology and End Results (SEER) database, Kaplan-Meier cancer-specific survival (CSS) curves were used to evaluate the prognosis of patients with different stages. In addition, AUC, C-index, Akaike Information Criterion (AIC), Bayesian Information Criterion (BIC), and Decision curve analysis (DCA) were used to comprehensively compare the efficacy of the new and the old staging system in predicting prognosis.
RESULTS: A total of 33,156 patients were enrolled. The introduction of FIGO2023 significantly increased the proportion of stage II patients from 5.53 % to 24.76 %. The FIGO2023 defines different substages for patients, which show significant differences in CSS. Compared with FIGO2009, FIGO2023 performed better in discrimination, goodness of fit and clinical decision making.
CONCLUSIONS: Compared with FIGO2009, FIGO2023 had a higher accuracy in predicting CSS in patients with early-stage EC in the SEER database.

OBJECTIVE: This study aimed to systematically examine the relationship between polycystic ovary syndrome and ovarian, endometrial, and cervical cancers using the National Inpatient Sample (NIS) database.
METHODS: We utilized the International Classification of Diseases (ICD-10) system to identify relevant codes from the NIS database (2016-2019). Univariate and multivariable regression analyses (adjusted age, race, hospital region, hospital teaching status, income Zip score, smoking, alcohol use, and hormonal replacement therapy) were conducted to evaluate association between PCOS and gynecologic cancers. Results were summarized as odds ratio (OR) with 95% confidence intervals (CI).
RESULTS: Overall, 15,024,965 patients were analyzed, of whom 56,183 and 14,968,782 patients were diagnosed with and without PCOS, respectively. Among the patients diagnosed with gynecologic cancers (n = 91,599), there were 286 with PCOS and 91,313 without PCOS. Univariate analysis revealed that PCOS was significantly associated with higher risk of endometrial cancer (OR = 1.39, 95 % CI [1.18-1.63], p < 0.0001), but lower risk of ovarian cancer (OR = 0.55, 95 % CI [0.45-0.67], p < 0.0001) and cervical cancer (OR = 0.68, 95 % CI [0.51-0.91], p = 0.009). In contrast, after Bonferroni correction, multivariable analysis depicted that PCOS remained significantly associated with higher risk of endometrial cancer (OR = 3.90, 95 % CI [4.32-4.59], p < 0.0001). There was no significant correlation between PCOS and risk of ovarian cancer (OR = 1.09, 95 % CI [0.89-1.34], p = 0.409) and cervical cancer (OR = 0.83, 95 % CI [0.62-1.11], p = 0.218).
CONCLUSIONS: This first-ever NIS analysis showed that patients with PCOS exhibited unique gynecologic cancer risk profiles, with higher risk for endometrial cancer, and no significant risk for ovarian or cervical cancers.

OBJECTIVE: Demographic change and increasing complexity of therapy decisions lead to a growing burden on the healthcare system, necessitating efforts to simplify and enhance the efficiency of patient care. The present study evaluates ChatGPT\'s ability to provide therapy recommendations for gynecological malignancies that are both in line with the local guidelines and individually tailored to the patient.
METHODS: Sixteen patients with endometrial, cervical, and ovarian cancer who were treated in the gynecological clinic of the University Hospital Erlangen from January 2022 to August 2023 were included in the analysis. Data collected within clinical routine care were communicated to the chat-based AI model ChatGPT (version 3.5). ChatGPT\'s performance generating treatment plans were evaluated using an answer scoring system and descriptive analysis.
RESULTS: According to the answer scoring system [range: -1 point (minimum) to 2 points (maximum)], ChatGPT demonstrated a good potential in generating therapy recommendations with an average score of 0.75 points for patients with ovarian cancer, 0.7 points for cervical and 1.5 points for endometrial cancer patients. The most common deductions in points were about incomplete therapy recommendations, whereas contraindicated treatment modalities were rarely suggested. Individual patient characteristics were regularly considered by ChatGPT. ChatGPT reliably indicated aftercare and provided detailed information on preventive measures as well as supportive treatment.
CONCLUSIONS: ChatGPT is a promising tool for the generation of therapy suggestions for gynecological carcinomas with high flexibility in response to individual patient differences. At the current state, however, ChatGPT is not suitable for replacing expert panels.

CD8+ T cells are the primary mediators of anticancer immunity, and modulation of the CD8+ T cell response has been a central focus of immunotherapy to treat cancer. When CD8+ T cells specifically recognize antigenic peptides presented by the MHC-I on tumor cells, they become activated and kill the tumor cells. However, one pivotal mechanism through which tumor cells evade immune surveillance is to reduce their antigen presentation. To identify novel immunotherapeutic targets, we specifically focused on the role of MAL2 in immune evasion in endometrial cancer (EC) and the underlying mechanism. MAL2 was overexpressed in EC tissues and cells and its transcription was enhanced by RAD21. Knockdown of MAL2 or RAD21 inhibited malignant behavior and immune evasion of EC cells by repressing MHC-I expression and the cytotoxic effects of CD8+ cells. Conversely, MAL2 promoted immune evasion of EC cells and tumor growth in mice in the presence of RAD21 knockdown. These results indicate that RAD21 activation of MAL2 inhibits antigen processing and presentation of MHC-I, thereby inducing immune evasion of EC cells. We further suggest that RAD21 and MAL2 may serve as novel targets for EC immunotherapy.

UNASSIGNED: The aim of our study was to assess overall survival and cancer-specific survival in endometrial cancer patients with type 2 diabetes mellitus (T2DM) using metformin.
UNASSIGNED: Patients with endometrial cancer and T2DM during 2000-2012 period were identified from the Lithuanian Cancer Registry and the National Health Insurance Fund database. Cancer-specific and overall survival were primary outcomes.
UNASSIGNED: In our study we included 6287 women with endometrial cancer out of whom 664 were diagnosed with T2DM (598 metformin users and 66 never users). During follow-up (mean follow-up time was 8.97 years), no differences in risk of endometrial cancer specific mortality was observed in diabetic patients treated with metformin (Hazard Ratio (HR) 0.87, 95% Confidence Interval (CI) 0.70-1.07). Overall mortality in the diabetic metformin ever users\' group was significantly higher compared with the non-diabetic endometrial cancer women (HR 1.17, 95% CI 1.03-1.32) and in the group of metformin never users with T2DM (HR 1.42, 95% CI 1.07-1.87).
UNASSIGNED: Our study results suggest no beneficial impact on overall and cancer-specific survival in endometrial cancer patients who were treated with metformin as part of their diabetes treatment.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s40200-023-01358-3.

BACKGROUND: The endometrium remains a difficult tissue for the analysis of microbiota, mainly due to the low bacterial presence and the sampling procedures. Among its pathologies, endometrial cancer has not yet been completely investigated for its relationship with microbiota composition. In this work, we report on possible correlations between endometrial microbiota dysbiosis and endometrial cancer.
METHODS: Women with endometrial cancer at various stages of tumor progression were enrolled together with women with a benign polymyomatous uterus as the control. Analyses were performed using biopsies collected at two specific endometrial sites during the surgery. This study adopted two approaches: the absolute quantification of the bacterial load, using droplet digital PCR (ddPCR), and the analysis of the bacterial composition, using a deep metabarcoding NGS procedure.
RESULTS: ddPCR provided the first-ever assessment of the absolute quantification of bacterial DNA in the endometrium, confirming a generally low microbial abundance. Metabarcoding analysis revealed a different microbiota distribution in the two endometrial sites, regardless of pathology, accompanied by an overall higher prevalence of pathogenic bacterial genera in cancerous tissues.
CONCLUSIONS: These results pave the way for future studies aimed at identifying potential biomarkers and gaining a deeper understanding of the role of bacteria associated with tumors.

The purpose of this study was to establish the noninferiority of robotic single-site (RSS) surgery compared with multiport laparoscopic (MPL) surgery in surgical outcomes and overall survival for early endometrial cancer. This study was conducted retrospectively in a single center and included 421 patients who underwent either RSS (n = 146) or MPL (n = 275) surgery between 2014 and 2022. In terms of perioperative outcomes, the RSS group had a longer operating time than the MPL surgery group (mean (standard deviation [SD]) RSS 97.55 [29.79] vs. MPL 85.56 [26.13], p < 0.001). However, no significant differences in estimated blood loss or perioperative complications were found between the groups (p = 0.196 and p = 0.080, respectively). The patients in the RSS group were discharged earlier than those in the MPL group (mean [SD]): 4.06 [3.24] vs. 9.39 [4.76], p < 0.001). Regarding oncologic outcomes, no significant differences in the type of therapy, disease stage, tumor grade, histopathological type, or lymphovascular invasion were found between the groups. No statistically significant differences were found in the disease-free (p = 0.27) and overall survival rates (p = 0.5) either. In conclusion, this study suggests that RSS and MPL surgery are both safe and effective options for staging operations in patients with early-stage endometrial cancer.

Endometrial cancer (EC) is one of the most common malignant tumors among women in the 21st century, whose mortality rate is increasing every year. Currently, the diagnosis of EC is possible only after a biopsy. However, it is necessary to find a new biomarker that will help in both the diagnosis and treatment of EC in a non-invasive way. Circular RNAs (circRNAs) are small, covalently closed spherical and stable long non-coding RNAs (lncRNAs) molecules, which are abundant in both body fluids and human tissues and are expressed in various ways. Considering the new molecular classification of EC, many studies have appeared, describing new insights into the functions and mechanisms of circRNAs in EC. In this review article, we focused on the problem of EC and the molecular aspects of its division, as well as the biogenesis, functions, and diagnostic and clinical significance of circRNAs in EC.

Endometrial cancer (EC) includes various histologic types, with estrogen-dependent endometrioid carcinoma being the most common. Obesity significantly increases the risk of developing this type, especially in postmenopausal women, due to elevated estrogen production by adipocytes. This review examines the impact of weight loss from different interventions on reducing obesity-related risk factors for endometrioid EC. A systematic review and meta-analysis were conducted on three weight loss interventions: bariatric surgery, pharmacotherapy, and lifestyle changes. The effects of these interventions on inflammatory biomarkers (CRP, TNF-α, IL-6) and hormones (leptin, estrogen) were analyzed. Data from controlled studies were pooled to assess the significance of weight loss in reducing these biomarkers. Despite heterogeneity, bariatric surgery resulted in an overall 25.8% weight reduction, outperforming lifestyle and pharmacotherapy interventions. Weight loss reduced CRP levels by 33.5% and IL-6 levels by 41.9%. TNF-α levels decreased by 13% with percent weight loss over 7%. Leptin levels also decreased significantly, although the exact weight loss percentage was not statistically significant. Weight loss effectively reduces proinflammatory markers and hormones associated with increased risk of endometrioid EC. The strengths of this review include a comprehensive examination of different weight-loss interventions and a large pool of participants. However, limitations include high heterogeneity among studies and only 43% of the participants being postmenopausal. Limited data on sex hormones and racial disparities underscore the need for further research.