Early Stage Endometrial Cancer Patients Research Articles

Predicting the Risk of nOdal disease with histological and Molecular features in Endometrial cancer: the prospective PROME trial.

To assess the role of histopathological and molecular features in predicting the risk of nodal metastases in apparent early-stage endometrial cancer patients undergoing sentinel node mapping. This is a prospective trial. Consecutive patients with apparent early-stage endometrial cancer, undergoing laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and sentinel node mapping, were enrolled. Histological and molecular features were used to predict the node positivity. Charts of 223 apparent early-stage endometrial cancer patients were included in this study. Four (1.8%) patients were excluded from this study due to the lack of data about molecular features. Additionally, nine (4%) patients did not meet the inclusion criteria (due to the presence of peritoneal carcinomatosis or bulky nodes (the presence of p53 abnormality correlated with the presence of advanced stage disease (p<0.001)). The study population included 178 (84.8%) and 32 (15.2%) patients with endometrioid and non-endometrioid endometrial cancer, respectively. According to pathological uterine risk factors, 93 (44.3%), 45 (21.4%), 40 (19.1%), and 32 (15.2%) were classified as low, intermediate, intermediate-high, and high-risk, respectively. Using the surrogate molecular classification, 10 (4.8%), 42 (20%), 57 (27.1%), and 101 (48.1%) were included in the POLE mutated, p53 abnormal, MMRd/MSI-H, and NSMP, respectively. Overall, 41 (19.5%) patients were detected with positive nodes. Molecular features were not associated with the risk of having nodal metastases (OR 1.03, 95% CI 0.21 to 5.05, p=0.969 for POLE mutated; OR 0.788, 95% CI 0.32 to 1.98, p=0.602 for p53 abnormal; OR 1.14, 95% CI 0.53 to 2.42, p=0.733 for MMRd/MSI-H). At multivariable analysis, only deep myometrial invasion (OR 3.318, 95% CI 1.357 to 8.150, p=0.009) and lymphovascular space invasion (OR 6.584, 95% CI 2.663 to 16.279, p<0.001) correlated with the increased risk of positive nodes. Our data suggest that molecular classification does not seem useful to tailor the need of nodal dissection in apparent early-stage endometrial cancer. p53 abnormality predicts the risk of having advanced disease at presentation. Further external validation is needed. NCT05793333.

A Comparative Cohort Study of Laparoscopy Versus Laparotomy for the Treatment of Iranian Endometrial Cancer Patients

Background: In recent decades, laparoscopy and robotic surgery are mostly used for the treatment of endometrial cancer. Laparoscopic surgery's popularity has grown due to rapid postoperative recovery and reduced post-surgical morbidity and complications compared with open surgery. Objectives: This study aimed to compare laparoscopic surgery and laparotomy in terms of their advantages and disadvantages for treating early-stage endometrial cancer in a population of Iranian patients in a referral center of gyneco-oncology. Methods: In this cohort study at Imam Hossein Medical Center in Tehran, Iran, from 2019 to 2022, early-stage endometrial cancer patients were included. Advanced disease, patients with medical comorbidity not suitable for laparoscopy, previous surgery for endometrial cancer, and prior chemotherapy or radiotherapy for treatment of the endometrial cancer were excluded from the study. The study compared two groups regarding operative findings, including FIGO stage, grade, postoperative complications, and hospitalization days. Results: The study included 17 patients in the laparoscopic group with a mean age of 56(+ 12.5) years old and 44 patients in the laparotomy group with a mean age of 57(+ 10.2) years old. Two groups were well-matched in terms of body mass index and menopausal status. The median intraoperative blood loss was significantly in terms of statistical less in the laparoscopic group (200 ml versus 500 ml, P = 0.001). Four (23.5%) patients in the laparoscopic group needed intraoperative blood transfusion versus 22 (50.0%) in the laparotomy group, P = 0.061. Hospital stay days were shorter in the laparoscopic group, with a median of three versus six days (P &lt; 0.001). Conclusions: In conclusion, the minimally invasive operation caused less blood loss, hospital stay, and blood transfusion in comparison to laparotomy in Iranian endometrial cancer patients, confirming the preferred method of laparoscopy in these patients.

Prognostic values of tumor size and location in early stage endometrial cancer patients who received radiotherapy.

To investigate the correlation between tumor size, tumor location, and prognosis in patients with early-stage endometrial cancer (EC) receiving adjuvant radiotherapy. Data of patients who had been treated for stage I-II EC from March 1999 to September 2017 in 13 tertiary hospitals in China was screened. Cox regression analysis was performed to investigate associations between tumor size, tumor location, and other clinical or pathological factors with cancer-specific survival (CSS) and distant metastasis failure-free survival (DMFS). The relationship between tumor size as a continuous variable and prognosis was demonstrated by restricted cubic splines. Prognostic models were constructed as nomograms and evaluated by Harrell's C-index, calibration curves and receiver operating characteristic (ROC) curves. The study cohort comprised 805 patients with a median follow-up of 61 months and a median tumor size of 3.0 cm (range 0.2-15.0 cm). Lower uterine segment involvement (LUSI) was found in 243 patients (30.2%). Tumor size and LUSI were identified to be independent prognostic factors for CSS. Further, tumor size was an independent predictor of DMFS. A broadly positive relationship between poor survival and tumor size as a continuous variable was visualized in terms of hazard ratios. Nomograms constructed and evaluated for CSS and DMFS had satisfactory calibration curves and C-indexes of 0.847 and 0.716, respectively. The area under the ROC curves for 3- and 5-year ROC ranged from 0.718 to 0.890. Tumor size and LUSI are independent prognostic factors in early-stage EC patients who have received radiotherapy. Integrating these variables into prognostic models would improve predictive ability.

The prognostic value of co-expression of stemness markers CD44 and CD133 in endometrial cancer.

The purpose of this study was to investigate the correlation between stemness markers (CD44 and CD133) and clinical pathological features, and to further explore the prognostic value of co-expression of CD44 & CD133 in endometrial cancer (EC). Clinical data of stage I-III EC patients who underwent initial surgical treatment at two large tertiary medical centers from 2015 to 2020 were retrospectively collected. Cohen's kappa coefficient was used to show the consistency of the expression between CD44 and CD133. The correlation between co-expression of CD44 & CD133 and prognosis of EC patients was explored using univariate and multivariate Cox regression analysis. Then, the prognosis models for early-stage (stage I-II) EC patients were constructed. Finally, stratified analysis was performed for EC patients in high-intermediate-risk and high-risk groups, Kaplan-Meier analysis was used to compare the survival differences between patients with and without adjuvant therapy in different co-expression states (low expression, mixed expression, high expression) of CD44 & CD133. A total of 1168 EC patients were included in this study. The consistency of the expression between CD44 and CD133 was 70.5%, the kappa coefficient was 0.384. High expression of CD44 & CD133 was associated with early FIGO stage (P=0.017), superficial myometrial invasion (P=0.017), and negative lymphatic vessel space invasion (P=0.017). Cox regression analysis showed that the co-expression of CD44 & CD133 was significantly correlated with the prognosis of early-stage (stage I-II) patients (P=0.001 for recurrence and P=0.005 for death). Based on this, the nomogram models were successfully constructed to predict the prognosis of early-stage EC patients. Meanwhile, Kaplan-Meier analysis showed that patients with adjuvant therapy had a better overall prognosis than those without adjuvant therapy in high-intermediate-risk and high-risk groups. However, there was no statistically significant difference in survival between patients with and without adjuvant therapy in high expression of CD44 & CD133 group (P=0.681 for recurrence, P=0.621 for death). High expression of CD44 & CD133 was closely related to the adverse prognosis of early-stage EC patients. Meanwhile, patients with high expression of CD44 & CD133 may not be able to achieve significant survival benefits from adjuvant therapy.

Efficacy of fertility-sparing treatment with LNG-IUS is associated with different ProMisE subtypes of endometrial carcinoma or atypical endometrial hyperplasia.

To determine whether proactive molecular risk classifier for endometrial cancer (ProMisE) could be used to assess the prognosis of patients with atypical endometrial hyperplasia (AEH) or early-stage endometrial cancer (EC) treated with levonorgestrel-releasing intrauterine system (LNG-IUS). A retrospective cohort study was conducted among 93 AEH or early-stage EC patients who received LNG-IUS to preserve fertility . By immunohistochemistry and gene sequencing, 4 subtypes of ProMisE were identified (p53 wild type [p53 wt], mismatch repair-deficient [MMRd], p53-abnormal, and POLE-mutated). The primary outcome was the time to complete response (CR) after LNG-IUS therapy. Secondary outcomes included the recurrence rate after CR and success rate of conception. Among the 93 patients, 15 (16.1%) were classified as MMRd, 6 (6.5%) as POLE-mutated, 5 (5.4%) as p53-abnormal, and 67 (72.0%) as p53 wt. Comparison of serum cancer antigen 125, family history of tumor, and positive rates of programmed cell death 1 ligand 1 protein and Ki67 protein in 4 groups showed statistically significant differences (p<0.05). Patients with the p53-abnormal subtype had the lowest overall CR rate (40%) and the highest recurrence rate (2/2). Patients with POLE-mutated subtype had the best prognosis, and all 6 patients achieved CR. When patients achieved complete remission, assisted reproductive technology was more likely to help them conceive than natural conception (p<0.05). Patients with early-stage EC or AEH who are more likely to benefit from fertility-sparing treatment can be identified using ProMisE classifier. Patients with POLE-mutated are suitable for fertility-sparing treatment with LNG-IUS.

Predictors of recurrence and survival in lymphovascular space invasion negative early-stage endometrioid endometrial cancer patients.

The purpose of this study was to assess prognostic factors correlated with recurrence and decreased oncologic outcomes, as well as the role of adjuvant treatment on survival in women with stage I and II endometrioid endometrial cancer without lymphovascular space invasion (LVSI). Patients with LVSI negative, early-stage endometrioid endometrial cancer patients were retrospectively reviewed. Multivariable logistic regression models were used for identifying predictors of recurrence. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, and survival curves were compared by log-rank test. Univariable and multivariable analyses were performed to establish factors affecting OS and DFS. Hazard ratios with 95% confidence intervals were calculated. A total of 289 patients were included, with a mean age of 58 years and the median surveillance time of 45 (6-147) months. The majority of the patients (54%) had grade 1 tumors. Adjuvant therapy was administered to 68 (23.5%). A total of 13 (4.5%) recurred with median time to recurrence of 52 months. Patients receiving adjuvant treatment were more likely to recur (p=0.015), and grade was the only independent predictor of recurrence (p=0.029). Five-year OS and DFS were 95.8% and 97.9%, respectively. While tumor size (p=0.018) and grade 3 histology (p=0.045) were related with shorter DFS, age (p<0.001) was the only related factor for decreased OS. Recurrence rate was low among LVSI negative, early-stage endometrioid endometrial cancer patients. Although recurrences were seen more frequently in patients who received adjuvant treatment, it wasn't an independent prognostic factor. Neither recurrence nor adverse uterine risk factors were associated with shorter OS. While age was the only prognostic factor for decreased OS, grade 3 histology and tumor size were associated with decreased DFS.

Image-guided high-dose-rate brachytherapy as the method of choice in medically inoperable early-stage endometrial cancer patients

PurposeAbout 3–9% of patients with endometrial cancer are unable to undergo surgery due to medical comorbidities, including morbid obesity, or age-related frailty syndrome. An alternative curative option is irradiation. The aim of this prospective study was to evaluate clinical outcomes of high-dose-rate intracavitary brachytherapy (HDR-ICBT) treatment in such patients. Materials and methodsSeventy-eight patients with FIGO stage I-II endometrial cancer disqualified from surgery were treated with HDR-ICBT with 45–52,5 Gy prescribed to high-risk clinical target volume (HR-CTV) in 5–9 fractions given once a week. All fractions were planned using computed tomography (CT) scans. ResultsThe median follow-up time was 67 months. Median age was 79 years (range: 42–93 years). Median body mass index (BMI) was 39,1 kg/m2 (range: 24,2–68 kg/m2). We observed no statistically significant impact of BMI ≥ 40 on overall survival (OS) or prgression free survival (PFS). The 3- and 5-year OS for the whole population were 69% and 55%, respectively. The impact of high risk features (FIGO II, grade 3 or type 2 cancer) on OS was significant (p = 0,049). The 5-year cumulative incidence of local failure, distant metastases and non-cancer death were 12,9% [95% CI: 5,4%–20,5%], 6,4% [95% CI: 0,9%–11,9%], 33,1% [95% CI: 22,3%–43,9%], respectively. The 5-year risk of cancer and non-cancer death were 9% (95% CI: 3%–16%) and 36% (95% CI: 25%–47%), respectively. We observed G1 vaginal apex stenosis only. ConclusionsCT-guided HDR-ICBT is a feasible and safe management of FIGO stage I endometrial cancer in obese and elderly patients. The survival outcome of the treated group is influenced more by associated comorbidities than by the progression of endometrial cancer.

Data-independent acquisition for proteomic applications in early-stage endometrial cancer progression.

Most endometrial cancer (EC) patients are diagnosed at an early-stage (FIGO stage I or II), with a favorable prognosis. However, some high-grade, early-stage EC patients have unexpected recurrences and undesirable results, the molecular alterations that underlie these tumors are far from being fully understood. Our goal was to use proteome analysis to examine dysregulated pathways in this specific subgroup of EC. We used data-independent acquisition (DIA) quantitative proteomics to analyze cancer and matched paracancerous tissues from 20 EC patients (10 high-grade and 10 low-grade). Immunohistochemistry (IHC) analysis was used to validate protein expression of six hub genes. In total, 7107 proteins were quantified, while 225 downregulated and 366 upregulated proteins in high-grade cancer tissues, 130 downregulated and 413 upregulated proteins in high-grade paracancerous tissues. The pathway associated with oxidative phosphorylation (OXPHOS) was upregulated and have similar expression patterns in high-grade EC tissues and matched paracancerous tissues. OXPHOS-related protein, ATP5F1D showed the best classification and diagnostic ability in distinguishing high-grade from low-grade EC. In both cancer and paracancerous tissues, double-label immunofluorescence demonstrated ITGA4 and COL4A1 co-localized at the basal membrane. Our present works elucidate that metabolism reprogramming is associated with high-grade, early-stage EC, particularly OXPHOS is upregulated. Noticeably, the paracancerous tissues have undergone molecular changes similar to cancer tissues, maybe they have signal exchange via secreted proteins (ITGA4 and COL4A1). The upregulation of OXPHOS-related proteins may be the potential biomarker for EC diagnosis, and targeting OXPHOS metabolism might be an effective treatment for high-grade, early-stage EC.

Exploring the Prognostic and Predictive Roles of Ki-67 in Endometrial Cancer

Background: Up to now, endometrial cancer (EC) treatments are mainly represented by surgery followed by adjuvant chemotherapy or radiotherapy. The updated guidelines give a 2A recommendation for the use of hormone therapy only in advanced low-grade ECs, underlying the need for more data on the role of hormone therapy in the adjuvant setting. Methods: The clinicopathological data of 158 early-stage EC patients was retrospectively collected. A Ki-67 cut-off value of 40% was established based on literature data. Disease-free survival (DFS) and Overall survival (OS) were evaluated. Results: Results: Multivariate analysis of DFS and OS showed a significantly increased risk of progression in patients with &gt;40% Ki-67 [HR = 3.13 (95% CI; 1.35–7.14); p = 0.007] and a significantly higher relative risk of death [HR = 3.70 (95% CI; 1.69–8.33); p = 0.001]. The predictive role of the Ki-67 index was highlighted by the clinical benefit of adjuvant hormone in patients with high Ki-67. Conclusions: Our results suggest a positive role of the Ki-67 index as a prognostic and potentially predictive marker in EC, although further studies are warranted to reach a definitive conclusion.

Prophylactic anticoagulation after minimally invasive hysterectomy for endometrial cancer: a cost-effectiveness analysis

ObjectiveTo determine our institutional rate of venous thromboembolism (VTE) following minimally invasive surgery for endometrial cancer and to perform a cost-effectiveness analysis of extended prophylactic anticoagulation after minimally invasive staging...

Enhanced Risk Stratification in Early-Stage Endometrial Cancer: Integrating POLE through Droplet Digital PCR and L1CAM.

In order to enhance risk stratification in early-stage endometrial cancer (EC), we conducted molecular classification using surrogate markers, including the POLE droplet digital polymerase chain reaction (ddPCR) and L1CAM immunohistochemistry (IHC). We analyzed archival tumor tissue from 183 early-stage EC patients. POLE pathogenic mutations of P286R, V411L, S297F, A456P, and S459F within exons 9, 13, and 14 were detected using a ddPCR, while the mismatch repair (MMR) status was determined by MMR protein IHC and MSI tests. Additionally, we conducted IHC for p53 and L1CAM. The 183 ECs were categorized into four subgroups: POLE-mutated (15.9%), MMR-deficient (29.0%), p53-abnormal (8.7%), and non-specific molecular profile (NSMP, 46.4%). We further subcategorized the NSMP subgroup into NSMP-L1CAMneg (41.5%) and NSMP-L1CAMpos (4.9%), which we refer to as the molecular L1CAM classification. The molecular L1CAM classification was an independent prognostic factor for recurrence-free survival (RFS) and overall survival (OS) (p < 0.001, each). Integrating molecular L1CAM classification can enhance risk stratification in early-stage EC, providing valuable prognostic information to guide treatment decisions and improve patient outcomes. POLE ddPCR might be a cost-effective and easy-to-perform test as an alternative to POLE NGS.

Treatment outcomes of early-stage endometrial cancer patients: A propensity score matching of vaginal brachytherapy versus pelvic radiotherapy.

This study aimed to report the treatment outcomes of radiation therapy for early-stage endometrial cancer patients. In addition, this study intended to identify high-risk factors that require pelvic radiotherapy (PRT) in addition to vaginal brachytherapy (VBT) for intermediate-risk endometrial cancer patients. Patients with early-stage endometrial cancer receiving postoperative VBT alone or with PRT were included. Propensity score matching was used to balance the two study groups. The primary endpoint was locoregional recurrence (LRR). Age-adjusted Charlson comorbidity index and substantial lymphovascular space invasion were selected for subgroup analyses to identify the benefits of PRT over VBT alone. From 2005 to 2017, a total of 288 patients underwent analysis following propensity score matching. Of these, 144 received VBT and 144 received PRT. There was no significant difference in 5-year LRR between VBT and PRT for both intermediate (0% vs. 0%) and high-intermediate risk patients (3.5% VBT vs. 5.4% PRT; HR 0.54: 0.05-6.00; p = 0.616). The subgroup analyses revealed no significant factors favoring PRT over VBT. Patients with high comorbidities may have higher risks of non-cancer death after receiving PRT. Postoperative VBT alone is sufficient for early-stage intermediate-risk endometrial cancer patients.

Tumor location as a risk factor for lymph node metastasis in presumed early-stage endometrioid endometrial cancer patients (1225)

Tumor location as a risk factor for lymph node metastasis in presumed early-stage endometrioid endometrial cancer patients (1225)

Adjuvant radiation therapy in early-stage endometrial cancer with abnormal beta-catenin expression is associated with improved local control

ObjectivesEmerging data suggests that abnormal (nuclear) β-catenin expression in some settings is associated with poorer outcomes. Our study aimed to verify the significance of abnormal β-catenin expression in early-stage endometrial cancer patients and determine if adjuvant radiation therapy (RT) improves local control. MethodsWe identified 213 patients with FIGO 2018 stage I-II endometrioid endometrial cancer who underwent surgery from 2009 to 2021 with β-catenin expression assessed. Vaginal, regional, and distant recurrences were analyzed using competing risk methods, and overall survival was analyzed using Kaplan-Meier. ResultsMedian follow up was 53.2 months; 6.9% experienced vaginal, 8.2% regional, and 7.4% distant recurrence. For the entire cohort, abnormal β-catenin expression was significantly associated with vaginal recurrence and remained significant on multivariate analysis (p = 0.03). There were 114 patients in the no specific molecular profile (NSMP) subgroup, and abnormal β-catenin expression was present in 46.5%. In the NSMP subgroup, abnormal β-catenin expression was associated with increased rates of vaginal recurrence (p = 0.06). Abnormal β-catenin expression in the NSMP subgroup was significant on multivariate analysis for vaginal recurrence (p = 0.04). RT significantly decreased vaginal recurrences in the entire cohort in patients with abnormal β-catenin expression (0%) versus wild type expression (17.5%; p = 0.03). In the NSMP subgroup 0% of patients who received RT versus 20.9% of patients who did not receive RT experienced a vaginal recurrence (p = 0.03). ConclusionUse of adjuvant RT for stage I-II NSMP endometrial cancer with abnormal β-catenin expression improved local control. RT should be considered in these patients to decrease risk of vaginal recurrences.

The impact of lymphovascular space invasion on survival in early stage low-grade endometrioid endometrial cancer

BackgroundThe lymphovascular space invasion (LVSI) is suggested as a prognostic factor for endometrial cancer in many studies, but it has not yet been employed in FIGO staging system. The present study was aimed to evaluate the impact of LVSI on survival in patients with early stage endometrioid endometrial cancer.MethodsThis retrospective cohort was conducted on early stage endometrial cancer patients who underwent surgical staging [total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH/BSO)] and omental biopsy at Referral Teaching Hospitals of Tehran from 2005 to 2021. Patient’s age, menopause status, tumor grade, tumor size, depth of myometrial invasion, LVSI and lower segment involvement were recorded. Data were analyzed with SPSS 22.Results415 patients with stage I and grade 1–2, endometrioid endometrial cancer were analyzed. 100 patients (24.1%) were LVSI-positive. 3-year and 5-year survival rates were 97.1% and 88.9%, respectively. Recurrence occurred in 53 patients (12.8%). 3-year overall survival rates in LVSI-negative and LVSI-positive were 98.7% and 92%. These rates for 5-year survival were 92.1% and 79%, respectively. Recurrence rates in LVSI-negative were 8.9% while it was 25% in LVSI-positive cases. Multivariate analysis showed that LVSI has significant correlation with 3-year and 5-year overall survival rates.ConclusionsLVSI in early stage endometrial cancer significantly and independently influences 3-year and 5-year survival rates and acts as a strong prognostic factor in these patients. LVSI should be implemented in endometrial cancer staging systems due to its significant correlation with cancer recurrence rates and 5-year survival rates.

Serum lipidomic profiling by UHPLC-MS/MS may be able to detect early-stage endometrial cancer.

Nowadays, screening for endometrial cancer (EC) primarily relies on clinical symptoms and imaging, which makes it difficult to detect early-stage disease. Here, we conducted a widely targeted lipidomic analysis of 38 human serum samples in a discovery set and 40 human serum samples in a validation set to profile the dysregulated lipid species and establish lipid biomarkers for early-stage EC. This comprehensive lipidomic determination of 616 serum lipids indicated significant differences between early-stage EC patients and healthy controls. Three phases of lipid biomarker investigation (discovery, validation, and determination of the lipid biomarker panel) were performed, which revealed the upregulation of some sphingolipid, glycerophospholipid, and glycerolipids and downregulation of some carnitine. Consistently, the perturbation of sphingolipid and glycerophospholipid metabolism was also observed from pathway enrichment analysis. Moreover, a lipid biomarker panel, including ursodeoxycholic acid, PC(O-14:0_20:4), and Cer(d18:1/18:0), was established. This panel was assessed as an effective diagnostic model to distinguish early-stage EC patients from healthy controls and atypical endometrial hyperplasia patients within the area under the receiver operating characteristic curve (AUC) reaching 0.903 and 0.928, respectively. In particular, the comparison results of the diagnostic efficacy indicated that the lipid biomarker panel was superior to clinically established indicators for EC diagnosis, including HE4, CA125, CA153, and CA199, suggesting that it could be used as an excellent supplementary method for the diagnosis of early-stage EC. In conclusion, we established a novel and non-invasive lipid biomarker for early-stage EC detection and these findings may provide new insight into the pathological mechanisms of EC.

Lymph-vascular Space Involvement and/or p53 Overexpression Correlated With the Clinical Outcome of Early-stage Endometrial Cancer Patients Treated With Adjuvant Vaginal Brachytherapy.

The majority of patients with endometrial cancer (EC) are diagnosed at an early stage and undergo primary surgery, followed by observation or adjuvant therapy according to risk factors on surgical samples. The objective of this study was to assess the correlation between a risk profile represented by the presence of substantial lymph-vascular space involvement (LVSI) and/or p53 overexpression and the clinical outcome of patients with early-stage endometrial cancer (EC) who received adjuvant vaginal brachytherapy (BT). This investigation assessed 79 patients who underwent hysterectomy, bilateral salpingo-oophorectomy, and pelvic and/o aortic lymphadenectomy or sentinel lymph node biopsy followed by hypofractionated (HDR)-vaginal BT, using 192Ir source, for stage I-II endometrioid (n=70) or non-endometrioid (n=9) EC. Thirty-four patients (43.0%) were considered to have an unfavorable risk profile defined by the presence of substantial LVSI and /or p53 overexpression. Five-year disease-free survival (DFS) and five-year overall survival (OS) were 93.7% and 95%, respectively. There was a significant correlation between unfavorable risk-profile and pelvic recurrence rate (p=0.002) and distant recurrence rate (p=0.017). Patients with abnormal p53 had a higher risk of local relapse (p=0.041). Substantial LVSI was strongly associated with pelvic recurrence (p=0.001) and distant metastasis (p<0.001). The presence of substantial LVSI and/or p53 overexpression strictly correlated with poor outcome of patients with early-stage EC and should be taken into consideration for better planning adjuvant treatment in this clinical setting.

Comprehensive Assessment of ERα, PR, Ki67, P53 to Predict the Risk of Lymph Node Metastasis in Low-Risk Endometrial Cancer

Purpose According to international guidelines, selective lymph node dissection can be performed on patients with early-stage endometrial cancer. However, some patients at early stage have already occurred lymph node metastasis at the time of diagnosis. This study was aimed to find a method to predict the risk of lymph node metastasis in this part of patient. Methods We collected data from 571 patients as training cohort and 351 patients as validation cohort for this study. Then we performed univariate and multivariate analyses to confirm the correlation of frequently used factors and lymph node metastasis. Combined analysis of four commonly indicators (ERα, PR, P53 and Ki67) from pathological parameter sources was mainly carried out, and the combined ratio is defined as (ERα + PR)/(Ki67 + P53). Then the accuracy of the combined ratio and other factors in prediction were compared by AUC value. Also, the optimal truncation value was searched. Finally, patients followed up for more than two years were divided into groups by the threshold value, and their difference in survival was explored. Results This study showed that CA125, grade, LVSI, ERα, PR, P53, Ki67 have statistical significance (P-value <0.05). The AUC value of combined ratio is 0.876, which is the best. The best cutoff value of combined ratio is 1.38 Conclusion The combined ratio cutoff value of 1.38 in this study can be used for prediction of risk of lymph node metastasis in early-stage endometrial cancer patients and provide a reference for therapeutic planning.

Improved Outcomes with Adjuvant Radiation Therapy in Early-Stage Endometrial Cancer with Abnormal Beta-Catenin Expression

<h3>Purpose/Objective(s)</h3> There is increasing data about the prognostic significance of molecular profiling for endometrial cancer outcomes and emerging data showing that abnormal (nuclear) β-catenin expression is associated with an increased risk of recurrence and poorer clinical outcomes. Our study aimed to determine if the addition of adjuvant radiation therapy following surgery improves local control in early-stage endometrial cancer patients with abnormal β-catenin expression. <h3>Materials/Methods</h3> We identified 217 patients with FIGO 2009 stage I and stage II endometrial cancer who underwent surgical resection from 2018 to 2021 at our institution and had molecular data available. We reviewed the β-catenin expression status and outcomes in these patients. Vaginal cuff recurrences, regional recurrences, and distant metastases were analyzed using competing risk methods, and overall survival was analyzed using Kaplan-Meier. <h3>Results</h3> The median follow up time was 22.5 months; 6.9% experienced vaginal, 8.2% regional, and 7.4% distant recurrence. Abnormal β-catenin expression was present in 36.8% of all patients (47% of grade 1-2 versus 17% of grade 3 patients (p=0.007)) and associated with no specific molecular profile subtype. Abnormal β-catenin expression was significantly associated with increased rates of vaginal cuff recurrence (<i>p</i>=0.02), was borderline associated with worse overall survival (<i>p</i>=0.07), and not significantly associated with regional recurrence or distant metastases. One third of patients received adjuvant radiation therapy, generally based on other pathologic factors, and radiation was significantly associated with decreased vaginal cuff recurrences in patients with abnormal β-catenin expression (<i>p</i>=0.01). This decreased incidence of vaginal recurrence was seen with the use of any type of radiation including brachytherapy or external beam radiation therapy. <h3>Conclusion</h3> Patients with Stage I-II endometrial cancer with abnormal β-catenin expression have increased rates of vaginal cuff recurrences, and adjuvant radiation therapy in this group significantly improved local control. Radiation therapy should be considered in patients with endometrial cancers demonstrating abnormal β-catenin expression to decrease the risk of vaginal cuff recurrences.

PO32 Presentation Time: 10:30 AM: Outcomes After Adjuvant Radiation in Patients with Early-Stage Endometrial Cancer with Mismatch Repair Defects

<h3>Purpose</h3> Although mismatch repair (MMR) deficiency is commonly identified in endometrial cancers, its significance on outcomes remains unknown. Our study aims to determine if MMR status affects clinical outcomes in early-stage endometrial cancer patients treated with adjuvant radiation therapy. <h3>Methods/Materials</h3> We identified 194 patients with FIGO 2009 stage I-II endometrioid endometrial cancer who underwent surgical resection followed by adjuvant radiation therapy at our institution with available MMR status. Locoregional recurrence (LRR) and distant metastases were analyzed using competing risk methods, and overall survival (OS) and progression free survival (PFS) were analyzed using Kaplan-Meier. <h3>Results</h3> The median age was 65 years, and the median follow-up time was 38 months. There were 73 patients (37.6%) with an MMR deficiency, and 121 (62.4%) patients with intact MMR. Eleven patients (5.7%) experienced LRR, and 14 patients (7.2%) experienced distant recurrence. The median OS and PFS of the cohort was not reached and MMR status was not associated with OS or PFS. MMR deficiency was significantly associated with the grade of the tumor (17.1% of grade 1 versus 54.4% of grade 2 and 46.9% of grade 3 patients (<i>p</i><0.01)), the depth of myometrial invasion (<i>p</i><0.01), and the presence of LVSI (<i>p</i><0.01). MMR status was not associated with the type of radiation delivered. In the entire cohort, patients who received external beam radiation therapy had significantly worse PFS than patients who underwent brachytherapy (<i>p</i>=0.03). In patients whose tumors were MMR deficient, there was also a significant difference in PFS based on the type of radiation delivered. Patients who underwent external beam radiation therapy (EBRT) had shorter PFS versus patients who underwent brachytherapy only (<i>p</i>=0.02). In patients with MMR deficient tumors, there was a significant correlation between radiation type and stage; patients with stage II disease were more likely to undergo both EBRT and brachytherapy (<i>p</i><0.01). After adjusting for stage, type of radiation delivered was trending towards significance (p=0.07). Greater depth of myometrial invasion was also associated with the use of both EBRT and brachytherapy (<i>p</i>=0.03). <h3>Conclusions</h3> Patients with stage I-II endometrial cancer have excellent oncologic outcomes with the use of adjuvant radiation therapy, regardless of MMR status.