Vit Weinberger

The cutoff for estrogen and progesterone receptor expression in endometrial cancer revisited: a European Network for Individualized Treatment of Endometrial Cancer collaboration study

There is no consensus on the cutoff for positivity of estrogen receptor (ER) and progesterone receptor (PR) in endometrial cancer (EC). Therefore, we determined the cutoff value for ER and PR expression with the strongest prognostic impact on the outcome. Immunohistochemical expression of ER and PR was scored as a percentage of positive EC cell nuclei. Cutoff values were related to disease-specific survival (DSS) and disease-free survival (DFS) using sensitivity, specificity, and multivariable regression analysis. The results were validated in an independent cohort. The study cohort (n = 527) included 82% of grade 1-2 and 18% of grade 3 EC. Specificity for DSS and DFS was highest for the cutoff values of 1-30%. Sensitivity was highest for the cutoff values of 80-90%. ER and PR expression were independent markers for DSS at cutoff values of 10% and 80%. Consequently, three subgroups with distinct clinical outcomes were identified: 0-10% of ER/PR expression with, unfavorable outcome (5-year DSS = 75.9-83.3%); 20-80% of ER/PR expression with, intermediate outcome (5-year DSS = 93.0-93.9%); and 90-100% of ER/PR expression with, favorable outcome (5-year DSS = 97.8-100%). The association between ER/PR subgroups and outcomes was confirmed in the validation cohort (n = 265). We propose classification of ER and PR expression based on a high-risk (0-10%), intermediate-risk (20-80%), and low-risk (90-100%) group.

ENDORISK-2: A personalized Bayesian network for preoperative risk stratification in endometrial cancer, integrating molecular classification and preoperative myometrial invasion assessment

ENDORISK is a Bayesian network that can assist in preoperative risk estimation of lymph node metastasis (LNM) risk in endometrial cancer (EC) with consistent performance in external validations. To reflect state of the art care, ENDORISK was optimized by integrating molecular classification and preoperative assessment of myometrial invasion (MI). Variables for POLE, MSI, and preoperative assessment of MI, either by expert transvaginal ultrasound or pelvic magnetic resonance imaging (MRI), were added to develop ENDORISK-2. The p53 biomarker, part of the molecular classification, was already included in ENDORISK. External validation of ENDORISK-2 for LNM prediction was performed in two independent cohorts from: Brno (CZ), (n = 581) and Tübingen (DE), (n = 247). ENDORISK-2 yielded AUCs of 0·85 (95 % CI 0·80-0·90) (CZ) and 0·86 (95 % CI 0·77-0·96) (DE) for predicting LNM. In patients with low-grade histology, 83 % (CZ) and 89 % (DE) were estimated having less than 10 % risk of LNM, with false negative rates (FNR) of 4·3 % (CZ) and 2·2 % (DE). The previously defined set of minimally required variables, i.e.: preoperative tumor grade, three of the four immunohistochemical (IHC) markers, and one clinical marker, could be interchanged with the new variables, with comparable validation metrics, including AUC values of 0·79-0·87 for LNM prediction. Incorporation of molecular data and preoperative MI improved the flexibility of ENDORISK with comparable diagnostic accuracy for estimating LNM as when based on low-cost immunohistochemical biomarkers. In addition, the high diagnostic accuracy in patients with low-grade EC demonstrates how ENDORISK-2 could aid clinicians in identifying patients in whom surgical lymph node assessment may safely be omitted. These results underline its power for clinical use in both high and low resource countries.

Low-volume regional lymph node metastasis in endometrial cancer – 2024 update

Due to the implementation of sentinel lymph node ultrastaging, the prevalence of isolated tumor cells and micrometastases have increased. This literature review comprises of articles published between January 2019 and September 2024 aiming at low-volume metastases in regional lymph nodes, their prognosis, and links to molecular classification. Micrometastases are currently considered as having metastatic lymph node involvement; however, they have a better prognosis than macrometastases. Accordingly, therapy is tailored. In contrast, isolated tumor cell presence is not considered metastatic involvement according to International Federation of Gynecology and Obstetrics (FIGO) 2023 staging and does not affect the therapeutic procedure because their significant prognostic importance has not been proven so far. Key words: low-volume metastasis – endometrial cancer – ultrastaging – isolated tumor cells – micrometastases – sentinel lymph node

Risk of atrial fibrillation in endometrial cancer patients

Objective: The study aimed to define atrial fibrillation frequency in endometrial cancer patients, identify risk factors, and propose preventive steps for early detection and treatment leading to decreasing cardiovascular risk. Secondly, we aimed to highlight this topic by presenting a systematic literature review. Methodology: Retrospective analysis of endometrial cancer patients treated at the Department of Gynecology and Obstetrics at University Hospital Brno between 2006 and 2023 complemented by a systematic literature review. Results: The incidence of atrial fibrillation in endometrial cancer patients in our study group (1,101 patients) was 10.4%. Overall, 27% of patients suffered from obesity, hypertension, and diabetes, 26% from both hypertension and obesity, and 10% from diabetes and obesity. The incidence of other risk factors and their combination was less than 10%. Conclusion: Endometrial cancer patients are at a higher risk of developing atrial fibrillation compared with the general population. The risk is enhanced by the presence of other common risk factors such as hypertension, diabetes, and obesity. Key words: endometrial cancer – atrial fibrillation – cardiovascular dis ease – obesity – hypertension – diabetes mellitus

Ultrasound finding of endometrial polyp and factors increasing risk of malignancy

This article presents a comprehensive review of factors that increase the risk of malignancy in ultrasound findings of an endometrial polyp. We collected original studies, reviews, and meta-analyses that dealt with the topic of endometrial polyps and the risk of developing endometrial cancer. Each presumed risk factor was analysed individually. According to searched studies, abnormal uterine bleeding, old age, and body mass index are valid risk factors for developing endometrial cancer in endometrial polyps. Lynch syndrome patients are also in a high-risk group for endometrial cancer. On the other hand, the number of polyps, their size, diabetes mellitus, hypertension, and positive family history are factors with inconclusive results. There are either not enough data or different results among several studies. Key words: endometrial polyp – risk factors – endometrial carcinoma – polyp size – tamoxifen – abnormal uterine bleeding