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Objective: Real-world data for patients with endometrial cancer (EC) are limited, particularly in Latin America. We present treatment pattern findings from ECHOS-A - Endometrial Cancer Health Outcomes Study in Argentina. Materials and methods: A retrospective study using clinical data from privately insured patients with EC diagnosed from 2010 to 2019. Index (diagnosis proxy) was first date of an EC-related health term or treatment. Demographics, clinical characteristics, and FIGO staging were described. Disease progression and survival were assessed until study end, loss to follow-up, or death. Results: Of 805 patients with EC, 77.4 % (n = 623/805) received any treatment and 22.6 % (n = 182/805) received none. Among those treated, 31.8 % (n = 198/623) had first-line (1L) systemic therapy, and 45.5 % (n = 90/198) proceeded to second-line (2L) therapy. Mean follow-up was 33.6 (SD 31.8) months. Of those receiving any treatment, 87.3 % (n = 544/623) had FIGO stage data (I, 62.9 %; II, 18.6 %; III, 13.6 %; IV, 5.0 %). Treatment by class in 1L and 2L, respectively, were platinum chemotherapy, 73.7 %, 36.7 %; non-platinum chemotherapy, 73.7 %, 62.2 %; immunotherapy, 1.0 %, 11.1 %; hormone therapy, 17.7 %, 26.7 %. Carboplatin/paclitaxel was the most frequent 1L (52.5 %) and 2L (14.4 %) regimen. Mean time to progression was 14.1 (SD 16.3) and 8.8 (SD 8.3) months in 1L and 2L, respectively. Adjusted 1- to 5-year risk of progression/death was 46.5-77.5 % and 65.0-86.2 % in 1L and 2L, respectively. Conclusions: Approximately one-quarter of patients with EC received no treatment, and approximately two-thirds were not treated with 1L systemic therapy. Efforts to better understand the reasons for these treatment patterns are crucial for improving patient outcomes.

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Endometrial cancer (EC) is a heterogeneous disease with a rising incidence worldwide. The understanding of its molecular pathways has evolved substantially since The Cancer Genome Atlas (TCGA) stratified endometrial cancer into four subgroups regarding molecular features: POLE ultra-mutated, microsatellite instability (MSI) hypermutated, copy-number high with TP53 mutations, and copy-number low with microsatellite stability, also known as nonspecific molecular subtype (NSMP). More recently, the International Federation of Gynecology and Obstetrics (FIGO) updated their staging classification to include information about POLE mutation and p53 status, as the prognosis differs according to these characteristics. Other biomarkers are being identified and their prognostic and predictive role in response to therapies are being evaluated. However, the incorporation of molecular aspects into treatment decision-making is challenging. This review explores the available data and future directions on tailoring treatment based on molecular subtypes, alongside the challenges associated with their testing.

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The introduction of immune checkpoint inhibitors (ICIs) has revolutionized the treatment landscape for numerous tumor types, including cervical and endometrial cancers. Multiple ICIs against programmed cell death-1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) have demonstrated encouraging outcomes in controlled clinical studies for advanced cervical and endometrial cancers. For advanced cervical cancer, approved ICIs as second-line treatment include cemiplimab, nivolumab, and pembrolizumab as single agents. In the first-line treatment setting, options include pembrolizumab alone or in combination with bevacizumab, as well as atezolizumab combined with a backbone platinum-based chemotherapy plus bevacizumab. Additionally, for locally advanced cervical cancer, pembrolizumab is recommended alongside concurrent chemoradiotherapy. For endometrial cancer, pembrolizumab monotherapy, pembrolizumab in combination with lenvatinib, and dostarlimab are currently approved as second-line treatment options. Moreover, either dostarlimab or pembrolizumab can be added to first-line platinum-based chemotherapy for mismatch repair deficient malignancies. Although the inclusion of these agents in clinical practice has led to improved overall response rates and survival outcomes, many patients still lack benefits, possibly due to multiple intrinsic and adaptive resistance mechanisms to immunotherapy. This review aims to highlight the rationale for utilizing ICIs and their current role, while also delineating the proposed mechanisms of resistance to ICIs in cervical and endometrial cancer.

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Endometrial cancer (EC) is a significant cause of cancer-related deaths in women. MicroRNAs (miRs) play a role in cancer development, acting as oncogenes or tumor suppressors. This study evaluated the diagnostic potential of hsa-miR-185-5p and hsa-miR-191-5p in EC and their correlation with clinical and histopathological features. A cross-sectional study analyzed formalin-fixed, paraffin-embedded tissue samples from 59 patients: 18 with EC, 21 with endometrial hyperplasia (EH), 17 with normal endometrium (NE), and 3 with endometrial polyps (EPs). Quantitative reverse transcription-polymerase chain reaction and TaqMan probes were used for miR expression analysis. The Shapiro-Wilk test was used to analyze the normal distribution of the data. Subsequently, parametric or non-parametric tests were used to evaluate the associations between the expression levels of each miR and clinical parameters. Both miRs were underexpressed in some precursor and malignant lesions compared to certain NE subtypes and benign lesions. Specifically, hsa-miR-185-5p showed underexpression in grade 3 EC compared to some NE and EH subtypes (FC: -57.9 to -8.5, p < 0.05), and hsa-miR-191-5p was underexpressed in EH and EC compared to secretory endometrium and EPs (FC: -4.2 to -32.8, p < 0.05). SETD1B, TJP1, and MSI1 were common predicted target genes. In conclusion, hsa-miR-185-5p and hsa-miR-191-5p are underexpressed in EC tissues, correlating with histopathological grades, highlighting their potential as diagnostic biomarkers and their role as tumor suppressors in EC.

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OBJECTIVE: Endometrial cancer (EC) treatment changed substantially with the introduction of molecular classification. Low-middle income (LMIC) countries will face barriers to including molecular classification to guide treatment. This study aims to analyse the value of p53 immunohistochemistry to delineate adjuvant treatment in FIGO stages I and II. METHODS: Patients with EC treated between 2010 and 2016 were retrospectively evaluated. Patients included in this analysis must have reviewed FIGO stage I/II high-grade histologies (endometrioid grade 3, serous, clear cell, carcinosarcoma, mixed and undifferentiated). Samples were subjected to p53 immunohistochemistry. Recurrence-free and overall survival were analysed using the Kaplan-Meier method and log-rank test. Cox proportional hazards regression was performed for multivariable analysis. RESULTS: From 2010 to 2016, 265 patients met the inclusion criteria. Patients with aberrant p53 (71.4 %) were associated with older age (59.7 % vs 77.8 % with more than 60 years), relapse (12.5 vs 29.6 %) and death (22.2 vs 46.7 %). The pattern of relapse was not different, with most being at extrapelvic sites (55.5 % vs 62.3 % for p53 wild type and aberrant, respectively). The median overall survival was not reached versus 92.2 months for p53 wild type and aberrant, respectively (p = 0.003). In multivariate analysis, chemotherapy decreased death (p = 0.014) in p53 aberrant tumours, a benefit not seen in the wild-type cohort (p = 0.22). CONCLUSION: This retrospective analysis corroborates the finding of worse outcomes for p53 aberrant tumours in stage I/II EC and the benefit of more aggressive adjuvant treatment (systemic therapy and radiotherapy). Although not ideal as a sole molecular marker, p53 immunohistochemistry could complement the classical anatomopathological features and be part of the decision-making process with patients in LMIC.

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Introducción: El cáncer de endometrio ocupa el sexto lugar en incidencia del cáncer en mujeres. La caracterización molecular de este cáncer permite optimizar la estratificación de riesgo para mejorar el tratamiento de las pacientes. Objetivo: Determinar el perfil molecular TCGA de pacientes con cáncer de endometrio en Bogotá, D.C., Colombia. Método: Estudio descriptivo en una cohorte de pacientes con cáncer de endometrio. Las mutaciones en los exones 9 a 14 del gen POLE fueron identificadas mediante amplificación por reacción en cadena de la polimerasa, seguida de secuenciación Sanger y análisis bioinformático. La expresión de las proteínas MMR y p53 se identificó mediante inmunohistoquímica. Resultados: Se incluyeron 40 pacientes con una mediana de edad de 66 años. El 15% presentaron mutaciones en el dominio exonucleasa de POLE. El 32% de las pacientes que no presentaron mutaciones manifestaron deficiencia en el sistema MMR. El 43,47% de las pacientes sin mutaciones en POLE ni alteración del sistema MMR presentaron alteración de la proteína p53. Conclusiones: La población de cáncer de endometrio analizada presenta un perfil molecular TCGA similar a lo reportado para otras poblaciones.

Introduction: Endometrial cancer ranks sixth in cancer incidence among women. Its molecular characterization allows for a more precise risk stratification with the aim of improving patient treatment. Objective: To determine the TCGA molecular profile of patients with endometrial cancer in Bogota, Colombia. Method: A descriptive study of a cohort of patients with endometrial cancer. The expression of MMR proteins and p53 was identified through immunohistochemistry. Mutations in exons 9 to 14 of the POLE gene were identified through polymerase chain reaction amplification, followed by Sanger sequencing and bioinformatic analysis. Results: Forty patients were included in the study, with a median age of 66 years, 15% of them exhibited mutations in the exonuclease domain of POLE, while 32% of patients without mutations showed deficiency in the MMR system. Forty three percent of patients without mutations in POLE or MMR alterations showed aberrant p53 protein expression. Conclusions: The analyzed population of endometrial cancer presents a TCGA molecular profile similar to that reported for other populations.

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PURPOSE: Managing high-grade endometrial cancer in Martinique poses significant challenges. The diversity of copy number alterations in high-grade endometrial tumors, often associated with a TP53 mutation, is a key factor complicating treatment. Due to the high incidence of high-grade tumors with poor prognosis, our study aimed to characterize the molecular signature of these tumors within a cohort of 25 high-grade endometrial cases. METHODS: We conducted a comprehensive pangenomic analysis to categorize the copy number alterations involved in these tumors. Whole-Exome Sequencing (WES) and Homologous Recombination (HR) analysis were performed. The alterations obtained from the WES were classified into various signatures using the Copy Number Signatures tool available in COSMIC. RESULTS: We identified several signatures that correlated with tumor stage and disctinct prognoses. These signatures all seem to be linked to replication stress, with CCNE1 amplification identified as the primary driver of oncogenesis in over 70% of tumors analyzed. CONCLUSION: The identification of CCNE1 amplification, which is currently being explored as a therapeutic target in clinical trials, suggests new treatment strategies for high-grade endometrial cancer. This finding holds particular significance for Martinique, where access to care is challenging.

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PURPOSE: Molecular classification of endometrial cancer (EC) has become a promising information to tailor preoperatively the surgical treatment. We aimed to evaluate the rate of lymph node metastases (LNM) in patients with EC according to molecular profile. METHODS: A systematic review and meta-analysis were performed according to PRISMA guidelines by searching in two major electronic databases (PubMed and Scopus), including original articles reporting lymph node metastases according to the molecular classification of EC as categorized in the ESGO-ESMO-ESP guidelines. RESULTS: Fifteen studies enrolling 3056 patients were included. Pooled prevalence LNM when considering only patients undergoing lymph node assessment was 4% for POLE-mutated (95%CI: 0-12%), 22% for no specific molecular profile (95% CI: 9-39%), 23% for Mismatch repair-deficiency (95%CI: 10-40%) and 31% for p53-abnormal (95%CI: 24-39%). CONCLUSIONS: The presence of LNM seems to be influenced by molecular classification. P53-abnormal group presents the highest rate of nodal involvement, and POLE-mutated the lowest.

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OBJECTIVES: To investigate the impact of Three-Dimensional (3D) laparoscopy compared to traditional laparotomy on serum tumor markers and coagulation function in patients diagnosed with early-stage Endometrial Cancer (EC). METHOD: The authors retrospectively analyzed the clinical data of 75 patients diagnosed with early-stage EC and categorized them into two groups based on the surgical techniques employed. The 3D group consisted of 36 patients who underwent 3D laparoscopic surgery, while the Laparotomy group comprised 39 patients who underwent traditional laparotomy. The authors then compared the alterations in serum tumor markers and coagulation function between the two groups. RESULTS: Postoperatively, serum levels of CA125, CA199, and HE4 were notably reduced in both groups on the third day, with the levels being more diminished in the 3D group than in the Laparotomy Group (p < 0.05). Conversely, FIB levels escalated significantly in both groups on the third-day post-surgery, with a more pronounced increase in the 3D group. Additionally, PT and APTT durations were reduced and were more so in the 3D group than in the laparotomy group (p < 0.05). CONCLUSIONS: When juxtaposed with traditional laparotomy, 3D laparoscopic surgery for early-stage EC appears to be more efficacious, characterized by reduced complications, and expedited recovery. It can effectively mitigate serum tumor marker levels, attenuate the inflammatory response and damage to immune function, foster urinary function recovery, and enhance the quality of life. However, it exerts a more significant influence on the patient's coagulation parameters, necessitating meticulous prevention and treatment strategies for thromboembolic events in clinical settings.

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(1) Background: The pandemic led to significant healthcare disruptions, resulting in postponed surgeries and extended waiting times for non-urgent treatments, including hysteroscopies essential for diagnosing endometrial cancer. This study aims to formulate a risk stratification model to enhance the prioritization of hysteroscopy procedures in Brazil; (2) Methods: A case-control study was conducted at Vila Santa Catarina Hospital in São Paulo, analyzing the medical records of 2103 women who underwent hysteroscopy between March 2019 and March 2022. We used bivariate analysis and multivariate linear regression to identify risk factors associated with endometrial cancer and formulate a nomogram; (3) Results: The findings revealed a 5.5% incidence of pre-invasive and invasive endometrial disease in the study population, with an average waiting time of 120 days for hysteroscopy procedures. The main risk factors identified were hypertension, diabetes, postmenopausal bleeding, and obesity; (4) Conclusions: This research highlights the urgent need for efficient prioritization of hysteroscopy procedures in the wake of the pandemic. The developed nomogram is an innovative tool for identifying patients at higher risk of endometrial cancer, thus facilitating timely diagnosis and treatment and improving overall patient outcomes in a strained healthcare system.