Management Of Endometrial Cancer Research Articles

Lymph node metastasis probability in young patients eligible for conservative management of endometrial cancer

ObjectiveEndometrial cancer (EC) is a rare condition in young women. The objective of this study was to evaluate the risk of pelvic lymph node (LN) metastasis in young women with EC who are candidates for conservative management. MethodsUsing the SEER database, a population-based analysis was conducted to identify women <45 years with grade 1, 2, or 3 endometrioid adenocarcinoma stage IA (FIGO 2009) who underwent pelvic lymphadenectomy with at least ten LNs removed. The LN macrometastases rate based on conventional histological diagnosis was analyzed according to tumor grade and myometrial invasion (MI) on final histology. ResultsA cohort of 1284 women was analyzed. The LN metastasis rates were: 2/414 (0.5%) grade 1 EC without MI, 5/239 (2.1%) grade 2 or 3 EC without MI, 5/308 (1.6%) grade 1 EC with MI, and 14/323 (4.3%) grade 2 or 3 EC with MI. Tumor size was not correlated with LN metastasis probability. ConclusionsYoung patients eligible for conservative management have a low rate of LN macrometastasis, especially in stage IA without MI grade 1 EC. A systematic lymphadenectomy should not be performed in these patients. Prospective study evaluating the sentinel LN mapping in conservative management of EC could be performed to assess the LN micrometastasis rate.

Patient perceptions and understanding of obesity related endometrial cancer

Obesity is the greatest risk factor for endometrial cancer. There is often a lack of recognition amongst patients about this risk. Evidence for weight-loss in the management of endometrial cancer is emerging. This was questionnaire-based study, that examined opinions and attitudes of patients with endometrial cancer and obesity towards obesity as a risk factor for cancer as well as examining their willingness to engage in weight loss interventions as an alternative treatment to endometrial cancer. This survey was conducted in a gynaeoncology out-patient department in Ireland. A total of 45/50 (90%) of questionnaires were completed. The majority of the patients questioned (86.7%; 39/45) agreed that obesity is a disease. Just over half of the cohort (53.3%; 24/45) believed that obesity can cause cancer. Over one-third, 39.9% (18/45) either disagreed or strongly disagreed that obesity is a risk factor for endometrial cancer while 35.5% (16/45) agreed or strongly agreed. Two-thirds (66.6%; 30/45) knew that the greatest amount of weight could be lost through metabolic surgery. Over three-quarters (82.1%; 37/45) of patients surveyed would be willing to engage in a combination of treatments in order to achieve weight-loss should it be proven to have a role in the management of endometrial cancer. This study demonstrates a need for patient education regarding the strong relationship between obesity and endometrial cancer risk. Patients are willing to consider weight loss interventions if they were proven to be as safe and effective as pelvic surgery in the management of endometrial cancer.

Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway

BackgroundPyroptosis belongs to a novel inflammatory programmed cell death pathway, with the possible prognosis of endometrial cancer related to the terminal protein GSDMD. Hydrogen exerts a biphasic effect on cancer by promoting tumor cell death and protecting normal cells, which might initiate GSDMD pathway-mediated pyroptosis.MethodsWe performed immunohistochemical staining and western immunoblotting analysis to observe expression of NLRP3, caspase-1, and GSDMD in human and xenograft mice endometrial cancer tissue and cell lines. We investigated treatment with hydrogen could boost ROS accumulation in endometrial cancer cells by intracellular and mitochondrial sources. GSDMD shRNA lentivirus was used to transfect endometrial cancer cells to investigate the function of GSDMD protein in pyroptosis. Propidium iodide (PI) staining, TUNEL assay, measurement of lactate dehydrogenase (LDH) release and IL-1β ELISA were used to analysis pyroptosis between hydrogen-supplemented or normal culture medium. We conducted in vivo human endometrial tumor xenograft mice model to observe anti-tumor effect in hydrogen supplementation.ResultsWe observed overexpression of NLRP3, caspase-1, and GSDMD in human endometrial cancer and cell lines by IHC and western immunoblotting. Hydrogen pretreatment upregulated ROS and the expression of pyroptosis-related proteins, and increased the number of PI- and TUNEL-positive cells, as well as the release of LDH and IL-1β, however, GSDMD depletion reduced their release. We further demonstrated that hydrogen supplementation in mice was sufficient for the anti-tumor effect to inhibit xenograft volume and weight of endometrial tumors, as mice subjected to hydrogen-rich water displayed decreased radiance. Tumor tissue sections in the HRW groups presented moderate-to-strong positive expression of NLRP3, caspase-1 and GSDMD. Hydrogen attenuated tumor volume and weight in a xenograft mouse model though the pyroptotic pathway.ConclusionsThis study extended our original analysis of the ability of hydrogen to stimulate NLRP3 inflammasome/GSDMD activation in pyroptosis and revealed possible mechanism (s) for improvement of anti-tumor effects in the clinical management of endometrial cancer.

LAMC1 is a prognostic factor and a potential therapeutic target in endometrial cancer.

ObjectiveWith the emerging significance of genetic profiles in the management of endometrial cancer, the identification of tumor-driving genes with prognostic value is a pressing need. The LAMC1 gene, encoding the laminin subunit gamma 1 (LAMC1) protein, has been reported to be involved in the progression of various malignant tumors. In this study, we aimed to investigate the role of LAMC1 in endometrial cancer and elucidate the underlying mechanism.MethodsWe evaluated the immunohistochemical expression of LAMC1 in atypical endometrial hyperplasia and endometrial cancer. Within the endometrial cancer cases, we analyzed the association of LAMC1 overexpression with clinicopathological factors and prognosis. Furthermore, to indentify genes influenced by LAMC1 overexpression, we transfected HEC50B and SPAC-S cells with siRNA targeting LAMC1 and conducted microarray gene expression assays.ResultsWhile none of the atypical endometrial hyperplasia specimens exhibited LAMC1 overexpression, endometrial cancer possessed a significantly higher LAMC1 overexpression rate. LAMC1 overexpression was strongly associated with histological type, lymphovascular space invasion, lymph node metastasis, advanced International Federation of Gynecology and Obstetrics stage, and poor overall survival in endometrial cancer. Gene expression microarray analysis identified 8 genes correlated with tumor progression (LZTFL1, TAPT1, SEL1L, PAQR6, NME7, TMEM109, CCDC58, and ANKRD40) that were commonly influenced in HEC50B and SPAC-S by LAMC1 silencing.ConclusionLAMC1 overexpression is a potent biomarker for identifying endometrial cancer patients needing aggressive adjuvant therapy. We elucidated 8 candidate genes that may mediate progression of LAMC1 overexpressing cancer. Further investigation of the underlying mechanism should lead to the discovery of new therapeutic targets.

Detecting Endometrial Cancer by Blood Spectroscopy: A Diagnostic Cross-Sectional Study

Background: Endometrial cancer is the sixth most common cancer in women with a rising incidence worldwide. Current approaches for the diagnosis and screening of endometrial cancer are invasive, expensive and of moderate diagnostic accuracy, limiting their clinical utility. There is a need for cost-effective and minimally invasive biomarkers to facilitate the early detection and timely management of endometrial cancer. Methods: We analysed blood plasma samples in a cross-sectional diagnostic accuracy study of women with endometrial cancer(n=342), its precursor lesion atypical hyperplasia(n=68) and healthy controls(n=242, total n=652) using attenuated total reflection-Fourier transform infrared(ATR-FTIR) spectroscopy and machine learning algorithms. Findings : We show that blood-based infrared spectroscopy has the potential to detect endometrial cancer with 87% sensitivity and 78% specificity. Its accuracy is highest for type I endometrial cancer, the most common subtype, and for atypical hyperplasia, with sensitivities of 91% and 100%, and specificities of 81% and 88%, respectively. Interpretation: Our large-cohort study shows that a simple blood test could enable the early detection of endometrial cancer of all stages in symptomatic women and provide the basis of a screening tool in high-risk groups. Such a test will not only differentially diagnose endometrial cancer but also detect its precursor lesion atypical hyperplasia, the early recognition of which may allow fertility-sparing management and cancer prevention. Funding Statement: The authors were supported by the Rosemere Cancer Foundation, CAPES–Brazil, Wellcome Trust, Wellbeing of Women, MRC, NIHR and the Department of Health. The views expressed are those of the authors and not necessarily of the funders. Declaration of Interests: The authors declare no potential conflicts of interest. Ethics Approval Statement: All women gave written, informed consent to participate and donated their clinical data and blood samples for future research. Ethical approval was obtained as follows: Weight loss study (North West Research Ethics Committee ref. 12/NW/0050), PROTEC study (Cambridge East Research Ethics Committee ref. 15/EE/0063), PREMIUM study (North West Research Ethics Committee ref. 14/NW/1236), Metformin study (North West Research Ethics Committee ref. 11/NW/0442), PETALS study (NRES Committee North West – Lancaster ref. 15/NW/0733), DETECT study (North West Research Ethics Committee - Greater Manchester 16/NW/0660), and East of England – Cambridge Central Research Ethics Committee ref. 16/EE/0010.

Comparative Study of Laparoscopic versus Conventional Open Surgical Staging Procedure for Endometrial Cancer: Our Institutional Experience.

Objective:The aim of this study was to compare laparoscopic surgical staging of endometrial cancer with conventional open methods.Materials and Methods:The retrospective data were collected from 90 endometrial cancer patients who were operated between 2013 and 2018 in our government institution. The safety and morbidity of the two groups were compared based on mean operative time, blood loss, intraoperative complications, postoperative complication, etc., and the results were analyzed. Statistical analysis was performed using IBM SPSS statistics version 20. Clinical and pathologic factors were compared between two groups with Fisher's exact test and Student's t-test for data analysis. The survival data were analyzed using Kaplan–Meier survival curves. P < 0.05 was considered statistically significant.Results:Thirty-two patients underwent laparoscopic staging, 45 underwent laparotomy, and 13 cases lap converted to open surgery. The mean operative time for the laparoscopic procedure was lower than the open procedure (P = 0.001). The mean hospital stay of patients who underwent laparoscopic staging was around 7.1 days significantly less compared to the laparotomy group. Intraoperative blood loss of patients undergoing laparoscopic surgery was significantly less than that of the laparotomy group (P = 0.015). There was no statistically significant difference in nodal retrieval between laparotomy and laparoscopy group (P = 0.172). The mean duration of hospitalization was statistically significantly greater in the laparotomy group than the laparoscopic group (13 and 7 days, P < 0.001). Based on the Kaplan–Meier survival curve, there was no difference in survival rates between the groups. Median follow-up duration was 32 months.Conclusion:Laparoscopic surgical staging is oncologically safe for the management of endometrial cancer with acceptable morbidity compared to the open approach with far less blood loss and shorter postoperative stay.

Outcomes of robotic surgery for endometrial cancer in elderly women

IntroductionFew data have been reported on robot-assisted surgery in elderly. The objectives were to compare feasibility, complication data, and survival of patients under and upper the age of 70 who are managed for endometrial cancer by robot-assisted laparoscopy. Materials and methodsThis is a retrospective comparative single-center study including patients treated between January 2007 and December 2016. Patients were divided into 2 groups: less than 70 years and greater than or equal to 70 years. The primary endpoint was the rate of complications. The secondary endpoints were conversion rate and follow-up. Results148 patients were included: 86 under 70 (group A) and 62 aged 70 and over (group B). More adhesiolysis was performed in group B (p < .01); the pelvic and para-aortic lymph node dissection rates were not different between both groups (p = .2 and p = .9). The operating times were significantly longer in group B (220.1 vs. 234.4 min, p = .02). The conversion rate was similar between the 2 groups (p = .7). The tumors were endometrioid adenocarcinomas for 77.9 and 66.7% respectively (p = .2), with grade 3 tumors more represented in older patients (24.4% vs. 48.4%, p < .01). There were more tumors at high risk of recurrence after 70 years (33.7 vs. 45.2%, p = .04). No significant difference was found for postoperative complications. There was no difference in overall survival (p = .7) or progression-free survival (p = .2). Undertreated women rate was similar in both groups (p = .1). ConclusionRobotic surgery appears feasible and reproducible and could bring a benefit and allow optimal surgery without increasing the morbidity in the management of endometrial cancers whatever the age is.

PRMT6 promotes endometrial cancer via AKT/mTOR signaling and indicates poor prognosis.

Arginine methylation plays essential roles in post-transcriptional modification and signal transduction. Dysregulation of protein arginine methyltransferases (PRMTs) has been reported in human cancers, yet the expression and biological function of PRMT6 in endometrial cancer (EMC) remains unclear. Here, we show that PRMT6 is upregulated in EMC and exhibits oncogenic activities via activation of AKT/mTOR pathway. The expression of PRMT6 in EMC is much higher than that in the adjacent nontumorous tissues. Elevated PRMT6 expression is significantly associated with higher histological tumor grade and unfavorable prognosis in two independent cohorts consisting of a total of 564 patients with EMC. In vitro data demonstrate that PRMT6 expression was identified as a downstream target of miR-372-3p. Ectopic expression of miR-372-3p downregulates PRMT6. Overexpression of PRMT6 promotes EMC cell proliferation and migration, whereas knockdown of PRMT6 leads to opposite phenotypes. Mechanistically, PRMT6 induces the phosphorylation of AKT and mTOR in EMC cells. Inhibition of AKT/mTOR signaling by MK2206 or rapamycin attenuates the PRMT6-mediated EMC progression. In clinical samples, high expression of PRMT6 was correlated to low expression of miR-372-3p and high expression of phosphorylated AKT. Collectively, our findings suggest PRMT6 may function as an oncogene to promote tumor progression, and be of prognostic value to predict disease-free survival of patients with EMC. The newly identified miR-372-3p/PRMT6/AKT/mTOR axis represents a new promising target for EMC management.

Incorporation of molecular characteristics into endometrial cancer management.

Histopathological evaluation including subtyping and grading is the current cornerstone for endometrial cancer (EC) classification. This provides clinicians with prognostic information and input for further treatment recommendations. Nonetheless, patients with histologically similar ECs may have very different outcomes, notably in patients with high‐grade endometrial carcinomas. For endometrial cancer, four molecular subgroups have undergone extensive studies in recent years: POLE ultramutated (POLEmut), mismatch repair‐deficient (MMRd), p53 mutant (p53abn) and those EC lacking any of these alterations, referred to as NSMP (non‐specific molecular profile). Several large studies confirm the prognostic relevance of these molecular subgroups. However, this ‘histomolecular’ approach has so far not been implemented in clinical routine. The ongoing PORTEC4a trial is the first clinical setting in which the added value of integrating molecular parameters in adjuvant treatment decisions will be determined. For diagnostics, the incorporation of the molecular parameters in EC classification will add a level of objectivity which will yield biologically more homogeneous subclasses. Here we illustrate how the management of individual EC patients may be impacted when applying the molecular EC classification. We describe our current approach to the integrated diagnoses of EC with a focus on scenarios with conflicting morphological and molecular findings. We also address several pitfalls accompanying the diagnostic implementation of molecular EC classification and give practical suggestions for diagnostic scenarios.

An Externally Validated Nomogram for Predicting Lymph Node Metastasis of Presumed Stage I and II Endometrial Cancer.

Background: Optimal management for endometrial cancer in patients with clinically negative lymph nodes is still under debate. Several prediction models for lymphatic dissemination of early-stage endometrial cancer have been developed. However, external validation is rare, and decision curve analysis has hardly been applied for these models.Objective: To develop and validate a nomogram to predict lymph node metastasis of presumed stage I and II endometrial cancer.Study Design: The prediction nomogram was developed by using multivariable logistic regression with data for 700 EC patients who underwent initial surgery from 2006 to 2017 at Peking University People's Hospital (training dataset), Beijing. External validation was performed in 727 eligible patients from Fudan University Shanghai Cancer Center (validation dataset), Shanghai.Results: For the 700 women in the training dataset, the lymph node metastasis rate was 8.0% (56/700). Lymphovascular space invasion, histological grade, cervical stromal invasion, and myometrial invasion were independent prognostic factors in the training dataset. We generated a nomogram based on these pathological factors. To determine the clinical usefulness of our nomogram, we compared it with the Mayo criteria. For our nomogram, the area under the receiver operating characteristic curve (AUC) was 0.85 as compared with 0.63 for the Mayo criteria. In the validation dataset, the AUC was 0.78 as compared with 0.57 for the Mayo criteria. The nomogram was well-calibrated in both the training and validation datasets. At a 10% probability threshold, our nomogram decreased almost 29 unnecessary lymphadenectomies per 100 patients than the Mayo criteria without missing more metastatic disease.Conclusion: We developed a nomogram to predict lymph node metastasis in patients with early-stage endometrial cancer in China. This prediction model may help clinicians in decision-making for patients with early-stage endometrial cancer, especially for the patient with incomplete surgery, reducing overtreatment, and medical costs.

Downregulation of Proline Hydroxylase 2 and Upregulation of Hypoxia-Inducible Factor 1α are Associated with Endometrial Cancer Aggressiveness.

IntroductionProline hydroxylase 2 (PHD2) is involved in tumorigenesis. This study aimed to examine PHD2 and hypoxia-inducible factor 1α (HIF-1α) expression in different endometrial tissues and explore the correlations between PHD2 and HIF-1α expression with clinicopathological characteristics of endometrial cancer.MethodsWe collected 50 tissue sections of endometrial adenocarcinoma, 30 of atypical endometrial hyperplasia, and 30 of control normal endometrium. The expression of PHD2 was detected by PCR, Western blot, and immunohistochemical analysis.ResultsPHD2 mRNA and protein levels reduced in endometrial cancer tissues compared to normal endometrium (p<0.05). In contrast, HIF-1α expression levels increased in endometrial cancer tissues compared to normal endometrium (p<0.05). In addition, PHD2 and HIF-1α levels were correlated with lymphovascular stromal invasion (LVSI), postoperative FIGO stage, and lymph node metastasis of endometrial cancer (p<0.05).ConclusionOur findings suggest that reduced expression of PHD2 and increased expression of HIF-1α are associated with endometrial cancer aggressiveness. PHD2 might be a novel biomarker and a potential target for endometrial cancer management.

Clinical and biological significance of EZH2 expression in endometrial cancer

ABSTRACTThe objective of this study was to examine the clinical significance of EZH2 expression and the therapeutic efficacy of its silencing in endometrial cancer. EZH2 expression in clinical samples was evaluated using a tissue microarray and correlated with clinical outcomes. The biological roles of EZH2 were assayed in vitro and in vivo. Gene expression was examined to reveal the molecular mechanism underlying the roles of EZH2 in endometrial cancer. We found that EZH2 overexpression was significantly correlated with disease-free and overall survival of patients with endometrial cancer. EZH2 silencing resulted in decreased cell viability and invasiveness, and increased apoptosis. In addition, EZH2 silencing enhanced the cytotoxicity of taxanes and cisplatin in Hec-1A and Ishikawa endometrial cancer cells. EZH2 silencing using small-interfering RNA (siRNA) incorporated into chitosan nanoparticles (siRNA/CN) induced a significant anti-tumor effect compared with that observed in controls (66.6% reduction in Hec-1A cells and 63.2% reduction in Ishikawa cells, p < .05 for both). Moreover, EZH2 siRNA/CN in combination with taxanes produced more robust anti-tumor effects versus those induced by monotherapies (77.0% for Hec-1A cells and 57.7% for Ishikawa cells, p < .05 for both). These results were associated with decreased angiogenesis and cell proliferation, and enhanced apoptosis. Genomic analyses revealed that EZH2 silencing decreased the expression levels of many genes associated with tumor growth, including PRDX6. Collectively, these results support EZH2 as an attractive target for the therapeutic management of endometrial cancer.

Transvaginal Laparoscopy for Management of Low-Grade Endometrial Cancer

Study Objective to report on our experience with transvaginal laparoscopic management of low-grade endometrial cancer. Design a study of transvaginal natural orifice endoscopy to manage patients with grade 1 or grade 2 endometrial cancer. This is descriptive of the surgical findings and consequences. Setting a single institution academic center Patients or Participants 32 women with low-grade endometrial cancer were consented for hysterectomy, bilateral salpingo-oophorectomy (BSO) by a transvaginal approach utilizing laparoscopy. Interventions Anterior and Posterior cul-de-sacs were opened through the vagina. A gel point device was placed into these spaces, the patients reclined in slight Trendelenburg position, and the abdomen insufflated. A vessel sealing device was used under laparoscopic visualization to cauterize and cut the paracervical tissue, uterosacral ligaments, uterine vasculature, broad ligament and utero-ovarian pedicle. The uterus was removed and submitted to pathology for depth of invasion. The tubes and ovaries were then removed laparoscopically and the entire abdominal cavity was inspected. Patients with deep invasion underwent trans-abdominal laparoscopic lymphadenectomy. Measurements and Main Results a total of 32 women underwent the procedure. The mean age was 60(26 – 90). The mean BMI was 34(22 – 58). 19 had prior pelvic surgery including eight with one or more prior cesarean deliveries. The mean uterine weight was 119 g (27 – 436). 12 patients were discharged home that day and 20 stayed overnight. One patient had a thermal injury to the small bowel requiring over sewing. Two patients had bladder injury during entry to the Anterior cul-de-sac, both of whom had had two prior cesarean deliveries. One patient required lymphadenectomy. Patients did not require narcotic analgesia. Conclusion transvaginal laparoscopic hysterectomy, BSO is feasible and permits rapid recovery with minimal postoperative pain and is cosmetically appealing.

Geographic variation in the use of lymphadenectomy and external-beam radiotherapy for endometrial cancer: a cross-sectional analysis of population-based data.

To quantify geographic variation in the use of lymphadenectomy and/or external-beam radiotherapy (EBRT) for endometrial cancer in England. Cross-sectional analysis of population-based data. English cancer registry data, linked to chemotherapy, radiotherapy and hospital episodes statistics data. Twenty-two thousand four hundred and eighty-three women with endometrial cancer presenting without clinical or radiological evidence of distant metastatic spread, diagnosed in England from 2013 to 2016. Proportions of patients receiving lymphadenectomy and/or EBRT were compared across 19 Cancer Alliances, to identify variations in clinical practice. Two separate logistic regression models assessed the impact on variation of adjustment for tumour and patient characteristics. Receipt of lymphadenectomy, receipt of EBRT. There was substantial variation by Cancer Alliance in the adjusted proportion of women with endometrial cancer receiving lymphadenectomy (range 5% [95% CI 4-6%] to 48% [95% CI 45-52%]) and EBRT (range 10% [95% CI 7-12%] to 31% [95% CI 28-33%]), after adjusting for variation in pathological grade, age, comorbidities, deprivation, ethnic group and (EBRT only) FIGO stage. Different approaches to clinical practice were identified; (i) one Cancer Alliance had significantly higher than average lymphadenectomy and significantly lower than average EBRT use, (ii) three had high use of both lymphadenectomy and EBRT, (iii) one had low lymphadenectomy use and high EBRT use, and (iv) three had low use of both lymphadenectomy and EBRT. Lymphadenectomy is probably used to triage for EBRT when lymphadenectomy use is high and EBRT use is low. This is probably a result of variation in local endometrial cancer management guidelines, suggesting that UK recommendations should be clarified. There is geographic variation in England in the use of lymphadenectomy and radiotherapy to treat endometrial cancer.

Management of endometrial cancer in patients aged 80 years and older: Identifying patients who may benefit from a curative treatment

ObjectiveThe goal of this study was to evaluate the demographic characteristics, pathology, treatment, prognostic factors and survival rates in elderly patients with endometrial cancer, and to compare their results with those of younger ones, in order to define the specific characteristics of this malignancy in this population.Study design: Retrospective analysis of all endometrial cancer patients managed at the University Hospital of the Canary Islands (Spain) between 1990 and 2016. Survival curves were calculated by using the Kaplan-Meier method and compared with the log-rank test. Logistic regression analysis was used to assess the independent effect of different variables on cancer-specific survival. Statistical significance was considered for p < 0.05. ResultsThe study included 1799 endometrial cancer patients; 170 of them (9.4%) were 80 years old or older. Elderly patients received less surgery (68.2% vs. 92.4%), lymphadenectomy (10.3% vs. 26.2%) and adjuvant treatment (37.1% vs. 51.2%) than younger ones, and presented higher probability of receiving palliative treatment (27.6% vs. 4%). Endometrioid tumors were more frequently diagnosed in younger patients (78.8% vs. 62.9%), while type 2-endometrial cancer was more frequently diagnosed in elderly ones (37.1% vs. 21.2%).Cancer-specific survival in older patients was significantly poorer than in younger ones, with a mean of 61.4 months (95%CI 51.7–71.1) versus 226 months (95%CI 218.9–233.1), respectively. In a multivariate analysis: age, FIGO stage, histology, tumor differentiation and adjuvant treatment were independently associated with survival. ConclusionAlthough endometrial cancer is more aggressive in older patients, they are less likely to receive optimal treatment, which negatively affects their survival. Specific guidelines for the management of this population, including a comprehensive geriatric assessment, should be developed to improve their prognosis.

Endometrial cancer and obesity

Key content Of the 20 most common tumour types, endometrial cancer has the strongest association with obesity. Endometrial cancer should be considered in young, obese women with irregular or heavy menstrual bleeding. To reduce the risk of postoperative complications, surgery for endometrial cancer should be performed using minimal access techniques whenever possible. For women who are unfit for, or who decline, surgery, alternative treatments include progestins or radiotherapy, but these have lower efficacy and are associated with a higher risk of disease relapse. Obesity is associated with reduced overall survival following endometrial cancer because of increased cardiovascular mortality; it may also affect disease‐specific survival. Learning objectives To further understanding of the mechanisms through which obesity drives endometrial carcinogenesis. To improve understanding of the potential difficulties associated with the management of endometrial cancer in obese women. To increase knowledge of alternative treatment options for women who are unfit for, or who decline, standard endometrial cancer management. Ethical issues The number of young, premenopausal women with endometrial cancer is increasing – how should these women be managed? Should super‐obese women with endometrial cancer only be treated in cancer centres? After treating a woman's endometrial cancer, how should she be counselled her about her weight and cardiovascular disease risk?

Clinical Outcomes of Endometrial Cancer Patients By Microsatellite Instability Status

Endometrial cancer is the most common gynecological malignancy in the United States. Up to one third of all endometrial tumor types exhibit microsatellite instability (MSI). The influence of this genetic aberration on treatment outcomes remains unclear. We compared the clinical outcomes of patients whose tumors demonstrated MSI to those whose tumors were microsatellite stable. We conducted a retrospective chart review of 35 sequential patients with non-metastatic endometrial cancer who had been tested for MSI status who underwent curative surgery and radiation and/or chemotherapy January 2013 and December 2016 at a single institution. Information regarding demographics, clinical & pathologic tumor characteristics, treatment modalities, recurrence, and survival were recorded. Age, stage, histology, grade, and lymphovascular invasion (LVSI) were compared with Fisher’s Exact test. Survival and recurrence estimates were calculated using to Kaplan-Meier method and compared by the log–rank test. 19 tumors were reported microsatellite stable and 16 were microsatellite unstable. Median follow up for the whole cohort was 34.1 months. There were no significant differences between groups in age, histology, stage, grade, LVSI, or myometrial invasion (Table 1). Between patients with microsatellite stable and microsatellite unstable tumors, there was no difference in rates of local or distance recurrence between groups (10.5% vs. 25.0%, p=0.76 and 21.1% vs 6.3%, p=0.58, respectively). Survival was also not found to be significantly different between groups (median survival microsatellite stable 33.7 months vs 34.2 months microsatellite unstable, p=0.37). In patients undergoing definitive management of non-metastatic endometrial cancer, tumor microsatellite instability was not associated with significant differences in adverse pathologic features at presentation nor differences in recurrence rates or survival. Additional studies are warranted to confirm any prognostic and/or predictive value of tumor MSI status in the treatment of endometrial cancer.Abstract 2812; Table 1Clinical characteristics of endometrial cancer patients by MSI statusCharacteristicMSI stable n = 19MSI unstable n = 16p-valueCharacteristicMSI stable n = 19MSI unstable n = 16p-valueStage1A, 1B1490.479Grade1230.2382, 2A2328103, 3B, 3C243934B10Lymphovascular invasionPositive1090.830HistologyEndometrioid13150.101Negative86Serous30Myometrial invasionConfined200.625Mixed20<50%65Clear cell10>50%1111Other01Age in years, median (IQR)64 (57-71)68 (56-72.5)0.501 Open table in a new tab

Utilizing the Radiosensitivity Index (RSI) to Predict Pelvic Failure in Endometrial Cancer Treated with Adjuvant Radiotherapy

Various adjuvant approaches are utilized in the management of endometrial cancer based on surgical pathology and institutional preference. The radiosensitivity index (RSI) is a previously validated multi-gene expression index that estimates tumor radiosensitivity. In this study, we evaluate RSI as a genomic predictor for pelvic failure (PF) in patients treated with adjuvant radiotherapy. A total of 204 consecutively treated patients with endometrial cancer were identified from our IRB-approved institutional tissue biorepository. All patients underwent hysterectomy with bilateral salpingo-oophorectomy with the majority undergoing lymph node dissection (n=181; 88%) between 01/99 and 04/11 and followed until 01/19. Gene expression was from Affymetrix Hu-RSTA-2a520709 (Affymetrix; Santa Clara, CA). The RSI 10-gene signature was calculated for each sample using the previously published algorithm. Radiophenotype was determined by dichotomization of RSI at the previously identified cutpoint of 0.375; ≥0.375 = radioresistant (RR) and <0.375 = radiosensitive (RS). Time to event analysis was performed with Kaplan-Meier estimates and the log-rank test. Associations between radiophenotype and outcomes were explored with univariable (UVA) and multivariable (MVA) Cox regression. The threshold for statistical significance in all tests was set at p<0.05. Median follow-up was 38.5 months (range: 0.2-216). The median RSI was 0.42 (range: 0.11-0.70). There were no significant differences in RS and RR patients in age (p=0.99), serosa and/or adnexa involvement (p=0.37), vaginal and/or parametrial involvement (p=0.48), cervical stromal invasion (p=0.59), receipt of adjuvant chemotherapy (p=0.12), and node involvement (p=0.78). A total of 83 (41%) patients were treated with adjuvant radiotherapy with vaginal brachytherapy (n=19; 23%), pelvic radiotherapy (n=26; 31%), or both (n=38; 46%). In patients treated with radiation, RR patients were more likely to undergo PF (3 year pelvic control 84% vs 100%; p=0.02) with worse PF free survival (PFFS) (3 year PFFS 65% vs. 89%; p=0.04). However, since RSI is a radiation specific signature it did not predict PF (p=0.86) or PFFS (p=0.57) in patients not treated with radiation. Factors found to predict PF on UVA included grade 3/1-2 (HR 3.8; 95% CI 1.2-14.8, p=0.03), serosa and/or adnexa involvement (5.9; 95% CI 1.6-20.2, p=0.008), lymph node involvement (4.9; 95% CI 1.5-18.8, 0.009), and RR/RS (7.7; 95% CI 1.5-140.9, 0.01). On MVA, factors that continued to predict for PF included RR/RS (10.7; 95% CI 1.9-202.4, p=0.004), lymph node involvement (4.1; 95% CI 1.2-16.3, p=0.03), and serosa and/or adnexa involvement (4.3; 95% CI 1.2-16.4, p=0.03). RSI was found to be a significant predictor of PF in patients treated with adjuvant radiotherapy on MVA. We propose RSI may be a method to predict which patients are most likely to fail in the pelvis and candidates for treatment escalation in the adjuvant setting.

Surgery in Endometrial Cancer: An Audit of Quality Across Centers in India

Surgical management is the cornerstone in the treatment of endometrial cancer. However, there are many controversies involved in the management starting from what constitutes adequate staging to the type of adjuvant treatment. In India, surgeons from several specialties operate on patients with endometrial cancer and there is a lack of guideline-based practice which necessitates an audit on the quality of care offered to women with endometrial cancer. The study was a questionnaire-based study conducted at various conference venues. The study participants included general surgeons, gynecologists, surgical oncologists and gynecologic oncologists who operate on endometrial cancer. There is an extensive variation in the management of endometrial cancer among practitioners and lack of consensus regarding lymphadenectomy and its extent during surgery. Also, the use of intraoperative frozen section and comprehensive staging is more commonly seen among oncosurgeons when compared to other specialties.

Management of high-risk endometrial cancer: are we there yet?

Management of high-risk endometrial cancer: are we there yet?