Petra Bretová

Predictors for sentinel lymph node mapping failure using indocyanine green injection in apparent early stages of endometrial cancer: A single‐center prospective study

AbstractObjectiveThe current study aimed to analyze predictive factors of sentinel lymph node mapping failure in apparently early stages of endometrial cancer using intracervical indocyanine green injection.MethodsA single‐center prospective study was conducted between June 2019 and August 2023 at the Department of Gynecology and Obstetrics, University Hospital Brno, Czech Republic. All patients with apparently early stage (I or II according to FIGO [International Federation of Gynecology & Obstetrics] 2009) endometrial cancer, who were indicated for sentinel node biopsy were consecutively included. The injection of 4–6 mL of indocyanine green was applied superficially and deeply into cervical tissue at the 3‐ and 9‐o'clock positions. Patients' clinical data, surgical characteristics, and histopathological information were recorded. Univariable and multivariable regression analyses were applied.ResultsA total of 225 patients were eligible during the study period. Considering bilateral and unilateral failed mapping together, the only statistically significant factors for risk of failure in univariable analysis were body mass index (BMI; P = 0.036), FIGO 2009 stage (P = 0.019), and the presence of a myoma (P = 0.017). Nevertheless, when the multivariable logistic regression analysis was applied, all factors became statistically insignificant except for myoma (P = 0.031). Regarding only bilateral mapping failure, in univariable analysis, BMI (P = 0.021) and FIGO 2009 stage (P = 0.046) were significant predictors of failure. Interestingly, multivariable logistic regression analysis revealed that in addition to BMI (P = 0.007), age (P = 0.004) was also an independent predictor of bilateral failure.ConclusionsHigher BMI and age were statistically significant independent factors for bilateral sentinel node mapping failure in early‐stage endometrial cancer.

Sentinel SENECA risk factors for unsuccessful bi-lateral sentinel lymph node mapping in endometrial cancer

Our study aims to assess the risk factors associated with bi-lateral sentinel lymph node (SLN) mapping failure in endometrial cancer. The SENECA study was a retrospective multi-center international observational study that reviewed data from 2139 women with clinical stage I-to-II endometrial cancer across 64 centers in 17 countries. Between January 2021 and December 2022, patients underwent surgical treatment with SLN assessment, following the guidelines of the European Society of Gynaecological Oncology. Risk factors associated with the absence of bi-lateral mapping were analyzed using χ Among the 2139 patients, the bi-lateral lymph node detection rate was 82.7%, whereas the unilateral detection rate was 97.3%. In multi-variate analysis, 5 risk factors remained statistically associated with unsuccessful bi-lateral lymph node mapping: high-grade histology (OR 1.35, 95% CI 1.02 to 1.79, p=.03), myometrial invasion >50% (OR 1.37, 95% CI 1.07 to 1.75, p=.012), low-volume surgeon <20 cases/year (OR 2.11, 95% CI 1.55 to 2.89, p<.01), open surgical approach (OR 1.72, 95% CI 1.06 to 2.78 , p=.03), and non-indocyanine green tracer (OR 4.59, 95% CI 2.64 to 7.99, p<.01). The addition of bi-lateral pelvic lymphadenectomy and/or paraaortic lymphadenectomy to SLN biopsy caused an increased rate of intra-operative complications (2% vs 8.4%, p<.01) and all-grade post-operative complications (4.1% vs 11.2%, p<.01). Our study identifies 5 risk factors associated with unsuccessful lymph node mapping in endometrial cancer. Efforts should be made to perform this technique with indocyanine green, through minimally invasive surgery, and performed or supervised by an experienced surgeon with ≥20 endometrial cancer cases per year.

Improving pre-operative binary grading: relevance of p53 and PR expression in grade 2 endometrioid endometrial carcinoma

This study aimed to evaluate the association between pre-operative progesterone receptor (PR) and p53 expression and prognosis in pre-operative grade 2 endometrioid endometrial carcinoma compared with grade 1 and grade 3 carcinomas. Three European endometrial carcinoma cohort studies were included. Patients with pre-operative grade 2 endometrioid carcinoma and known pre-operative PR and p53 status were included (n = 400), as were patients with pre-operative grade 1 (n = 602) or grade 3 (n = 148) endometrioid carcinomas. Kaplan-Meier and Cox regression analyses were performed to analyze disease-specific and disease-free survival. Patients with pre-operative grade 2 endometrial carcinoma and wild-type p53 plus PR-positive expression showed a similar 7-year disease-specific survival to grade 1 endometrial carcinoma patients (95.8% vs 97.5%, p = .13), while the 7-year disease-specific survival of patients with grade 2 endometrial carcinoma with p53 aberrant and/or negative PR expression (83.5%) was significantly lower (p < .001). The combination of these markers was an independent prognostic factor in multivariate Cox regression analyses. The prognostic impact of pre-operative p53 and PR expression in patients with grade 2 endometrioid endometrial carcinoma supports a modified binary grading system in which grade 2 patients should be pre-operatively classified as low- or high-grade depending on p53 and PR expression.

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

SENECA study: staging endometrial cancer based on molecular classification

Management of endometrial cancer is advancing, with accurate staging crucial for guiding treatment decisions. Understanding sentinel lymph node (SLN) involvement rates across molecular subgroups is essential. To evaluate SLN involvement in early-stage (International Federation of Gynecology and Obstetrics 2009 I-II) endometrial cancer, considering molecular subtypes and new European Society of Gynaecological Oncology (ESGO) risk classification. The SENECA study retrospectively reviewed data from 2139 women with stage I-II endometrial cancer across 66 centers in 16 countries. Patients underwent surgery with SLN assessment following ESGO guidelines between January 2021 and December 2022. Molecular analysis was performed on pre-operative biopsies or hysterectomy specimens. Among the 2139 patients, the molecular subgroups were as follows: 272 (12.7%) p53 abnormal (p53abn, 1191 (55.7%) non-specific molecular profile (NSMP), 581 (27.2%) mismatch repair deficient (MMRd), 95 (4.4%) POLE mutated (POLE-mut). Tracer diffusion was detected in, at least one side, in 97.2% of the cases; with a bilateral diffusion observed in 82.7% of the cases. By ultrastaging (90.7% of the cases) or one-step nucleic acid amplification (198 (9.3%) of the cases), 205 patients were identified with affected sentinel lymph nodes, representing 9.6% of the sample. Of these, 139 (67.8%) had low-volume metastases (including micrometastases, 42.9%; and isolated tumor cells, 24.9%) while 66 (32.2%) had macrometastases. Significant differences in SLN involvement were observed between molecular subtypes, with p53abn and MMRd groups having the highest rates (12.50% and 12.40%, respectively) compared with NSMP (7.80%) and POLE-mut (6.30%), (p=0.004); (p53abn, OR=1.69 (95% CI 1.11 to 2.56), p=0.014; MMRd, OR=1.67 (95% CI 1.21 to 2.31), p=0.002). Differences were also noted among ESGO risk groups (2.84% for low-risk patients, 6.62% for intermediate-risk patients, 21.63% for high-intermediate risk patients, and 22.51% for high-risk patients; p<0.001). Our study reveals significant differences in SLN involvement among patients with early-stage endometrial cancer based on molecular subtypes. This underscores the importance of considering molecular characteristics for accurate staging and optimal management decisions.