Treatment Of Endometrial Cancer Research Articles

Risk Stratified Follow-Up for Endometrial Cancer: The Clinicians' Perspective.

Risk-stratified follow-up for endometrial cancer (EC) is being introduced in many cancer centres; however, there appears to be diversity in the structure and availability of schemes across the UK. This study aimed to investigate clinicians' and clinical specialist nurses' (CNS) experiences of follow-up schemes for EC, including patient-initiated follow-up (PIFU), telephone follow-up (TFU) and clinician-led hospital follow-up (HFU). A mixed-methods study was conducted, consisting of an online questionnaire to CNSs, an audience survey of participants attending a national "Personalising Endometrial Cancer Follow-up" educational meeting, and qualitative semi-structured telephone interviews with clinicians involved in the follow-up of EC. Thematic analysis identified three main themes to describe clinicians' views: appropriate patient selection; changing from HFU to PIFU schemes; and the future of EC follow-up schemes. Many participants reported that the COVID-19 pandemic impacted EC follow-up by accelerating the transition to PIFU/TFU. Overall, there was increasing support for non-HFU schemes for patients who have completed primary treatment of EC; however, barriers were identified for non-English-speaking patients and those who had communication challenges. Given the good long-term outcome associated with EC, greater focus is needed to develop resources to support patients post-treatment and individualise follow-up according to patients' personal needs and preferences.

Fertility-Sparing Management of Early Stage Endometrial Cancer: A Narrative Review of the Literature

Objectives: The incidence of endometrial cancer (EC) is rising largely due to the increasing levels of obesity along with an ageing population. This has led to an increase in the incidence of premenopausal women with EC. 5% of cases are in patients less than 40 years old, 70% of which are nulliparous at diagnosis. Therefore, fertility considerations must be taken into account when managing these patients. The objectives of this review are to present the fertility-sparing management options available. Mechanism: A detailed computerized literature search of PubMed and MEDLINE up to 1st June 2022 was carried out in order to survey the evidence for fertility-sparing treatment. Studies including patients with endometrial hyperplasia and early-stage EC undergoing fertility-sparing management were included. Findings in Brief: Progestin acts by downregulating oestrogen receptors, thereby suppressing endometrial growth. Oral progestins and the levonorgestrel-releasing intrauterine system (IUS) have therefore been used as non-surgical hormonal treatment for EC. Megestrol acetate (MA) has been shown to produce the highest remission rates compared to other progestins in a systematic review and meta-analysis, but medroxyprogesterone acetate exhibited lower recurrence rates. The IUS for atypical hyperplasia (AH) and EC showed that the majority of patients responded by 3 months’ use. A minimum duration of hormonal treatment for AH and EC of 6 months has been advocated, based on randomised studies showing greater efficacy when compared to 3 months treatment. A meta-analysis and systematic review assessing the efficacy of both oral and intra-uterine progestins showed a higher pooled complete response (CR) than with IUS alone. Metformin, gonadotrophin-releasing hormone agonists and weight loss have also been added to progestin regimes with variable results on EC regression. Hysteroscopic resection allows for targeted excision of early-stage EC, but with the risk of perforation and so this has not been recommended by the British Gynaecological Cancer Society or the European Society of Gynaecological Oncology. Assisted reproduction treatment (ART) may be the quickest way to achieve pregnancy once CR is achieved. Pregnancy rates have varied from 32–100%, with live birth rates varying from 17.9–43.8%. Conclusions: EC incidence is on the increase in the premenopausal population along with obesity rates and the average first age of parenthood. Fertility-sparing management of EC should be considered for women where fertility is desired.

Mismatch repair deficiency, next-generation sequencing-based microsatellite instability, and tumor mutational burden as predictive biomarkers for immune checkpoint inhibitor effectiveness in frontline treatment of advanced stage endometrial cancer

ObjectiveMolecular profiling is developing to inform treatment in endometrial cancer. Using real world evidence, we sought to evaluate frontline immune checkpoint inhibitor vs chemotherapy effectiveness in advanced endometrial cancer, stratified...

Identification of stemness subtypes and features to improve endometrial cancer treatment using machine learning

Endometrial cancer is one of the most common malignant tumours in women, and cancer stem cells are known to play an important role in its growth, invasion, metastasis, and drug resistance. Immunotherapy for endometrial cancer is still under research. In this study, a total of 547 endometrial cancer cases were randomly divided into training set (351 cases) set and test set (196 cases). The stemness index of patients was calculated using the One-Class Logistic Regression (OCLR) machine learning algorithm to explore the clinicopathological differences between index levels. Stemness subtypes were determined according to the characteristics of cancer stemness and their clinicopathological characteristics, immune features, and therapeutic effects were described. Our study suggests that endometrial cancer is classified into two stemness subtypes. Stemness subtypes, which are associated with its clinical features, may be independent prognostic factors for endometrial cancer. The stemness subtypes differed significantly in immune activity, immune cell infiltration, and the immune microenvironment, including sensitivity to chemotherapeutic drugs and potential therapeutic compounds. Algorithms were utilised to construct a stemness subtype prediction model and predictor. These findings will provide guidance for the clinical diagnosis, treatment, and prognosis of endometrial cancer.

Surgical Outcomes Following Robotic Single-Site Versus Multiport Hysterectomy for Treatment of Endometrial Cancer: A Systematic Review and Meta-Analysis.

Robotic single-site hysterectomy (RSSH) has emerged as a novel surgical approach for the treatment of endometrial cancer and atypical endometrial hyperplasia (AEH). Current research regarding the benefits of RSSH compared to robotic multiport hysterectomy (RMPH) for these indications has been inconclusive. Our team sought to compare surgical outcomes between these two approaches ofrobotic hysterectomy via systematic review and meta-analysis to ensure optimal surgical practices. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Checklist guided our review. MEDLINE, Clinicaltrials.gov, and Cochrane Library were searched, yielding 59 results. Articles were filtered by title and abstract and then reviewed in full for inclusion and exclusion criteria. Inclusion criteria required that (1) studies compared outcomes for RSSH and RMPH, (2) hysterectomy was indicated for endometrial cancer or hyperplasia with atypia, and (3) studies were available in English. Excluded studies (1) compared single-site and multiport laparoscopic approaches, (2) compared robotic approaches to laparoscopic or abdominal (open) techniques, and (3) employed hysterectomy for benign conditions. Publication bias was assessed using the Egger Regression Correlation analysis. Four studies complied with the selection criteria, comprising 138 patients in the RSSH group and 259 in the RMPH group. Similar outcomes were noted across all measures, including conversion rate (relative risk [RR] = 1.84 and confidence interval [CI] = 0.99-3.43), blood loss (Cohen's d = 1.05 and Z = 18.62), operating time (Cohen's d=0.29 and Z=4.38), and length of hospital stay (Cohen's d= 1.06 and Z= 3.86). Publication bias was deemed minimal as indicated by Egger regression values of less than 0.05. These findings suggest that either a surgical approach or AEH with the proper standard of care can provide patients with endometrial cancer.

Dostarlimab for Endometrial Cancer: A Comprehensive Review of Clinical Outcomes

Jemperli (dostarlimab) is an anti-PD-1 mab used to treat endometrial cancer. It is a humanized mab produced using rdna technology in CHO cells. It is approved in the US and EU and was developed by Tesaro, later acquired by GlaxoSmithKline. Clinical trial data on dostarlimab was reviewed using online sources such as PubMed, Cochrane, and Medscape. The review included English language clinical trials, randomized trials, original articles, newsletters, and letters to the editor. Results from the GARNET clinical trial an open-label, multicohort study, which showed reduced progression and recurrence of cancer in treated individuals, led to the approval of dostarlimab. In some cases, the cancer was undetectable during imaging scans during treatment with the drug. Keywords: Jemperli, Dostarlimab, Anti-PD-1, GARNET clinical trial, Treatment, Endometrial cancer treatment, Cancer therapy.

JGOG2046: a feasibility study of neoadjuvant chemotherapy followed by debulking surgery for clinically diagnosed FIGO stage IVb endometrial cancer.

We evaluated the feasibility of neoadjuvant chemotherapy, followed by debulking surgery, for clinically diagnosed FIGO stage IVb endometrial cancer (protocol number: JGOG2046). The experimental treatment consisted of 3 cycles of paclitaxel (180mg/m2) plus carboplatin (AUC5) followed by debulking surgery, including total abdominal hysterectomy, bilateral salpingo-oophorectomy, and 3 cycles of adjuvant chemotherapy. Patients were considered as eligible if they were pathologically diagnosed as primary endometrial cancer, and had both endometrial tumor and distant metastasis confirmed by imaging examinations. The primary endpoint was the incidence of patients who completed debulking surgery after the neoadjuvant chemotherapy. While 51 patients were enrolled from 23 hospitals, the final study cohort consisted of 49 patients with a mean age of 59.0years. Although the response ratio of the neoadjuvant chemotherapy was 65.3% (95% CI 50.4-78.3%), 67.3% (95% confidence interval (CI) 52.5-80.1%) underwent debulking surgery after the neoadjuvant chemotherapy and 59.2% (95% CI 45.2-71.8%) completed the protocol treatment including 3 courses of adjuvant chemotherapy. The median disease-free survival time was 9.1months (95% CI 6.5-11.9), while the median overall survival time was 23.2months (95% CI 11.9-27.8). A patient with sigmoid colon cancer and another with cervical cancer were included in this study. Neoadjuvant chemotherapy followed by debulking surgery was a feasible and acceptable treatment for metastatic endometrial cancer. (225 words).

COMPARATIVE ANALYSIS OF THE USE OF MAINTENANCE THERAPY DRUGS IN WOMEN IN THE PROCESS OF RADIOTHERAPY AFTER SURGICAL TREATMENT OF ENDOMETRIAL CANCER

Aim. To carry out a comparative analysis of the cost of a "unit of effect" of emoxipin, ethoxidol and mexidol used to improve the quality of life of women receiving radiation therapy after surgical treatment of endometrial cancer. Materials and methods. The pharmacoeconomic analysis was carried out in accordance with the Guidelines for Calculating Costs in Conducting Clinical and Economic Studies of Medicinal Products and included determining the position of the study and the list of costs, the time period for cost accounting and cost calculation. The results of the use of the studied drugs were evaluated according to the previously published dynamics of integrative indicators of QL according to the generic questionnaire SF-36 and the cancer-specific questionnaire for patients with endometrial cancer FACT-En. In the course of the analysis, a comparison was made of the direct costs (Cost, in rubles) for the purchase of each of the studied drugs with the consequences (Ef) of their course use. The result of the pharmacoeconomical analysis was expressed in the form of a cost-effectiveness coefficient (CER = Cost / Ef) per patient. Results. As a result of the clinical and economic analysis, it was found that in most cases mexidol is characterized by the lowest cost-effectiveness ratio. This concerns the calculation of CER according to the dynamics of the integral indicator (TS) of the questionnaire for the functional assessment of endometrial cancer therapy (FACT-En) and the psychological component of health (MH) according to SF-36. The exception was the result of the calculation of "cost-effectiveness" according to the criterion of increasing PH – the physical component of health according to SF-36. In this situation, mexidol was inferior to ethoxidol in terms of pharmacoeconomic efficiency. In all cases, without exception, the most expensive was the use of emoxipin. Conclusion. According to the pharmacoeconomic criterion "costs - effectiveness", the most expensive is the use of emoxipin, and the least expensive is the use of mexidol. In all cases, the "cost per unit effect" of emoxipin was 3-6 times higher than the corresponding indicators of mexidol and ethoxidol.

Carboplatin-loaded Ultradeformable Vesicles for the Management of Endometrial Cancer: In Vitro and In Vivo Evaluation

Aim: Present research work aimed to explore intravaginal route for the drug delivery for treatment of endometrial cancer (EC). Material & methods: Carboplatin (CBP)-loaded ultradeformable vesicle (CBP-UDV) was prepared and characterized for invitro quality attributes and evaluated for its efficacy in rabbits using ultrasound imaging after intravaginal administration. Results & conclusion: The results showed that the formulation capable of carrying and localizing drug in uterus for prolonged period assisted by first uterine pass effect. Ultrasound imaging of the EC-induced rabbit model before and after treatment with CBP-UDV showed considerable regression in the EC tumor mass. The findings serve as the basis of successful utilization of the intravaginal route for management of EC by designing the formulation which can improve patient compliance.

SLERT, as a novel biomarker, orchestrates endometrial cancer metastasis via regulation of BDNF/TRKB signaling

BackgroundRecent evidence suggests that the box H/ACA small nucleolar RNA (snoRNA)-ended long noncoding RNA (lncRNA), SLERT, plays a critical role in gene regulation. However, its role in cancer remains undetermined. Herein, we explored its implication in human endometrial cancer (EC).MethodsEC plasma and tissue samples were collected for the detection of SLERT expression using qRT-PCR method. The functional investigation was tested by CCK-8 and transwell assays. Luciferase reporter, RNA pull-down, and immunoprecipitation (RIP) assays were used to determine the regulatory network involved in SLERT. The in vivo effect of SLERT was tested by caudal vein lung metastasis model.ResultsStable knockdown of SLERT significantly inhibited EC cell (KLE and AN3CA) migration and invasion, while it did not affect cell viability. SLERT induced epithelial-mesenchymal transition (EMT) via elevating N-cadherin and Vimentin and downregulating E-cadherin. Further investigation showed that SLERT directly binds to METTL3, increasing the m6A levels of BDNF mRNA; then, the m6A sites were read by IGF2BP1, enhancing BDNF mRNA stability, followed by the activation of BDNF/TRKB signaling, an inducer of EMT. The animal model showed that overexpression of SLERT increased EC cell lung metastasis, and this effect was effectively blocked by BDNF silencing or treatment with TRKB inhibitor k252a. Clinically, EC patients have high levels of SLERT both in tissue or plasma, which might be used as a biomarker of diagnosis and prognosis.ConclusionOur findings, for the first time, uncover the metastasis-promoting effect of SLERT in EC via in vitro and in vivo evidence, providing a potential therapeutic target for metastatic EC treatment.

Fertility Preservation in Endometrial Cancer-Treatment and Molecular Aspects.

Endometrial cancer is one of the most common gynecological malignancies worldwide; incidences are rising, with 417,367 new cases registered in 2020. Of these, the proportion of women that are of reproductive age is around 4-14% and the number is increasing. Thus, in addition to oncological therapy and safety, the preservation of fertility plays a central role in therapeutic strategies. Molecular genetic patient data provide a robust supplementary benefit that improves primary risk assessment and can help design personalized treatment options to curtail over- and undertreatment and contribute to fertility preserving strategies. The aim of our review is to provide an overview of the latest significant recommendations in the diagnosis and therapy of endometrial cancer during reproductive age. In this paper the most recent groundbreaking molecular discoveries in endometrial cancer are highlighted and discussed as an opportunity to enhance the prognostic and therapy options in this special patient collective.

Obstetric outcomes after medroxyprogesterone acetate treatment for early stage endometrial cancer or atypical endometrial hyperplasia: a single hospital-based study.

To investigate perinatal outcomes in pregnancy after high-dose medroxyprogesterone acetate (MPA) therapy for early stage endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) and to determine whether pregnancy after MPA therapy is at a higher risk of placenta accreta. Data of 51 pregnancies in 46 women who received MPA therapy for EC or AEH and delivered after 22weeks of gestation at Keio University Hospital were reviewed. A retrospective matched case-control study was performed to determine the risk of placenta accreta in pregnancy after MPA therapy compared with singleton pregnancies without any history of maternal malignancy treatments. The incidence of placenta accreta was higher in the MPA group than in the control group (15.7 vs. 0%, p = 0.0058). However, no differences in other perinatal outcomes were observed between groups. While gestational weeks at delivery in the MPA group were later than those in the control group (p = 0.0058), no difference in the incidence of preterm delivery was recorded between groups. In the MPA therapy group, the number of patients who underwent ≥ 6 dilation and curettage (D&C) was higher in the placenta accreta group than in the non-placenta accreta group (50.0 vs. 14.0%, p = 0.018). Patients with ≥ 6 D&Cs demonstrated a 6.0-fold increased risk of placenta accreta (p = 0.043, 95% CI 1.05-34.1) than those receiving ≤ 3 D&Cs. Pregnancy after MPA therapy is associated with a high risk of placenta accreta. In cases in which the frequency of D&C is high, placenta accreta should be considered.

Invasiveness of endometrial cancer cell lines is potentiated by estradiol and blocked by a traditional medicine Guizhi Fuling at clinically relevant doses.

The Traditional Chinese medicine, Guizhi Fuling (here called Fuling), has been confirmed in meta-analysis studies to reduce recurrence of endometriosis and improve pregnancy outcomes; however, the possible use of Fuling as a fertility-preserving treatment in endometrial cancer has not previously been tested. Results here are the first to demonstrate dose-dependent inhibition of cell motility by Fuling in two endometrial cancer cell lines, classified as Grade I which is responsive to progesterone treatment, and Grade III (MFE-280) which is resistant. The major outcome of this study was the novel demonstration that Fuling (30-80 µg/ml) significantly inhibits invasiveness in both high and low grades of EC cells, achieving 70-80% block of trans-barrier migration without cytotoxicity. This effective dose range is estimated to be comparable to that used in human clinical trials and traditional practice. Results here further show that clinically relevant doses of Fuling override the motility-promoting effects of estradiol in endometrial cancer cell lines. Medroxyprogesterone acetate has to date been the standard therapy to treat metastatic or inoperable endometrial cancers; however, success rates are low with high rates of recurrence, due in part to acquired resistance to medroxyprogesterone acetate therapy. The discovery here that Fuling appears to control the spread of treatment-resistant advanced cancers is an exciting prospect.

Gene signature and prognostic value of ubiquitination-related genes in endometrial cancer

Protein ubiquitination is closely related to tumor occurrence and development. The specific role of ubiquitination in endometrial cancer remains largely unclear. Therefore, we constructed a novel endometrial cancer prognostic model based on ubiquitination-related genes. We extracted the expression matrices of ubiquitination-related genes from the Cancer Genome Atlas database, upon which we performed univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses to obtain 22 ubiquitination-related genes for the construction of the prognostic model. Survival, regression, clinical correlation, and principal component analyses were performed to assess the performance of the model. Drug sensitivity analysis was performed based on these ubiquitination-related genes. Finally, a prognostic nomogram was constructed based on the prognostic model to quantify patient outcomes. Survival, regression, clinical correlation, and principal component analyses revealed that the performance of the prognostic model was satisfactory. Drug sensitivity analysis provided a potential direction for the treatment of endometrial cancer. The prognostic nomogram could be used to effectively estimate the survival rate of patients with endometrial cancer. In summary, we constructed a new endometrial cancer prognostic model and identified 5 differentially expressed, prognosis-associated, ubiquitination-related genes. These 5 genes are potential diagnostic and treatment targets for endometrial cancer.

Molecular Targets and Mechanisms of Callerya nitida Benth. var. hirsutissima Z. Wei in the Treatment of Endometrial Cancer

Molecular Targets and Mechanisms of Callerya nitida Benth. var. hirsutissima Z. Wei in the Treatment of Endometrial Cancer

Lymphocyte activation gene (LAG)-3 is a potential immunotherapeutic target for microsatellite stable, programmed death-ligand 1 (PD-L1)-positive endometrioid endometrial cancer.

Immune checkpoint inhibitors have been widely used in the treatment of endometrial cancer (EC) with microsatellite instability-hypermutated (MSI-H). However, there is an unmet need for microsatellite stable (MSS) EC because of their modest activity. This study aimed to identify potential immune-related biomarkers in MSS EC. One hundred and twenty-three patients with EC who underwent hysterectomy were enrolled. MSI status was determined using MSI analysis and/or immunohistochemical staining for mismatch repair proteins. Immunohistochemical analysis of programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), PD-L2, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), cluster of differentiation 3 (CD3), CD8, lymphocyte activation gene-3 (LAG-3), indoleamine 2,3-dioxygenase 1 (IDO1), phosphatase and tensin homolog (PTEN), p53, AT-rich interactive domain-containing protein 1A (ARID1A), and β-catenin was performed using tissue microarray blocks. Among 123 patients, 95 (77.2%) were classified as having MSS. Within EC with MSS, PD-L1 positivity was significantly associated with positive PD-1 (p<0.001), CTLA-4 (p<0.001), CD3 (p=0.002), CD8 (p<0.001), and LAG-3 (p<0.001). In the univariate analysis, positive PD-1 (odds ratio [OR]=9.281; 95% confidence interval [CI]=2.560-33.653; p<0.001), CTLA-4 (OR=5.33; 95% CI=1.418-19.307; p=0.005), CD3 (OR=5.571; 95% CI=1.746-17.775; p=0.004), CD8 (OR=6.909; 95% CI=2.647-18.037; p<0.001), and LAG-3 (OR=9.75; 95% CI=1.947-48.828; p=0.005) were significantly associated with PD-L1 positivity in MSS EC. In the multivariate analysis, LAG-3 demonstrated a significant association with positive PD-L1 expression in MSS EC (OR=5.061; 95% CI=1.534-16.693; p=0.023). In patients with MSS EC harboring PD-L1, LAG-3 may be a potential immunotherapeutic target. Clinical trials investigating the role of anti-LAG-3 antibodies, alone or in combination with other immunotherapies, are warranted.

The Glutaminase Inhibitor Compound 968 Exhibits Potent In vitro and In vivo Anti-tumor Effects in Endometrial Cancer.

Glutamine is one of the primary nutrients utilized by cancer cells for energy production and biosynthesis. Hence, interfering with glutamine metabolism may impose anti-tumor effects. In this study, we assessed the anti-tumorigenic effects of glutaminase-1 enzyme (GLS1) inhibition in endometrial cancer in vitro and in vivo. The human endometrial cancer cell lines Ishikawa and HEC-1B were used. The effects of compound 968 on cell proliferation, cell cycle, apoptosis, cellular stress, and AKT/mTOR pathway inhibition were assessed. The synergistic effects of compound 968 and paclitaxel were also analyzed. The in vivo effect of compound 968 was evaluated using tumor xenografts. We found that the GLS1-targeting compound 968 was able to reduce cancer cell proliferation in a dose- and time-dependent manner. Compound 968 combined with a low concentration of paclitaxel showed stronger inhibitory effects. Further analyses indicated that compound 968 induced cell cycle arrest at the G1 phase, as well as increased the production of cellular reactive oxygen species (ROS) and promoted cellular stress and cancer cell apoptosis. Additionally, the treatment of endometrial cancer with compound 968 downregulated the expression of GLS1 and cyclin D1 and upregulated the expression of P21 and E-cadherin. Moreover, the treatment of endometrial cancer cells with compound 968 significantly reduced the levels of phospho-S6 ribosomal protein and phospho-AKT (Ser473), indicative of AKT/mTOR/S6 signaling pathway inhibition. In xenograft mouse models of endometrial cancer, compound 968 significantly suppressed tumor growth. In addition, western blotting analysis indicated that GLS1 expression was upregulated in human endometrial cancer tissues. Compound 968 may be a promising approach for the management of human endometrial cancer.

Endometrial cancer in the crossroads of modernity and immunotherapy

Frequent and with an increasing incidence in some territories, endometrial cancer is a complex disease leading to significant morbidity among affected patients. After years of research and the implementation of state-of-the-art molecular and gene assays significant breakthroughs were made. Through a better understanding of the underlying mechanisms of uterine carcinogenesis, a more precise and personalized risk stratification and the incorporation of immunotherapy, the treatment of endometrial cancer is experiencing significant improvements. This evolution, caries the genuine hope for an accurate selection of patients based on specific cancer-related characteristics, to tailor both treatment intensity and selection.

FIGO staging of endometrial cancer: 2023.

Many advances in the understanding of the pathologic and molecular features of endometrial cancer have occurred since the FIGO staging was last updated in 2009. Substantially more outcome and biological behavior data are now available regarding the several histological types. Molecular and genetic findings have accelerated since the publication of The Cancer Genome Atlas (TCGA) data and provide improved clarity on the diverse biological nature of this collection of endometrial cancers and their differing prognostic outcomes. The goals of the new staging system are to better define these prognostic groups and create substages that indicate more appropriate surgical, radiation, and systemic therapies. The FIGO Women's Cancer Committee appointed a Subcommittee on Endometrial Cancer Staging in October 2021, represented by the authors. Since then, the committee members have met frequently and reviewed new and established evidence on the treatment, prognosis, and survival of endometrial cancer. Based on these data, opportunities for improvements in the categorization and stratification of these factors were identified in each of the four stages. Data and analyses from the molecular and histological classifications performed and published in the recently developed ESGO/ESTRO/ESP guidelines were used as a template for adding the new subclassifications to the proposed molecular and histological staging system. Based on the existing evidence, the substages were defined as follows: Stage I (IA1): non-aggressive histological type of endometrial carcinoma limited to a polyp or confined to the endometrium; (IA2) non-aggressive histological types of endometrium involving less than 50% of the myometrium with no or focal lymphovascular space invasion (LVSI) as defined by WHO criteria; (IA3) low-grade endometrioid carcinomas limited to the uterus with simultaneous low-grade endometrioid ovarian involvement; (IB) non-aggressive histological types involving 50% or more of the myometrium with no LVSI or focal LVSI; (IC) aggressive histological types, i.e. serous, high-grade endometrioid, clear cell, carcinosarcomas, undifferentiated, mixed, and other unusual types without any myometrial invasion. Stage II (IIA): non-aggressive histological types that infiltrate the cervical stroma; (IIB) non-aggressive histological types that have substantial LVSI; or (IIC) aggressive histological types with any myometrial invasion. Stage III (IIIA): differentiating between adnexal versus uterine serosa infiltration; (IIIB) infiltration of vagina/parametria and pelvic peritoneal metastasis; and (IIIC) refinements for lymph node metastasis to pelvic and para-aortic lymph nodes, including micrometastasis and macrometastasis. Stage IV (IVA): locally advanced disease infiltrating the bladder or rectal mucosa; (IVB) extrapelvic peritoneal metastasis; and (IVC) distant metastasis. The performance of complete molecular classification (POLEmut, MMRd, NSMP, p53abn) is encouraged in all endometrial cancers. If the molecular subtype is known, this is recorded in the FIGO stage by the addition of "m" for molecular classification, and a subscript indicating the specific molecular subtype. When molecular classification reveals p53abn or POLEmut status in Stages I and II, this results in upstaging or downstaging of the disease (IICmp53abn or IAmPOLEmut). The updated 2023 staging of endometrial cancer includes the various histological types, tumor patterns, and molecular classification to better reflect the improved understanding of the complex nature of the several types of endometrial carcinoma and their underlying biologic behavior. The changes incorporated in the 2023 staging system should provide a more evidence-based context for treatment recommendations and for the more refined future collection of outcome and survival data.

A Fifteen Years Audit of Endometrial Cancer Referred for Adjuvant Treatment to a Tertiary Care Hospital in Northern India

Introduction: Endometrial cancer is the seventh most common cancer in women worldwide with Age Standardised Incidence Rate (ASIR) of 8.4 per lac. In Indian subcontinent, the incidence is lesser and the ASIR is 2.1/100,000 women. However, its incidence is on the steady rise in developing part of the world including India. Surgery is the primary treatment and adjuvant radiotherapy is given in patients with high-risk of recurrence and significant change has happened in the management in the last 20 years. From India limited literature is available for management practices for endometrial cancer. Aim: To assess the referral patterns, demography, staging, surgical practices, adjuvant treatment and follow-up policies for endometrial cancer in a tertiary care hospital in northern India. Materials and Methods: A retrospective cross-sectional study was done for patients having endometrial cancer treated between January 2000- December 2015 in a tertiary care hospital in northern India in January 2022. A total of 93 patients having endometrial cancer were referred for radiotherapy. For these patients, their referral patterns, demography, staging, surgical practices, adjuvant treatment and follow-up policies were analysed, retrospectively. Disease Free Survival (DFS) and Overall Survival (OS) were computed by Kaplan-Meier method. Results: The median age at presentation was 55 years. Postmenopausal vaginal bleeding was the commonest symptom 78 (83.87%). Ultrasonography 23 (24.73%) was the preferred first imaging modality. Type 1 endometroid carcinoma was 75 (80.64%) and total abdominal hysterectomy with bilateral salpingo-oophrectomy was done in 82 (88.17%). Adjuvant External Beam Radiotherapy (EBRT) with Brachytherapy (BT) was given in 61 (65.59%), EBRT alone in 7(7.52%) and BT alone given in 11 (11.83%). Median EBRT dose was 50.4 Gy. Vaginal cylinder applicator was used in 69 (95.83%) out of 72 patients receiving BT. A 6.0 Gy/# to a total of 2 fractions were given in 57 (79.16%). Median treated length of vagina was 3 cm (range 2-8 cm). Five year DFS and OS was 25% and 25% and 64% and 62% respectively in worst and best case scenario. Ten (10.75%) patients, all having high-risk had multiple visceral and local recurrence. Conclusion: In patients with endometrial cancer, total abdominal hysterectomy with bilateral salpingo-oophrectomy is commonest surgical practice with adjuvant radiotherapy in high-risk patients. In a developing country like India, assuring uniformity of treatment protocols is a challenging task.