Non-endometrioid Endometrial Cancer Research Articles

Performance of transvaginal ultrasound in evaluation of endometrioid versus non-endometrioid cancers.

401 Background: Measurement of endometrial thickness by transvaginal ultrasound (TVUS) is the standard of care for evaluation of patients with postmenopausal bleeding, the most common presenting symptom of endometrial cancer. However, the sensitivity of TVUS has not been clearly established in the setting of non-endometrioid histology, which is more aggressive and does not arise from endometrial hyperplasia. This study aims to evaluate the endometrial stripe (EMS) detection rate and sensitivity of TVUS in non-endometrioid compared to endometrioid endometrial cancers. Methods: In this retrospective cohort study, we included endometrial cancer cases diagnosed at a single institution from 01/01/2019 to 04/01/2024 who were enrolled in the Discovery and Evaluation of Testing for Endometrial Cancer in Tampons (DETECT) study who had TVUS during their initial clinical evaluation. Demographic characteristics and results from TVUS reports were obtained from the electronic medical record. Endometrial stripe thickness of less than 5mm is considered a negative result, whereas endometrial thickness of 5mm or greater (5mm+) is considered positive. The primary outcomes were the ability to measure EMS and the sensitivity of TVUS at a cutoff of 5mm+ for endometrial cancer detection, overall and by race and histology. We assessed differences using chi-squared tests. Results: Of the 349 patients included in our analysis, 247 (71%) had endometrioid histology, and 102 (21%) had non-endometrioid histology. There were 98 (28%) Black patients (49% non-endometrioid) and 242 (69%) White patients (22% non-endometrioid). The EMS was adequately measured in 98% of patients with endometrioid histology compared to 91% of patients with non-endometrioid histology (p=0.001). When stratified by race, EMS was visualized in 100% of Black patients with endometrioid histology but 89% of Black patients with non-endometrioid histology (p=0.02). This difference was seen but not significant in White patients with 98% measurable endometrial stripes in endometrioid cancer and 92% in non-endometrioid cancer (p=0.05). The ability to measure EMS was not different when compared by race alone. The sensitivity of TVUS (EMS of 5mm+) was higher in patients with endometrioid histology (99%) than patients with non-endometrioid histology (94%; p=0.03). Conclusions: In one of the largest and most diverse studies of TVUS performance in endometrial cancer patients to date, TVUS was more effective at visualizing the EMS and had higher sensitivity in patients with endometrioid compared to non-endometrioid endometrial cancers. While performance did not vary by race, the prevalence of non-endometrioid cancers was twice as high among Black compared to White patients. Our findings suggest that TVUS may be less accurate for diagnosing non-endometrioid endometrial cancer, which disproportionately affects Black women.

P53 Immunohistochemistry staining patterns and prognosis significance in 212 cases of non-endometrioid endometrial cancer

ObjectiveTo investigate the immunohistochemistry (IHC) staining pattern and prognostic significance of p53 in non-endometrioid endometrial cancer (non-EEC). MethodsThis study retrospectively included 212 non-EEC patients, with histological types including serous carcinoma (SC), clear cell carcinoma (CCC), mixed carcinoma (MC), undifferentiated carcinoma (UC), and carcinosarcoma (CS). p53 IHC was interpreted as normal/wild-type and abnormal/mutant-type, the latter including overexpression, complete absence, and cytoplasmic staining patterns. Moreover, uncommon p53 subclonal/heterogeneous staining patterns were described. Disease-free survival (DFS) and overall survival (OS) were employed as endpoints to evaluate the prognostic significance of p53. ResultsIn 212 non-EEC cases, 50 (23.6 %) were p53 wild-type, while 162 (76.4 %) displayed abnormal p53 staining. Overexpression was the predominant abnormal p53 staining pattern (122/162), complete absence followed (33/162). All SCs exhibited the mutant p53 staining pattern. The p53 abnormal expression rates in CCC, MC, UC, and CS were 37.5 %, 78.9 %, 35.7 %, and 75.7 %, respectively. Interestingly, of the 12 MC cases with SC components, barring one with p53 subclonal staining, all showed the mutant-type staining. The concordance rate for p53 expression between epithelial and mesenchymal components of CS was 94.3 % (66/70). Kaplan-Meier curves indicated patients with p53 abnormalities had worse DFS compared to those with wild-type p53 (P=0.025). Multivariate Cox regression confirmed that p53 (HR: 2.270, 95 % CI: 1.124–4.586, P=0.022) independently predicted DFS in non-EEC patients, though not for OS. ConclusionsNon-EEC patients with various histological types exhibit different p53 staining patterns. However, abnormal p53 expression, regardless of histological type, implies a poor DFS in non-EEC patients.

Oncological outcomes of minimally invasive surgery in non-endometrioid endometrial Cancer patients with varying prognostic risks: a retrospective cohort study based on the ESGO/ESTRO/ESP 2020 guidelines

BackgroundNon-endometrioid endometrial carcinomas (NEEC) are characterized by their rarity and adverse prognoses. This study evaluates the outcomes of open versus minimally invasive surgery (MIS) in NEEC patients stratified by prognostic risks according to the 2020 ESGO-ESTRO-ESP risk classification guidelines.MethodsA retrospective analysis was performed on 99 NEEC patients who underwent initial surgery at Fujian University Cancer Hospital. Patients were categorized into two groups: those undergoing MIS and those undergoing open surgery. We compared disease-free survival (DFS) and overall survival (OS) between these groups. Cox regression analysis was employed to identify risk factors for DFS, which were further validated via bootstrap statistical methods.ResultsThe study included 31 patients in the MIS group and 68 in the open surgery group. The demographics and clinical characteristics such as age, body mass index, comorbidities, histological subtypes, and FIGO stage were similar between groups (P > 0.05). The MIS group experienced ten recurrences (1 vaginal, 2 lymph nodes, 7 distant metastases), whereas the open surgery group had seven recurrences (1 vaginal, 3 lymph nodes, 1 pelvis, 2 distant metastases), yielding recurrence rates of 10.3% versus 25.6% (P = 0.007). Besides lymphovascular space invasion (LVSI), surgical approach was also identified as an independent prognostic factor for DFS in high-risk patients (P = 0.037, 95% CI: 1.062–7.409). The constructed nomogram demonstrated a robust predictive capability with an area under the curve (AUC) of 0.767. Survival analysis for high- and intermediate-risk patients showed no significant differences in OS between the two groups (Phigh risk = 0.275; Pintermediate−risk = 0.201). However, high-risk patients in the MIS group exhibited significantly worse DFS (P = 0.001).ConclusionThis investigation is the inaugural study to assess the impact of surgical approaches on NEEC patients within the framework of the latest ESGO-ESTRO-ESP risk classifications. Although MIS may offer clinical advantages, it should be approached with caution in high-risk NEEC patients due to associated poorer DFS outcomes.

Unravelling the molecular landscape of endometrial cancer subtypes: insights from multiomics analysis.

Endometrial cancer (EC) as one of the most common gynecologic malignancies is increasing in incidence during the past 10 years. Genome-Wide Association Studies (GWAS) extended to metabolic and protein phenotypes inspired us to employ multiomics methods to analyze the causal relationships of plasma metabolites and proteins with EC to advance our understanding of EC biology and pave the way for more targeted approaches to its diagnosis and treatment by comparing the molecular profiles of different EC subtypes. Two-sample mendelian randomization (MR) was performed to investigate the effects of plasma metabolites and proteins on risks of different subtypes of EC (endometrioid and nonendometrioid). Pathway analysis, transcriptomic analysis, and network analysis were further employed to illustrate gene-protein-metabolites interactions underlying the pathogenesis of distinct EC histological types. The authors identified 66 causal relationships between plasma metabolites and endometrioid EC, and 132 causal relationships between plasma proteins and endometrioid EC. Additionally, 40 causal relationships between plasma metabolites and nonendometrioid EC, and 125 causal relationships between plasma proteins and nonendometrioid EC were observed. Substantial differences were observed between endometrioid and nonendometrioid histological types of EC at both the metabolite and protein levels. The authors identified seven overlapping proteins (RGMA, NRXN2, EVA1C, SLC14A1, SLC6A14, SCUBE1, FGF8) in endometrioid subtype and six overlapping proteins (IL32, GRB7, L1CAM, CCL25, GGT2, PSG5) in nonendometrioid subtype and conducted network analysis of above proteins and metabolites to identify coregulated nodes. Our findings observed substantial differences between endometrioid and nonendometrioid EC at the metabolite and protein levels, providing novel insights into gene-protein-metabolites interactions that could influence future EC treatments.

Comparison of survival and complications between minimally invasive and open staging surgeries in non-endometrioid endometrial cancer

ObjectiveThis study aimed to compare survival and complications between minimally invasive surgery and open surgery and evaluate related risk factors in patients with non-endometrioid endometrial cancer. MethodsClinicopathologic characteristics; survival outcomes; complications; and prognostic factors associated with progression-free survival and overall survival were compared among patients with non-endometrioid endometrial cancer who underwent primary staging surgery using laparoscopic, robotic, or open abdominal surgery (2004–2017). ResultsIn total, 91 patients were included: 41 and 50 underwent minimally invasive surgery and open surgery, respectively. The minimally invasive surgery and open surgery groups showed similar progression-free survival (5-year progression-free survival rate, 58.7 % vs. 58.5 %; P = .925) and overall survival (5-year overall survival rate, 73.6 % vs. 80.3 %; P = .834). Intraoperative (7.2 % vs. 6.0 %; P = .111) and postoperative surgical complications (14.6 % vs. 26.0 %; P = .165) were similar between the groups. However, blood loss was lower (mean, 305.1 vs. 561.2 ml, P < .001) and hospital stay was shorter (mean, 8.2 vs. 15.4 days, P < .001) in the minimally invasive surgery group. Using multivariate analysis, lymphovascular space invasion was identified as poor prognostic factor for progression-free survival (adjusted hazard ratio [HR], 3.054; 95 % confidence interval [CI], 1.521–6.132; P = .002) and overall survival (adjusted HR, 3.918; 95 % CI, 1.455–10.551; P = .007), whereas age ≥ 60 years was poor prognostic factor for only overall survival (adjusted HR, 5.0953; 95 % CI, 1.660–15.378; P = .004). ConclusionsSurgical outcomes did not differ between the minimally invasive and open surgery group in patients with non-endometrioid endometrial cancer. Lymphovascular space invasion was a significant survival factor in this context.

Endometrial cancer survival in populations of African descent.

To examine whether the endometrial cancer (EC) survival disadvantage among Black populations is US-specific, a comparison between African-descent populations from different countries with a high development index is warranted. We analyzed 28 213 EC cases from cancer registries in Florida (2005-2018) and the French Caribbean islands of Martinique (2005-2018) and Guadeloupe (2008-2018) combined. Kaplan-Meier and all-cause Cox proportional hazards models were used to compare survival. Models were stratified by EC histology type and the main predictor examined was race/ethnicity (non-Hispanic White [NHW] and no-Hispanic Black [NHB] women in the United States versus Black women residing in the Caribbean). For endometrioid and nonendometrioid EC, after adjusting for age, histology, stage at diagnosis, receipt of surgery, period of diagnosis, and poverty level, US NHB women and Caribbean Black women had a higher risk of death relative to US NHW women. There was no difference between US NHB and Caribbean Black women (hazard ratio [HR] = 1.07; 95% CI, 0.88-1.30) with endometrioid EC. However, Caribbean Black women with nonendometrioid carcinomas had a 40% higher risk of death (HR = 1.40; 95% CI, 1.13-1.74) than US NHB women. The low EC survival among US Black women extends to foreign populations of African descent. For the aggressive nonendometrioid ECs, survival among Caribbean Black women outside of the United States is considerably worse. This article is part of a Special Collection on Gynecological Cancers.

Predicting the Risk of nOdal disease with histological and Molecular features in Endometrial cancer: the prospective PROME trial

ObjectiveTo assess the role of histopathological and molecular features in predicting the risk of nodal metastases in apparent early-stage endometrial cancer patients undergoing sentinel node mapping.MethodsThis is a prospective trial....

Development and external validation of a nomogram for predicting overall survival of patients with non-endometrioid endometrial cancer: A population-based analysis

ObjectivesThe main objective of this study was to identify the key predictors and construct a nomogram that can be used to predict the overall survival of individuals with non-endometrioid endometrial cancer. MethodsA total of 2686 non-endometrioid endometrial cancer patients confirmed between 1988 and 2018 were selected from the Surveillance, Epidemiology, and End Results database. They were divided into a training cohort and an internal validation cohort. Independent risk factors were chosen by Cox regression analyses. A predictive nomogram model for overall survival was constructed based on above factors. A Chinese cohort of 41 patients was collected to be an external validation cohort. ResultsEight variables were estimated as independent predictors for overall survival. A nomogram was established using these factors. The C-index for predicting the overall survival of patients with non-endometrioid endometrial cancer from the nomogram was 0.734, 0.700, and 0.767 in training, internal, and external validation cohort, respectively. Calibration plots and decision curve analysis showed that the nomogram was valuable for further clinical application. ConclusionWe constructed a nomogram which can be used as an effective tool to predict the 3- and 5-year overall survival of Non-endometrioid endometrial cancer patients.

Determination of p53abn endometrial cancer: a multitask analysis using radiological-clinical nomogram on MRI.

We aimed to differentiate endometrial cancer (EC) between TP53mutation (P53abn) and Non-P53abn subtypes using radiological-clinical nomogram on EC body volume MRI. We retrospectively recruited 227 patients with pathologically proven EC from our institution. All these patients have undergone molecular pathology diagnosis based on the Cancer Genome Atlas. Clinical characteristics and histological diagnosis were recorded from the hospital information system. Radiomics features were extracted from online Pyradiomics processors. The diagnostic performance across different acquisition protocols was calculated and compared. The radiological-clinical nomogram was established to determine the nonendometrioid, high-risk, and P53abn EC group. The best MRI sequence for differentiation P53abn from the non-P53abn group was contrast-enhanced T1WI (test AUC: 0.8). The best MRI sequence both for differentiation endometrioid cancer from nonendometrioid cancer and high-risk from low- and intermediate-risk groups was apparent diffusion coefficient map (test AUC: 0.665 and 0.690). For all 3 tasks, the combined model incorporating all the best discriminative features from each sequence yielded the best performance. The combined model achieved an AUC of 0.845 in the testing cohorts for P53abn cancer identification. The MR-based radiomics diagnostic model performed better than the clinical-based model in determining P53abn EC (AUC: 0.834 vs 0.682). In the present study, the diagnostic model based on the combination of both radiomics and clinical features yielded a higher performance in differentiating nonendometrioid and P53abn cancer from other EC molecular subgroups, which might help design a tailed treatment, especially for patients with high-risk EC. (1) The contrast-enhanced T1WI was the best MRI sequence for differentiation P53abn from the non-P53abn group (test AUC: 0.8). (2) The radiomics-based diagnostic model performed better than the clinical-based model in determining P53abn EC (AUC: 0.834 vs 0.682). (3) The proposed model derived from multi-parametric MRI images achieved a higher accuracy in P53abn EC identification (AUC: 0.845).

Risk factors for pelvic and para-aortic lymph node metastasis in non-endometrioid endometrial cancer

PurposeThe aim of this study was to evaluate the risk factors for pelvic lymph node metastasis (LNM) and para-aortic LNM in non-endometrioid endometrial cancer (non-EEC). MethodsA total of 283 patients with non-EEC hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2012 to December 2020 were included. Various characteristics were retrospectively analyzed in relation to LNM. ResultsUnivariable and multivariable logistic regression analysis revealed cervical stromal invasion (OR = 3.441, 95% CI = 1.558–7.6, p = 0.002), myometrial invasion ≥1/2 (OR = 2.661, 95% CI = 1.327–5.337, p < 0.006), lymphovascular space involvement (LVSI) (OR = 4.118, 95% CI = 1.919–8.837, p < 0.001), positive peritoneal cytology (OR = 2.962, 95% CI = 1.344–6.530, p = 0.007), CA125 (OR = 1.002, 95% CI = 1–1.004, p = 0.026) were the independent risk factors for pelvic LNM. And myometrial invasion ≥1/2 (OR = 5.881, 95% CI = 2.056–16.427, p = 0.001), LVSI (OR = 4.962, 95% CI = 1.933–12.740, p = 0.001), adnexal (OR = 5.921, 95% CI = 2.003–17.502, p = 0.001) were the independent risk factors for para-aortic LNM. With the increase of independent risk factors, the rates of LNM were increased significantly. ConclusionsCervical stromal invasion, myometrial invasion ≥1/2, LVSI, positive peritoneal cytology, and CA125 were risk factors for pelvic LNM. Myometrial invasion ≥1/2, LVSI and involvement of the adnexa were risk factors for para-aortic LNM which could provide a good basis to help predict which non-EEC patients are at higher risk for LNM.

Prognostic evaluation of lymph-vascular space invasion in patients with endometrioid and non-endometrioid endometrial cancer: A multicenter study

IntroductionThe prognostic value of lymph-vascular space invasion (LVSI) on endometrial cancer (EC) remains controversial. This study aimed to explore the impact of LVSI on patients with endometrioid and non-endometrioid EC in China. Materials and methodsWe analyzed EC patients who underwent surgery from 2010 to 2019 in seven Chinese hospitals retrospectively and stratified patients based on histopathologic types and LVSI status. Endpoints were disease-free survival (DFS) and overall survival (OS). Propensity score matching (PSM) algorithm was used to balance the confounding factors. The survival was examined using Kaplan-Meier analysis. Cox proportional hazards regression analyses were used to find prognostic independent risk factors. ResultsAmong 3715 EC patients, LVSI positive rate was 9.31% (346/3715). After matching, LVSI present group had shorter DFS (P = 0.005), and similar OS (P = 0.656) than LVSI absent group for endometrioid EC patients. For non-endometrioid EC patients, there was no statistical difference in either DFS (P = 0.536) or OS (P = 0.512) after matching. The multivariate Cox analysis showed that LVSI was an independent risk factor of DFS [hazard ratio (HR) 2.62, 95% confidence intervals (CI) 1.35–5.10, P = 0.005] and not OS (HR 1.24, 95%CI 0.49–3.13, P = 0.656) for endometrioid EC patients. It was not a prognostic factor of either DFS (HR 1.28, 95%CI 0.58–2.81, P = 0.539) or OS (HR 1.33, 95%CI 0.55–3.13, P = 0.515) for non-endometrioid EC patients. ConclusionLVSI is an adverse prognostic factor for endometrioid EC patients and has no impact on non-endometrioid EC patients. Necessity of postoperative adjuvant therapy based on LVSI needs to be carefully considered for non-endometrioid EC patients.

The causal effects of genetically predicted alcohol consumption on endometrial cancer risk from a Mendelian randomization study

Endometrial cancer (EC) is a common gynecological tumor in females with an increasing incidence over the past few decades. Alcohol consumption has been linked to the occurrence of various cancers; However, epidemiological studies have shown inconsistent associations between alcohol consumption and EC risk. In order to avoid the influence of potential confounding factors and reverse causality in traditional epidemiological studies, we used a method based on genetic principles-Mendelian randomization (MR) analysis to test whether there is a causal relationship between alcohol consumption and EC. MR analysis was conducted using publicly available summary-level data from genome-wide association studies (GWAS). Fifty-seven single nucleotide polymorphisms (SNPs) were extracted as instrumental variables for alcohol exposure from the GWAS and Sequencing Consortium of Alcohol and Nicotine GWAS summary data involving 941,287 participants of European ancestry. SNPs for EC were obtained from the Endometrial Cancer Association Consortium, the Endometrial Cancer Epidemiology Consortium, and the UK Biobank, involving 121,885 European participants. The inverse variance weighted (IVW) method was used as the primary method to estimate the causal effect, and the MR-Egger regression and weighted median method were used as supplementary methods. Sensitivity analyses were conducted using the Mendelian Randomization Pleiotropy RESidual Sum and Outlier global test, MR-Egger intercept test, and leave-one-out analysis to evaluate the impact of pleiotropy on causal estimates. An increase of 1 standard deviation of genetically predicted log-transformed alcoholic drinks per day was associated with a 43% reduction in EC risk [odds ratio (OR) = 0.57, 95% confidence interval (CI) 0.41–0.79, P < 0.001]. Subgroup analysis of EC revealed that alcohol consumption was a protective factor for endometrioid endometrial cancer (EEC) (OR = 0.56, 95% CI 0.38–0.83, P = 0.004) but not for non-endometrioid endometrial cancer (NEC) (OR = 1.36, 95% CI 0.40–4.66, P = 0.626). The MR-Egger regression and weighted median method yielded consistent causal effects with the IVW method. The consistent results of sensitivity analyses indicated the reliability of our causal estimates. Additionally, alcohol consumption was associated with decreased human chorionic gonadotropin (HCG) and insulin-like growth factor 1 (IGF1) levels. This MR study suggests that genetically predicted alcohol consumption is a protective factor for EC, particularly for EEC, and this protective effect may be mediated through the reduction of HCG and IGF1.

The Impact of Waiting Time-to-Surgery on Survival in Endometrial Cancer Patients.

Endometrial cancer (EC) is the most common gynecological cancer in developed countries and a standard treatment of surgery should be performed as expediently as possible. Delay time to surgery and survival was debated. The aim of this investigation was to evaluate the effect of time-interval between diagnosis and surgery (TDS) in EC patients with regards to prognosis and mortality rates. This retrospective study was conducted between January 2009 and May 2021 at Bhumibol Adulyadej Hospital, Thailand. Subjects were EC cases who underwent primary surgery during the study period. Cases with partial treatment were disqualified from the study. Subjects who underwent surgery before and after 6 weeks were classified as early and delayed surgery groups. Baseline and clinical characteristics were collected and analyzed. During the study period, 419 EC cases were recruited. The mean age of participants was 56.8 years. Two-thirds (338/491) of subjects were menopausal. Endometrioid histology (406/491) was the most common histology subtype. Five years disease free survival (DFS) of early and delayed surgery groups were comparable at a percentage of 82.5 and 83.0, respectively. Among advanced stage and non-endometrioid EC cases, the delayed surgery group had significantly shorter DFS than the early group. Advanced stage, high grade and positive lympho-vascular space invasion (LVSI) were independent factors for poor DFS. Predictive factors for mortality were advanced stage and tumor recurrence. The TDS was not a prognostic factor for disease recurrence or overall mortality. Time to surgery equal to or more than 6 weeks gave worse prognosis for DFS among advanced stage or non-endometrioid histology EC.

Impact of COVID-19 Pandemic on the Diagnostic and Therapeutic Management of Endometrial Cancer: A Monocentric Retrospective Comparative Study.

Endometrial cancer represents an ideal target to evaluate the impact of COVID-19 being the most frequent gynecological malignancy in Italy, generally detected at early stages and correlated with favorable oncological outcomes. The present comparative retrospective study carried out at Campus Bio-medico University Foundation in Rome aims to evaluate the impact of the COVID-19 pandemic on the presentation, diagnosis and treatment of EC. All women with a histological diagnosis of non-endometrioid and endometrioid endometrial cancer between 1 March 2018 and 31 October 2022 were included. The number of cases was higher in period 2 (95 vs. 64 cases). Time to diagnosis did not show statistically significant differences but in period 2, 92.06% of the diagnoses were made following abnormal uterine bleeding, while in period 1, only 67.02% were. The waiting time for the intervention was significantly shorter in period 2. Definitive histology, FIGO staging, surgical technique and adjuvant therapy did not show significant differences between the two periods. The study demonstrates that the impact of the COVID-19 pandemic did not have a direct effect on the diagnostic delay, tumor staging and type of therapy but rather on the presentation pattern of endometrial cancer.

Prognostic significance of omental disease and the role of omentectomy in non-endometrioid endometrial cancer.

Non-endometrioid endometrial cancers (non-EEC) have different management from endometrioid endometrial cancers. The purpose of this study was to investigate the prognostic significance of omental disease and the role of omentectomy in non-endometrioid endometrial cancer and discuss the current literature with the findings. The study included two hundred-three patients with non-EEC who underwent surgical treatment and follow-up between January 1996 and December 2018 in a University Hospital Gynecologic Oncology Center. The patients were divided into three groups according to whether omentectomy was performed and the presence of omental metastasis. The patient's demographics, clinical characteristics such as stage, grade, histopathologic type, lymphovascular space invasion (LVSI), myometrial invasion, lymph node involvement, and survival outcomes were compared between the groups. The study included 203 patients. Twenty-five patients (12%) had omental metastases. LVSI was reported in 57.3%, 88.0%, and 43.2% of the non-omentectomy, no-omental metastasis, and omental metastatic groups, respectively (p = 0.001). The 5-year disease-free survival (DFS) and overall survival (OS) rates according to the tumor grade, peritoneal cytology, and lymphadenectomy were also compared and were found to be statistically similar. The five-year OS rates were 70.6% for the group without omental metastases and 16.2% for the group with omental metastases, respectively (p = 0.001). In the group of omentectomy, the five-year DFS rates were 62.2% in cases without omental metastasis and 13.0% in cases with omental metastasis (p = 0.001). The five-year OS rates of 86.3% and DFS rates of 80.0% in the group without omentectomy. In non-endometrioid tumors, the survival rate was better in the group that did not undergo omentectomy. Based on these results, we can say that omentectomy may not be necessary for non-endometrioid tumors whose omentum is found to be normal in intraoperative visual examination.

Prognosis and adjuvant chemotherapy for patients with malignant peritoneal cytology in early-stage non-endometrioid endometrial cancer

ObjectiveTo investigate the influence of malignant peritoneal cytology (MPC) on the prognosis of early-stage patients with endometrial clear cell carcinoma(CCC) and serous carcinoma(SC), and the value of chemotherapy in their treatment. MethodsA retrospective observational cohort study was conducted by querying the National Cancer Institute's Surveillance, Epidemiology, and End Results Program from 2010 to 2019. Women with early-stage CCC and SC with available peritoneal cytology results were enrolled. Propensity score matching(PSM) and propensity score inverse probability of treatment weighting (IPTW) was used to balance the measured covariates in each sub-cohort. ResultsA total of 3,616 eligible patients were included, and 368 patients had MPC (10.2%). Women with MPC were more likely to receive postoperative chemotherapy (OR 2.033; 95%CI 1.589–2.602). In PSM model, MPC had worse overall survival(OS) and cancer-specific survival (CSS) (All,p < 0.001). The 5-year OS rates were 56.5% for women with MPC and 74.4% for those with negative peritoneal cytology, and the 5-year CSS rates were 60.8% versus 80.0%(All, p < 0.0001). In the subgroup analyses, MPC was associated with decreased OS and CSS in serous, clear cell histology group, and stage IA cases(All,p < 0.001), but not for stage IB or stage II disease. In multivariate analysis, chemotherapy improved the prognosis of patients with MPC(OS:p = 0.005; CSS:p = 0.010). Additionally, in stage IA subgroup, chemotherapy improved survival outcomes in patients with MPC(OS:P = 0.025; CSS:P = 0.038), in NPC patients, however, chemotherapy was a good prognostic factor for OS (P = 0.001) but not for CSS(P = 0.300). ConclusionMPC was a prognostic factor for decreased survival in early-stage endometrial CCC and SC, and those with MPC could further benefit from chemotherapy.

Dopamine receptors D1 and D2 show prognostic significance and potential therapeutic applications for endometrial cancer patients

ObjectiveCatecholaminergic signaling has been a target for therapy in different type of cancers. In this work, we characterized the ADRβ2, DRD1 and DRD2 expression in healthy tissue and endometrial tumors to evaluate their prognostic significance in endometrial cancer (EC), unraveling their possible application as an antitumor therapy. Methods109 EC patients were included. The expression of the ADRβ2, DRD1 and DRD2 proteins was evaluated by immunohistochemistry and univariate and multivariate analysis to assess their association with clinic-pathological and outcome variables. Finally, HEC1A and AN3CA EC cell lines were exposed to different concentrations of selective dopaminergic agents alone or in combination to study their effects on cellular viability. ResultsADRβ2 protein expression was not associated with clinico-pathological parameters or prognosis. DRD1 protein expression was reduced in tumors samples but showed a significant inverse association with tumor size and stage. DRD2 protein expression was significantly associated with non-endometrioid EC, high grade tumors, tumor size, worse disease-free survival (HR = 3.47 (95%CI:1.35–8.88)) and overall survival (HR = 2.98 (95%CI:1.40–6.34)). The DRD1 agonist fenoldopam showed a reduction of cellular viability in HEC1A and AN3CA cells. The exposure to domperidone, a DRD2 antagonist, significantly reduced cell viability compared to the control. Finally, DRD1 agonism and DRD2 antagonism combination induced a significant reduction in cell viability of the AN3CA cells compared to monotherapy, close to being an additive response than a synergistic effect (CI of 1.1 at 0.5% Fa). ConclusionDRD1 and DRD2 expression levels showed a significant association with clinico-pathological parameters. Both the combined activation of DRD1 and blockage of DRD2 may form an innovative strategy to inhibit tumor growth in EC.

Endometrial cancer risk and trends among distinct African descent populations.

Endometrial cancer (EC) is the fourth most common cancer among Black women in the United States, a population disproportionately affected by aggressive nonendometrioid subtypes (e.g., serous, carcinosarcoma). To examine EC vulnerability among a wider spectrum of African descent populations, a comparison between Black women residing in different countries, rather than in the United States alone, is needed. The authors analyzed 34,789 EC cases from Florida (FL) (2005-2018), Martinique (2005-2018), and Guadeloupe (2008-2018) based on cancer registry data. Age-adjusted incidence rates, incidence rate ratios (IRRs), and annual percent changes (APC) in trends were estimated for Black populations residing in the United States (non-Hispanic Blacks [NHB]) and Caribbean. The US non-Hispanic White (NHW) population was used as a reference. Caribbean Black women had the lowest rates for endometrioid and nonendometrioid subtypes. Nonendometrioid types were most common among US (FL) NHBs (9.2 per 100,000), 2.6 times greater than NHWs (IRR, 2.60; 95% confidence interval [CI], 2.44-2.76). For endometrioid EC, rates increased 1.8% (95% CI, 0.1-3.5) yearly from 2005 to 2018 for US (FL) NHBs and 1.2% (95% CI, 0.9-1.6) for US (FL) NHWs whereas no change was observed for Caribbean Blacks. For nonendometroid carcinomas, rates increased 5.6% (95% CI, 4.0-7.2) among US (FL) NHB, 4.4% (95% CI, 0.3-8.6) for Caribbean Black, and 3.9% for US (FL) NHW women (95% CI, 2.4-5.5). Lower rates of nonendometrioid EC among Caribbean Black women suggest that vulnerability for these aggressive tumor subtypes may not currently be an overarching African ancestry disparity. Most importantly, there is an alarmingly increasing trend in nonendometrioid across all populations studied, which warrants further surveillance and etiological research for this particular subtype. We analyze population-based incidence rates and trends of endometrial cancer (EC) for African descent populations residing in different countries (i.e., United States, Martinique, Guadeloupe) to examine whether EC vulnerability among Black women is socio-environmental or more ancestry-specific in nature. The increased EC risk was not uniform across all Black women since the Caribbean had the lowest rates (for endometrioid and nonendometrioid histology subtypes). Regardless, from 2005 to 2018, there was an increasing trajectory of nonendometrioid EC for all groups, regardless of race.

Non-endometrioid endometrial cancer: analysis of recurrence pattern and identification of prognostic and treatment factors affecting recurrence and survival.

We investigated the characteristics of recurrence pattern and survival of patients with non-endometrioid endometrial cancer (NEEC) and attempted to identify prognostic and treatment factors affecting disease-free survival (DFS) and overall survival (OS) of these patients. Fifty-seven patients with histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) stage IA-IVA NEEC from February 2003 to December 2021 were retrospectively analyzed. The 5‑year DFS and OS rates of the total cohort were 50.6% and 56.1%, respectively. Recurrence occurred in 28patients (49.1%) during follow-up, and the most common recurrence pattern was distant metastasis (DM; 78.6% of total recurrences). The occurrence of relapse significantly reduced 5‑year OS (recurrence group vs. non-recurrence group: 12.5% vs. 100%; p < 0.001). In univariate analysis, adjuvant radiotherapy (RT) group showed significantly higher 5‑year DFS (56.7% vs. 37.9%; p = 0.04), local recurrence-free survival (91.6% vs. 50.5%; p = 0.01), and regional recurrence-free survival (88.2% vs. 56.5%; p < 0.01) than the non-RT group. In multivariate analysis, advanced FIGO stage was identified as anegative prognostic factor for DFS and OS. Lymphovascular space invasion (LVSI) and adjuvant RT were independent prognostic factors for DFS. The most common recurrence pattern observed in patients with NEEC was DM. FIGO stage and LVSI were identified as prognostic factors for survival, and RT was identified as atherapeutic modality that could increase DFS. To improve the OS of patients with NEEC, the addition of effective chemotherapy that can reduce DM may be important.

Evolving treatment landscape of advanced endometrial cancer – A current perspective from a German tertiary referral center for gynecological oncology

Endometrial cancer (EC) represents the most prevalent cancer of the female genital tract worldwide. Although EC has an overall good prognosis compared to other gynecological malignancies, a recent report from the American Cancer Society indicated that the cancer-specific survival of patients with EC has decreased since the 1970s, while the incidence has remained stable ( [1] Siegel R.L. Miller K.D. Fuchs H.E. Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022 Jan; 72: 7-33 Google Scholar ). The increasing EC-specific mortality is particularly attributable to EC with non-endometrioid histology. Although non-endometrioid histology represents only about 20% of all EC, non-endometrioid EC account for more than half of EC-related deaths ( 2 Clarke M.A. Devesa S.S. Harvey S.V. Wentzensen N. Hysterectomy-Corrected Uterine Corpus Cancer Incidence Trends and Differences in Relative Survival Reveal Racial Disparities and Rising Rates of Nonendometrioid Cancers. J Clin Oncol Off J Am Soc Clin Oncol. 2019 Aug 1; 37: 1895-1908 Google Scholar , 3 McGunigal M. Liu J. Kalir T. Chadha M. Gupta V. Survival Differences Among Uterine Papillary Serous, Clear Cell and Grade 3 Endometrioid Adenocarcinoma Endometrial Cancers: A National Cancer Database Analysis. Int J Gynecol Cancer Off J Int Gynecol Cancer Soc. 2017 Jan; 27: 85-92 Google Scholar ). The determinants underlying the increase in non-endometrioid EC remain elusive. Overall, EC contrasts to the majority of other malignancies, whose cancer-specific survival has improved in recent years ( [1] Siegel R.L. Miller K.D. Fuchs H.E. Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022 Jan; 72: 7-33 Google Scholar ). Hence, it is crucial to reconsider and optimize existing therapy strategies and, to incorporate novel scientific findings into therapy algorithms. Here, we compile existing therapeutic concepts for advanced EC and propose a treatment algorithm based on current clinical and translational research findings.