The International Federation of Gynaecology and Obstetrics (FIGO) introduced a new staging system for endometrial carcinoma FIGO 2023 in June 2023. The new staging system differs significantly from previous versions by incorporating other non-anatomical parameters (histological type of tumour, tumour grade and the presence of massive lymphovascular space involvement as well as the molecular classification of the tumour). The FIGO 2023 staging system enhances the accuracy of prognostic assessments for patients at a specific stage with better options for targeted treatment. Another objective was to synchronise staging as much as possible with the European oncogynaecological ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma established in 2021. However, several changes are controversial. Routine molecular classification of endometrial carcinomas is not yet commonly available in most countries of the world. Another limitation of the FIGO 2023 staging system of endometrial cancer is the inclusion of variables whose definitions are still evolving, as well as variables that are subject to considerable interobserver variability in their assessment. Advantages, controversies, and limitations for clinical practice of the new FIGO 2023 endometrial cancer staging system are discussed.

Im Juni 2023 hat die Internationale Vereinigung für Gynäkologie und Geburtshilfe (FIGO) ein neues Staging-System für das Endometriumkarzinom – FIGO 2023 – eingeführt. Das neue Staging-System unterscheidet sich signifikant von früheren Versionen, da nun auch andere nicht anatomische Parameter (z. B. histologischer Tumortyp, Tumorgrad, ausgedehnter Befall des lymphatischen Raums sowie die molekulare Klassifikation von Tumoren) einbezogen wurden. Das FIGO-2023-Staging-System verbessert die prognostische Genauigkeit bei Patientinnen in einem bestimmten Tumorstadium mit einer besseren Auswahl an gezielten Behandlungsmöglichkeiten. Zweck des neuen Systems ist es auch, das FIGO-Staging weitmöglichst mit dem Staging der gynäkologisch-onkologischen Europäischen Leitlinien der ESGO/ESTRO/ESP, die im Jahre 2021 für das Management von Patientinnen mit Endometriumkarzinom aufgestellt wurden, in Einklang zu bringen. Allerdings werden mehrere Änderungen immer noch kontrovers diskutiert. So ist in den meisten Ländern der Welt die routinemäßige molekulare Klassifikation von Endometriumkarzinomen nicht allgemein üblich oder erhältlich. Eine weitere Einschränkung des FIGO-2023-Staging-Systems für das Endometriumkarzinom ist die Einbeziehung von Variablen, deren Definitionen noch im Entstehen begriffen sind, bzw. von Variablen, die eine erhebliche Interobserver-Variabilität aufweisen. Die Vorteile, Kontroversen und Einschränkungen des neuen FIGO-2023-Staging-Systems in der klinischen Praxis werden hier diskutiert.

• Keywords
• ESGO, ESP, ESTRO, FIGO 2023, controversies, endometrial cancer, molecular classification, staging, staging system,
• Publication type
• Journal Article MeSH

Mismatch repair-deficient (dMMR) endometrial cancer (EC) is an inflamed phenotype with poor outcomes when meeting high-risk criteria and limited treatment options in the adjuvant setting. We report protocol-prespecified subgroup analysis of patients with dMMR tumors from the phase III ENGOT-en11/GOG-3053/KEYNOTE-B21 study (ClinicalTrials.gov identifier: NCT04634877) in newly diagnosed, high-risk EC after surgery with curative intent. Patients were randomly assigned to pembrolizumab 200 mg or placebo (six cycles) plus carboplatin-paclitaxel (four to six cycles) once every 3 weeks, then pembrolizumab 400 mg or placebo once every 6 weeks (six cycles), respectively. MMR status was a stratification factor. Patients received radiotherapy at investigator discretion. Investigator-assessed disease-free survival (DFS) was a primary end point. No formal hypothesis testing was performed for subgroup analysis. In the intention-to-treat population, 141 patients in the pembrolizumab arm and 140 in the placebo arm had dMMR tumors. At this interim analysis, hazard ratio for DFS favored pembrolizumab (0.31 [95% CI, 0.14 to 0.69]); median DFS was not reached in either group. Two-year DFS rates were 92.4% (95% CI, 84.4 to 96.4) and 80.2% (95% CI, 70.8 to 86.9), respectively. No new safety signals occurred. Longer-term follow-up of outcomes will be evaluated at final analysis. Preplanned subgroup analysis on the basis of the study's stratification factors suggests that pembrolizumab plus chemotherapy improves DFS and is clinically relevant for patients with dMMR tumors in the curative-intent setting.

• MeSH
• Chemotherapy, Adjuvant MeSH
• Adult MeSH
• Double-Blind Method MeSH
• Antibodies, Monoclonal, Humanized * administration & dosage   adverse effects   therapeutic use   MeSH
• Carboplatin administration & dosage   adverse effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Endometrial Neoplasms * drug therapy   genetics   pathology   radiotherapy   MeSH
• DNA Mismatch Repair * MeSH
• Paclitaxel administration & dosage   adverse effects   MeSH
• Antineoplastic Combined Chemotherapy Protocols * therapeutic use   adverse effects   MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Antibodies, Monoclonal, Humanized * MeSH
• Carboplatin MeSH
• Paclitaxel MeSH
• pembrolizumab MeSH Browser

BACKGROUND: Patients with advanced/recurrent endometrial cancer have a poor prognosis and limited treatment options. Biomarkers such as tumor protein 53 (TP53) in endometrial cancer can integrate novel strategies for improved and individualized treatment that could impact patient outcomes. In an exploratory analysis of the phase III ENGOT-EN5/GOG-3055/SIENDO study of selinexor maintenance monotherapy 80 mg in advanced/recurrent endometrial cancer, a pre-specified subgroup of patients with TP53 wild type (wt) endometrial cancer showed preliminary activity at long-term follow-up with a generally manageable safety profile (median progression-free survival 27.4 months vs 5.2 months placebo, HR=0.41). PRIMARY OBJECTIVE: To evaluate the efficacy of selinexor compared with placebo as maintenance therapy in patients with advanced or recurrent TP53wt endometrial cancer. STUDY HYPOTHESIS: Selinexor administered at 60 mg weekly as maintenance therapy will show manageable safety and maintain efficacy in patients with TP53wt advanced/recurrent endometrial cancer after systemic therapy versus placebo. TRIAL DESIGN: This is a prospective, multicenter, double-blind, placebo-controlled, randomized phase III study designed to evaluate the efficacy and safety of selinexor as a maintenance therapy in patients with advanced or recurrent TP53wt endometrial cancer. MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients must have histologically confirmed endometrial cancer, TP53wt confirmed by next-generation sequencing, completed at least 12 weeks of platinum-based therapy with or without immunotherapy, with confirmed partial response or complete response, and primary Stage IV disease or at first relapse. PRIMARY ENDPOINT: The primary endpoint is investigator-assessed progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in the intent-to-treat population. SAMPLE SIZE: A total of 220 patients will be enrolled. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual is expected to be completed in 2024 with presentation of results in 2025. TRIAL REGISTRATION: NCT05611931.

• Keywords
• Uterine Cancer,
• MeSH
• Double-Blind Method MeSH
• Hydrazines * administration & dosage   therapeutic use   MeSH
• Clinical Trials, Phase III as Topic MeSH
• Humans MeSH
• Neoplasm Recurrence, Local * drug therapy   pathology   MeSH
• Multicenter Studies as Topic MeSH
• Tumor Suppressor Protein p53 genetics   MeSH
• Endometrial Neoplasms * drug therapy   pathology   MeSH
• Randomized Controlled Trials as Topic MeSH
• Triazoles * administration & dosage   MeSH
• Maintenance Chemotherapy methods   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial Protocol MeSH
• Names of Substances
• Hydrazines * MeSH
• Tumor Suppressor Protein p53 MeSH
• selinexor MeSH Browser
• TP53 protein, human MeSH Browser
• Triazoles * MeSH

BACKGROUND: Response to hormonal therapy in advanced and recurrent endometrial cancer (EC) can be predicted by oestrogen and progesterone receptor immunohistochemical (ER/PR-IHC) expression, with response rates of 60% in PR-IHC > 50% cases. ER/PR-IHC can vary by tumour location and is frequently lost with tumour progression. Therefore, we explored the relationship between ER/PR-IHC expression and tumour location in EC. METHODS: Pre-treatment tumour biopsies from 6 different sites of 80 cases treated with hormonal therapy were analysed for ER/PR-IHC expression and classified into categories 0-10%, 10-50%, and >50%. The ER pathway activity score (ERPAS) was determined based on mRNA levels of ER-related target genes, reflecting the actual activity of the ER receptor. RESULTS: There was a trend towards lower PR-IHC (33% had PR > 50%) and ERPAS (27% had ERPAS > 15) in lymphogenic metastases compared to other locations (p = 0.074). Hematogenous and intra-abdominal metastases appeared to have high ER/PR-IHC and ERPAS (85% and 89% ER-IHC > 50%; 64% and 78% PR-IHC > 50%; 60% and 71% ERPAS > 15, not significant). Tumour grade and previous radiotherapy did not affect ER/PR-IHC or ERPAS. CONCLUSIONS: A trend towards lower PR-IHC and ERPAS was observed in lymphogenic sites. Verification in larger cohorts is needed to confirm these findings, which may have implications for the use of hormonal therapy in the future.

• Keywords
• endometrial cancer, hormone receptor, tumour location,
• Publication type
• Journal Article MeSH