Most cited article - PubMed ID 33858677
Immunohistochemical biomarkers are prognostic relevant in addition to the ESMO-ESGO-ESTRO risk classification in endometrial cancer
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
IMPORTANCE: Patients with low-grade (ie, grade 1-2) endometrial cancer (EC) are characterized by their favorable prognosis compared with patients with high-grade (ie, grade 3) EC. With the implementation of molecular profiling, the prognostic relevance of tumor grading might lose attention. As most patients present with low-grade EC and have an excellent outcome, the value of molecular profiling for these patients is unclear. OBJECTIVE: To determine the association of molecular profiling with outcomes among patients with low-grade EC. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included a multicenter international European cohort of patients diagnosed with EC between 1994 and 2018, with a median follow-up of 5.9 years. Molecular subgroups were determined by next-generation sequencing using single-molecule molecular inversion probes and by immunohistochemistry. Subsequently, tumors were classified as polymerase epsilon (POLE)-altered, microsatellite instable (MSI), tumor protein p53 (TP53)-altered, or no specific molecular profile (NSMP). Patients diagnosed with any histological subtypes and FIGO (International Federation of Gynecology and Obstetrics) stages of EC were included, but patients with early-stage EC (FIGO I-II) were only included if they had known lymph node status. Data were analyzed February 20 to June 16, 2022. EXPOSURES: Molecular testing of the 4 molecular subgroups. MAIN OUTCOMES AND MEASURES: The main outcome was disease-specific survival (DSS) within the molecular subgroups. RESULTS: A total of 393 patients with EC were included, with a median (range) age of 64.0 (31.0-86.0) years and median (range) body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 29.1 (18.0-58.3). Most patients presented with early-stage (290 patients [73.8%]) and low-grade (209 patients [53.2%]) disease. Of all patients, 33 (8.4%) had POLE-altered EC, 78 (19.8%) had MSI EC, 72 (18.3%) had TP53-altered EC, and 210 (53.4%) had NSMP EC. Across all molecular subgroups, patients with low-grade EC had superior 5-year DSS compared with those with high-grade EC, varying between 90% to 100% vs 41% to 90% (P < .001). Multivariable analysis in the entire cohort including age, tumor grade, FIGO stage, lymphovascular space invasion, and the molecular subgroups as covariates found that only high-grade (hazard ratio [HR], 4.29; 95% CI, 2.15-8.53; P < .001), TP53-altered (HR, 1.76; 95% CI, 1.04-2.95; P = .03), and FIGO stage III or IV (HR, 4.26; 95% CI, 2.50-7.26; P < .001) disease were independently associated with reduced DSS. CONCLUSIONS AND RELEVANCE: This cohort study found that patients with low-grade EC had an excellent prognosis independent of molecular subgroup. These findings do not support routine molecular profiling in patients with low-grade EC, and they demonstrate the importance of primary diagnostic tumor grading and selective profiling in low-grade EC to increase cost-effectiveness.
- MeSH
- Carcinoma, Endometrioid * pathology MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Endometrial Neoplasms * MeSH
- Prognosis MeSH
- Retrospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
BACKGROUND: Endometrial cancer is the most common gynecological malignancy in developed countries with no screening available. There is still a tendency to provide invasive bioptic verification in asymptomatic women with abnormal ultrasound findings to diagnose carcinoma in a preclinical phase; even though, it is not supported by European guidelines. Our goal was to determine DFS (disease-free survival), OS (overall survival), and DSS (disease-specific survival) differences between symptom-free and symptomatic (bleeding, or spotting) endometrial cancer patients with similar stage and tumor/clinical characteristics. METHODS: All of our patients with endometrial cancer following surgical treatment between 2006 and 2019 were assessed, evaluating risk factors for recurrence and death while focusing on bleeding using univariable and multivariable analysis. RESULTS: 625 patients meeting the inclusion criteria were divided into asymptomatic (n = 144, 23%) and symptomatic (n = 481, 77%) groups. The median follow-up was 3.6 years. Using univariable analysis, symptomatic patients had a three times higher risk of recurrence (HR 3.1 (95% Cl 1.24-7.77), p = 0.016). OS (HR 1.35 (0.84-2.19), p = 0.219) and DSS (HR 1.66 (0.64-4.28), p = 0.3) were slightly worse without reaching statistical significance. In our multivariable analysis, symptomatology was deemed completely insignificant in all monitored parameters (DFS: HR 2.03 (0.79-5.24), p = 0.144; OS: HR 0.72 (0.43-1.21), p = 0.216). CONCLUSIONS: The symptomatic endometrial cancer patients risk factor of earlier recurrence and death is insignificantly higher when compared with the asymptomatic cohort. However, multivariable analysis verifies that prognosis worsens with other clinically relevant parameters, not by symptomatology itself. In terms of survival outcome in EC patients, we recognized symptomatology as a non-significant marker for the patient's prognosis.
- Keywords
- endometrial cancer, postmenopausal bleeding, prognosis,
- Publication type
- Journal Article MeSH