High-risk Endometrial Carcinoma Research Articles

Impact of cachexia on disease recurrence and survival outcomes in endometrial cancer patients

ObjectiveCancer cachexia is progressive weight loss due to muscle/adipose tissue wasting and inadequate intake that occurs in response to malignancy. It is an independent predictor of disease recurrence and reduced survival in several cancers. However, cachexia’s relationship with gynecologic malignancy outcomes has only been examined in small studies with limited follow-up and inconsistent definitions of cachexia. This study investigated the impact of cachexia on disease recurrence and overall survival in high-risk endometrial carcinoma patients. MethodsThis retrospective cohort study examined data from patients with high-risk non-metastatic primary endometrial carcinoma treated at a single institution from 2015 to 2020. Treatment for all subjects included total hysterectomy, surgical staging, pelvic external beam radiotherapy with or without adjuvant chemotherapy. Radiation planning CT datasets were used to measure skeletal musculature at the L3 vertebral level. Skeletal muscle index (SMI) was defined as total L3 skeletal muscle cross sectional area (cm2)/height2 (m2), and cachexia was defined based on SMI. Results55 patients were eligible for analysis. Several SMI thresholds were used to define cachexia, and analysis was performed for each definition. Kaplan-Meier and Cox-proportional hazards regression analysis yielded no significant reduction in overall survival (OS) or progression-free survival (PFS) in patients with cachexia, regardless of threshold chosen. However, 4 of 13 definitions of cachexia showed significantly improved OS in patients without cachexia, relative to those with cachexia. There were no significant differences in disease recurrence. ConclusionsCachexia as defined in this study was not associated with poor outcomes in endometrial carcinoma patients based on OS, PFS, or disease recurrence.

PErsonalized TReatment for Endometrial Carcinoma (PETREC): study design and methods of a prospective Finnish multicenter trial

BackgroundEndometrial carcinomas can be classified into four molecular subgroups – mismatch repair deficient (MMRd), p53 abnormal (p53abn), polymerase-ϵ (POLE) ultramutated, and ‘no specific molecular profile’ (NSMP). Retrospective data imply that...

Serous endometrial intra-epithelial carcinoma: an observational study

BackgroundSerous endometrial intra-epithelial carcinoma is described as a malignant, superficial spreading lesion with risk of extra-uterine spread at time of diagnosis, and poor outcome.ObjectiveTo evaluate the surgical management of patients...

PD-0811 Image-guided Stereotactic Body Radiotherapy for intermediate and high-risk endometrial carcinoma

PD-0811 Image-guided Stereotactic Body Radiotherapy for intermediate and high-risk endometrial carcinoma

24P A phase II trial of docetaxel/cisplatin chemotherapy followed by pelvic radiation therapy in patients with high-risk endometrial carcinoma after staging surgery

The purpose of this study was to evaluate the efficacy of docetaxel/cisplatin chemotherapy followed by pelvic radiation therapy after staging surgery in high-risk endometrial cancer patients. This was a prospective, phase 2, multicenter clinical trial. Eligible patients included surgically staged stage I-II endometrial cancer with high-risk factors and stage III-IV endometrial cancer. Three cycles of chemotherapy consisting of docetaxel (70 mg/m2) and cisplatin (60mg/m2) was started within 5 weeks after staging surgery. Pelvic radiation therapy (45-50.4Gy) was started within 4 weeks after chemotherapy. The primary endpoint was progression-free survival (PFS). A total of 67 patients were enrolled but 9 were excluded. Median age was 54 years (range, 31-73 years). Forty patients (69%) had endometrioid adenocarcinoma. Stage was IIIC in 9 (15%), IVA in 15 (26%), and IVB in 11 patients (19%). Staging surgery was performed by open surgery in 27 patients (46%), laparoscopic surgery in 23 patients (40%), and robotic surgery in 8 patients (14%). Grade 3 and 4 hematologic toxicity was reported in 26 and 43 patients, grade 3 non-hematologic toxicity was reported in 13 patients. After a median follow-up of 58 months (range, 2-101 months), 11 patients had recurrence and 2 of them died of disease. PFS (± SE) was 90% (± 4%), 84.3% (± 4.8 %), 79.9% (± 5.5 %) at 1, 3, and 5 year, respectively. Overall survival (± SE) was 98.3% (± 1.7%), 96.2%, (± 2.6%), 96.2 (± 2.6%) at 1, 3, and 5 year, respectively. Endometrial cancer with high risk factors could benefit from adjuvant chemotherapy using docetaxel/cisplatin followed by radiation therapy with manageable toxicities. Further studies are needed with the incorporation of biological agents to estimate the real benefit of these treatment strategy.

Patterns of Disease Relapses in Patients with High-risk Endometrial Carcinoma Following Concurrent Chemoradiation with Paclitaxel

Patterns of Disease Relapses in Patients with High-risk Endometrial Carcinoma Following Concurrent Chemoradiation with Paclitaxel

MRI- and Histologic-Molecular-Based Radio-Genomics Nomogram for Preoperative Assessment of Risk Classes in Endometrial Cancer

High- and low-risk endometrial carcinoma (EC) differ in whether or not a lymphadenectomy is performed. We aimed to develop MRI-based radio-genomic models able to preoperatively assess lymph-vascular space invasion (LVSI) and discriminate between low- and high-risk EC according to the ESMO-ESGO-ESTRO 2020 guidelines, which include molecular risk classification proposed by "ProMisE". This is a retrospective, multicentric study that included 64 women with EC who underwent 3T-MRI before a hysterectomy. Radiomics features were extracted from T2WI images and apparent diffusion coefficient maps (ADC) after manual segmentation of the gross tumor volume. We constructed a multiple logistic regression approach from the most relevant radiomic features to distinguish between low- and high-risk classes under the ESMO-ESGO-ESTRO 2020 guidelines. A similar approach was taken to assess LVSI. Model diagnostic performance was assessed via ROC curves, accuracy, sensitivity and specificity on training and test sets. The LVSI predictive model used a single feature from ADC as a predictor; the risk class model used two features as predictors from both ADC and T2WI. The low-risk predictive model showed an AUC of 0.74 with an accuracy, sensitivity, and specificity of 0.74, 0.76, 0.94; the LVSI model showed an AUC of 0.59 with an accuracy, sensitivity, and specificity of 0.60, 0.50, 0.61. MRI-based radio-genomic models are useful for preoperative EC risk stratification and may facilitate therapeutic management.

Recurrence and Survival Rates of Patients Who Undergo Minimally Invasive Surgery for Endometrial Carcinoma with Different Prognostic Risk Groups

Objective To compare the recurrence rate and prognosis between minimally invasive surgical (MIS) approach and open surgical approach of endometrial carcinoma (EC) patients with different prognostic risk groups. Methods A retrospective analysis of all cases undergoing EC surgery between January 2011 and March 2018 was performed. The patients were grouped according to the management guidelines of EC patients jointly formulated by the ESGO/ESTRO/ESP 2020. Different surgical approaches were compared with regard to tumor characteristics, recurrence rate, disease-free survival (DFS), and overall survival (OS). Results A total of 665 patients met the inclusion criteria of which 196 patients underwent MIS (29.5%), and 469 patients underwent open surgery (70.5%). In the MIS group, there was a significant higher rate of recurrence (17.3% vs 6.6%, P = 0.000) compared to the open surgery group. The recurrence rate of MIS was 7.7% (P = 0.000) in the medium-high risk group and 8.2% (P = 0.014) in the high-risk group. Multivariate logistic regression analysis showed that the independent factors influencing recurrence included prognostic risk grouping, surgical approach and lymph vascular space invasion (LVSI) positivity (P < 0.05). K-M survival analysis revealed that in the intermediate and high-risk group of EC, MIS patients had a significantly lower DFS than those undergoing open surgery (P < 0.05), but no significant difference was found in OS. Conclusions For patients with EC at moderate and high prognostic risk, MIS is associated with poorer DFS compared to open surgery, but OS was similar across prognostic risk groups. The application of MIS in patients with moderate and high-risk EC needs further research and analysis.

Integrated Biomarker Analysis Reveals L1CAM as a Potential Stratification Marker for No Specific Molecular Profile High-Risk Endometrial Carcinoma.

Histopathologic assessment of high-risk endometrial cancer (EC) suffers from intersubject variability and poor reproducibility. The pragmatic classification in four molecular subgroups helps to overcome these limits, showing a significant prognostic value. The "no specific molecular profile" (NSMP) is the most heterogeneous EC subgroup, requiring further characterization to better guide its clinical management. DNA sequencing of POLE exonuclease domain and immunohistochemistry for PMS2, MSH6, and p53 were performed in order to stratify a cohort of 94 high-risk EC patients in the four molecular subgroups. Moreover, a panel of seven additional biomarkers was tested. Patients were found to be 16% POLE-mutated, 36% mismatch repair-deficient, 27% p53-abnormal, and 21% NSMP. In the multivariable model, molecular groups confirmed their significant association with disease-specific survival and progression-free survival, with p53-abnormal and NSMP endometrial cancer characterized by poor outcomes. Among the additional evaluated biomarkers, L1CAM was the only one with a significant prognostic value within the NSMP subgroup. NSMP/L1CAM-positive patients experienced the worst outcome and were "early-relapsing" after platinum-based chemotherapy, with a significantly shorter platinum-free interval compared to L1CAM-negative patients. L1CAM appears to be a promising candidate as a prognostic and predictive biomarker in the high-risk NSMP subgroup, which is actually known to lack specific molecular markers.

Definitive Radiation Therapy for Medically Inoperable Endometrial Carcinoma

PurposeUpfront radiation therapy consisting of brachytherapy with or without external beam radiation therapy is considered standard of care for patients with endometrial carcinoma who are unable to undergo surgical intervention. This study evaluated the cancer-free survival (CFS), cancer-specific survival (CSS), and overall survival (OS) of patients with endometrial carcinoma managed with definitive-intent radiation therapy. Methods and MaterialsThis was a single-institution retrospective analysis of medically inoperable patients with biopsy-proven endometrial carcinoma managed with up-front, definitive radiation therapy at UMass Memorial Medical Center between May 2010 and October 2021. A total of 55 cases were included for analysis. Patients were stratified as having low-risk endometrial carcinoma (LREC; uterine-confined grade 1-2 endometrioid adenocarcinoma) or high-risk endometrial carcinoma (HREC; stage III/IV and/or grade 3 endometrioid carcinoma, or any stage serous or clear cell carcinoma or carcinosarcoma). The CFS, CSS, OS, and grade ≥3 toxic effects were reported for patients with LREC and HREC. ResultsThe median age was 66 years (range, 42-86 years), and the median follow-up was 44 months (range, 4-135 months). Twelve patients (22%) were diagnosed with HREC. Six patients (11%) were treated with high-dose-rate brachytherapy alone and 49 patients (89%) were treated with high-dose-rate brachytherapy and external beam radiation therapy. Twelve patients (22%) were treated with radiation and chemotherapy. The 2-year CFS was 82% for patients with LREC and 80% for patients with HREC (log rank P = .0654). The 2-year CSS was 100% for both LREC and HREC patients. The 2-year OS was 92% for LREC and 80% for HREC (log P = .0064). There were no acute grade ≥3 toxic effects. There were 3 late grade ≥3 toxic effects owing to endometrial bleeding and gastrointestinal adverse effects. ConclusionsFor medically inoperable patients with endometrial carcinoma, up-front radiation therapy provided excellent CFS, CSS, and OS. The CSS and OS were higher in patients with LREC than in those with HREC. Toxic effects were limited in both cohorts.

Radiotherapy in Medically Inoperable Patients with Endometrial Carcinoma

<h3>Purpose/Objective(s)</h3> Upfront radiotherapy with or without brachytherapy is considered standard of care for patients with endometrial carcinoma that are unable to undergo surgical intervention. Here, we compare the cancer-free (CFS), cancer-specific (CSS), and overall (OS) survival between patients with low-risk and high-risk endometrial carcinoma managed with definitive-intent radiation therapy. <h3>Materials/Methods</h3> This is a single-institutional retrospective analysis of medically-inoperable patients with biopsy-proven endometrial carcinoma managed with upfront, definitive radiotherapy at UMass Memorial Medical Center between May 2010 and October 2021. Fifty-five cases were included for analysis. Patients were stratified as low-risk endometrial carcinoma (LREC: Uterine-confined grade 1/2 endometrioid adenocarcinoma) or high-risk endometrial carcinoma (HREC: Stage III/IV and/or grade 3 endometrioid carcinoma, or any stage serous or clear cell carcinoma or carcinosarcoma). CFS, CSS, OS and grade ≥3 toxicities were reported for patients with LREC and HREC. <h3>Results</h3> Median age was 66 (range: 42-86) with median follow-up being 44 months (range: 4-135). Twelve patients (22%) were diagnosed with HREC. Six patients (11%) were treated with high dose rate (HDR) brachytherapy alone and forty-nine patients (89%) were treated with HDR brachytherapy and external beam radiation therapy (EBRT). Twelve patients (22%) were treated with radiation and chemotherapy. The 2-year CFS was 82% for LREC patients and 80% for HREC patients (log rank p = 0.0654). The 2-year CSS was 100% for both LREC and HREC patients. The 2-year OS was 92% for LREC and 80% for HREC patients (log p = 0.0064). There were no acute grade ≥3 toxicities. There were 3 late grade ≥3 toxicities due to endometrial bleeding and gastrointestinal side effects. <h3>Conclusion</h3> For medically inoperable patients with endometrial carcinoma, upfront radiotherapy provided excellent CFS, CSS and OS. CSS and OS were higher in patients with LREC than those with HREC. Toxicities were limited in both cohorts.

Therapeutic Benefit of Systematic Lymphadenectomy in Node-Negative Uterine-Confined Endometrioid Endometrial Carcinoma: Omission of Adjuvant Therapy

Simple SummaryEndometrial cancer is the most common gynecological tract malignancy in developed countries. Extrauterine disease, in particular lymph node metastasis, is an important prognostic factor. Nevertheless, pelvic lymphadenectomy is not considered to have a therapeutic benefit, as it did not improve survival in randomized studies. However, lymphadenectomy may have a therapeutic benefit if adjuvant therapy can be omitted without decreasing oncological outcomes, as the long-term quality of life is maintained by avoiding morbidities associated with adjuvant therapy. In intermediate- and high-risk endometrioid endometrial carcinomas, adjuvant therapy may be safely omitted without decreasing long-term survival by open surgery including systematic pelvic and para-aortic lymphadenectomy when patients are node-negative. Systematic lymphadenectomy may remove undetectable low-volume lymph node metastasis in both pelvic and para-aortic regions, and open surgery may reduce vaginal recurrence even without vaginal brachytherapy. However, lymphadenectomy may not improve survival in elderly patients and patients with p53-mutant tumors.Endometrial cancer is the most common gynecological tract malignancy in developed countries, and its incidence has been increasing globally with rising obesity rates and longer life expectancy. In endometrial cancer, extrauterine disease, in particular lymph node metastasis, is an important prognostic factor. Nevertheless, pelvic lymphadenectomy is not considered to have a therapeutic benefit, as it did not improve survival in randomized studies. However, lymphadenectomy may have a therapeutic benefit if adjuvant therapy can be omitted without decreasing oncological outcomes, as the long-term quality of life is maintained by avoiding morbidities associated with adjuvant therapy. In intermediate- and high-risk endometrioid endometrial carcinomas, adjuvant therapy may be safely omitted without decreasing long-term survival by open surgery including systematic pelvic and para-aortic lymphadenectomy when patients are node-negative. Systematic lymphadenectomy may remove undetectable low-volume lymph node metastasis in both pelvic and para-aortic regions, and open surgery may reduce vaginal recurrence even without vaginal brachytherapy. However, lymphadenectomy may not improve survival in elderly patients and patients with p53-mutant tumors. In this review, I discuss the characteristics of lymph node metastasis, the methods of lymph node assessment, and the therapeutic benefits of systematic lymphadenectomy in patients with intermediate- and high-risk endometrioid endometrial carcinoma.

557P Tumour mutation burden is a dispensable test in endometrial carcinoma patients whose molecular classification is known

The panel of NCCN Guidelines recommend that Pembrolizumab is useful in patients of recurrent, metastatic, or high-risk endometrial carcinoma with TMB-H or MSI-H at second-line therapy according to the finding of KEYNOTE158, which makes TMB (tumor mutation burden) a key biomarker for the immunotherapy of endometrial carcinoma. TMB is typically calculated from data of whole exome sequencing or targeted sequencing of a panel of a few hundred genes, which means great economic burden for patients. In the initial design of molecular classification, mutation frequency served as one of the important references, thus we explored the proportion of TMB-H patients in subtypes. Publicly available data from publicly available data from the Cancer Genome Atlas (n=507) was analyzed to define the subtypes and calculate the TMB. We also retrospectively analyzed 79 endometrial carcinoma patients (WSB cohort) who performed NGS (733 gene panel) and evaluated for subtypes and TMB. We adopted two methods to define TMB-H and non-TMB-H. In method one, we set cutoff as 10, the same as KEYNOTE158, and the patient with TMB higher than 10 is considered to be a TMB-H patient. According to method one, POLE-mut and MSI-H endometrial carcinoma account for 96.76% (179/185) of TMB-H patients in TCGA cohort and 96.15% (25/26) in WSB cohort. In method two, patients who ranked in the top quartile of TMB were considered as TMB-H. We found that 96.85% (123/127) and 100% (20/20) of TMB-H patients in TCGA and WSB cohort were POLE-mut and MSI-H endometrial carcinoma. In both methods, only one POLE-mut patients (1/49) were non-TMB-H in TCGA cohort and all POLE-mut patients in WSB cohort were TMB-H (3/3). For patients whose molecular classification is known, TMB detection is a dispensable test. Immunotherapy may be admissible for POLE-mut and MSI-H patients without the performance of TMB detection.

Comparison of survival outcomes by adjuvant therapy modality for patients with high-risk endometrial carcinoma (469)

<b>Objectives:</b> There are many approaches to adjuvant therapy for highrisk endometrial carcinoma, including chemotherapy (CT) only, radiation therapy (RT) only, combination "sandwich" therapy (ST: three cycles of CT, followed by RT, then completed with three additional cycles of CT), and other alternative combinations of CT and RT (MT: mixed therapy). The purpose of the study was to compare treatment outcomes for patients with high-risk endometrial carcinoma stratified by the modality of adjuvant therapy. <b>Methods:</b> This single-institution retrospective cohort study evaluated patients with high-risk endometrial carcinoma treated between 2015 and 2019. Following surgical staging, all patients underwent adjuvant therapy. We compared the outcomes of patients treated with ST to patients who received CT only, RT only, or MT. Outcomes included recurrence rate, site of recurrence, progression-free survival, and overall survival. We performed statistical comparisons with Chi-square analysis, Wilcoxon tests, and Fisher's Exact Test. Differences in survival were tested using log-rank tests. <b>Results:</b> Of the 123 evaluable patients, 33 (19.9%) received ST, 58 (33.1%) received CT only, 19 (11.5%) received RT only, and 13 (7.8%) received MT. Demographic, pathologic, and survival outcomes stratified by the modality of adjuvant therapy are described in Table 1. Despite having a more advanced disease (stage IIII/IV, ST: 31/33, 93.0% vs MT: 9/13, 69.2%), patients who received ST had a prolonged progression-free (ST: 20.21 ± 6.60 months vs MT: 8.12 ± 3.55, p=0.0224) and overall (0=0.002) survivals compared to patients who received MT. There were no significant differences in progression-free survival between patients who received ST and those who received CT only or RT only. There were also no significant differences in recurrence rate or site of recurrence between patients who received ST compared to other adjuvant therapy modalities. Patients who received CT only more frequently had stage IVB disease (22/58, 37.9%) than patients who received ST (1/33, 3.0%) and also experienced worse overall survival (p=0.002). There was no difference in overall survival between patients receiving ST compared to RT only. <b>Conclusions:</b> Patients with high-risk endometrial carcinoma treated with ST experienced prolonged progression-free and overall survivals compared to those treated with MT. Additional research is needed to further clarify the role of ST compared to alternative adjuvant treatments for high-risk endometrial carcinoma.

Surgical and oncological outcomes of sentinel lymph node sampling in elderly patients with intermediate to high-risk endometrial carcinoma (547)

<b>Objectives:</b> To evaluate the surgical and oncological outcomes of elderly patients with intermediate to high-risk endometrial cancer (EC) undergoing staging with sentinel lymph node (SLN) sampling and pelvic lymphadenectomy (LND). <b>Methods:</b> A retrospective study was conducted among all elderly (>65-year-old) patients diagnosed with EC between 2007 and 2017 and treated in a single center in Montreal, Canada. We compared the surgical and oncological outcomes of three cohorts undergoing surgical staging in non-overlapping eras: 1) LND, 2) LND and SLN, 3) SLN. Two-year progression-free survival (PFS), overall survival (OS), and disease-specific survival (DSS) were analyzed using life tables, Kaplan-Meier survival curves, and log-rank tests. Odds ratios (OR) and hazard ratios (HR) and their respective 95% confidence intervals (95% CI) were calculated using multivariable logistic regression and Cox proportional hazard models. <b>Results:</b> The study included 278 consecutive patients with a median age of 73 (65-91) years; 84 underwent LND, 120 underwent SLN with LND, and 74 had SLN alone. The SLN group had significantly more grade 2/3 disease (89.2% vs 72.5% and 70.2% in the SLN with LND and the LND groups, respectively, p=0.008) and a trend towards a higher rate of positive nodes (23% vs 14.2% and 14.3% in the SLN with LND and the LND groups, respectively, p=0.22). The SLN group had a shorter total operative time with a median duration of 199 minutes (range: 75-393) compared to 231 (range: 125-403) and 229 (range: 151-440) minutes in the SLN with LND and LND cohorts, respectively (p<0.001), as well as lower, estimated blood loss with a median loss of 20ml (5-150) versus 25ml (5-800) and 40ml (5-400) in the SLN with LND and LND cohorts, respectively (p=0.002). The 2-year OS and PFS were not significantly different between the three groups (p=0.45, p=0.51, respectively). On multivariable analysis after adjusting for age, ASA score, stage, grade, and LVSI, adding SLN was associated with better OS (HR: 0.2, 95% CI: 0.1-0.6, p=0.006), and PFS (HR: 0.5, 95% CI: 0.1-1.0, p=0.05). <b>Conclusions:</b> SLN based surgical staging is feasible and associated with better surgical and oncological outcomes in elderly patients with intermediate and high-risk EC.

A Model to Identify Candidates for Lymph Node Dissection Among Patients With High-Risk Endometrial Endometrioid Carcinoma According to Mayo Criteria.

BackgroundThe Mayo criteria are the most widely accepted algorithm for predicting the risk of lymph node metastasis in endometrial endometrioid carcinoma (EEC). However, the clinical value of these criteria in high-risk patients is limited and inconclusive.MethodsA total of 240 patients with EEC meeting the Mayo high-risk criteria between January 1, 2015, and December 31, 2018 were included in our study. We retrospectively collected the laboratory reports, basic clinical information, clinicopathological and immunohistochemistry (IHC) findings, and the sequences of molecular pathological markers of these patients. A nomogram for predicting the likelihood of positive lymph node status was established based on these parameters.ResultsAmong the 240 patients, 17 were diagnosed with lymph node metastasis. The univariable analyses identified myometrial invasion >50%, aberrant p53 expression, microsatellite instable (MSI), and cancer antigen 125 (CA125) ≥35 U/ml as potential risk factors for lymph node metastasis. The multivariable analyses showed that aberrant p53 expression, MSI, and CA125 ≥35 U/ml were independent predictors of lymph node metastasis. The area under the curve (AUC) for the nomogram was 0.870, as compared to 0.665 for the Mayo criteria.ConclusionsOur novel prediction model effectively identifies patients at high risk for lymphatic metastasis. This model is a promising strategy for personalized surgery in patients with high risk according to the Mayo criteria.

Surgical and oncological outcomes of sentinel lymph node sampling in elderly patients with intermediate to high-risk endometrial carcinoma

ObjectiveWe aimed to evaluate the surgical and oncological outcomes of elderly patients with intermediate to high-risk endometrial cancer undergoing staging with sentinel lymph node (SLN) sampling and pelvic lymphadenectomy.MethodsWe conducted...

Potential competing risk of death in older high-risk endometrial carcinoma patients: Results from a multicentric retrospective cohort

IntroductionAdjuvant therapeutic decisions in older endometrial carcinoma (EC) patients are challenged by a balance between more frequent aggressive EC and comorbidities. We assessed whether EC and comorbidities are competing or cumulative risks in older EC patients. MethodsAll consecutive patients treated for FIGO stage I-IV EC in two University Hospitals in Paris between 2010 and 2017 were retrospectively included. Patients were categorized as: <70 years (y), >70y without comorbidity (fit), and > 70y with a Charlson comorbidity index>3 (comorbid). Association between high-risk EC (2021-ESGO-ETRO-ESP) or comorbidity, and disease-specific-survival (DSS), was evaluated using Cox model (estimation of cause-specific hazard ratio (CSHR), and Fine-Gray model (subdistribution HR) to account for competing events (death unrelated with EC). ResultsOverall, 253 patients were included (median age = 67y, IQR[59–77], median follow-up = 61.5 months, [44.4–76.8]). Among them, 109 (43%) were categorized at high-risk (proportion independent of age), including 67 (26%) who had TP53-mutated tumors. Comorbidity and high-risk group were both associated with all-cause mortality (HR = 4.09, 95%CI[2.29; 7.32] and HR = 3.21, 95%CI [1.69; 6.09], respectively). By multivariate analysis, patients with high-risk EC exhibited poorer DSS, regardless of age/comorbidity (Adjusted-CSHR = 6.62, 95%CI[2.53;17.3]; adjusted-SHR = 6.62 95%CI[2.50;17.5]). Patients>70y-comorbid with high-risk EC had 5-years cumulative incidences of EC-related and EC-unrelated death of 29% and 19%, respectively. In patients <70y, 5-years cumulative incidence of EC-related and EC-unrelated death were 25% and < 1% (one event), respectively. ConclusionHigh-risk EC patients are exposed to poorer DSS regardless of age/comorbidities, comorbidities and cancer being two cumulative rather than competing risks. Our results suggest that age/comorbidity alone should not lead to underestimate EC-specific survival.

Open Surgery including Lymphadenectomy without Adjuvant Therapy for Uterine-Confined Intermediate- and High-Risk Endometrioid Endometrial Carcinoma.

Minimally invasive surgery may not be an appropriate surgical approach in intermediate- and high-risk endometrial carcinoma, even though adjuvant therapy is given. The objective of this study was to evaluate the results of open surgery including lymphadenectomy without adjuvant therapy in patients with uterine-confined intermediate- and high-risk endometrioid endometrial carcinoma. Two hundred fifty-six patients with uterine-confined endometrioid endometrial carcinoma were treated with open surgery, including pelvic with or without para-aortic lymphadenectomy. Of the 81 patients with uterine-confined intermediate- or high-risk disease, 77 were treated with systematic lymphadenectomy without adjuvant therapy. Seven patients developed recurrence, comprising 5.5% (3/55) and 18.2% (4/22) of the intermediate- and high-risk patients, respectively. The time to recurrence was 1–66 months. The sites of recurrence were the vaginal apex (n = 2), lung (n = 2), vaginal sidewall (n = 1), pelvic lymph nodes (n = 1), and para-aortic to supraclavicular nodes (n = 1). Of these, five patients were alive without disease after salvage treatment, but two understaged high-risk patients died of disease. The five-year disease-specific survival rates of intermediate- and high-risk patients were 100% and 90%, respectively. The present study indicated that patients with uterine-confined intermediate- and high-risk endometrioid endometrial carcinoma had excellent survival when treated with open surgery, including lymphadenectomy alone. The safety of omitting adjuvant therapy should be evaluated in prospective randomized trials comparing open surgery with minimally invasive surgery.

L1CAM expression as a predictor of platinum response in high-risk endometrial carcinoma.

For high‐risk endometrial cancer (EC) patients, adjuvant chemotherapy is recommended to improve outcome. Yet, predictive biomarkers for response to platinum‐based chemotherapy (Pt‐aCT) are currently lacking. We tested expression of L1 cell‐adhesion molecule (L1CAM), a well‐recognised marker of poor prognosis in EC, in tumour samples from high‐risk EC patients, to explore its role as a predictive marker of Pt‐aCT response. L1CAM expression was determined using RT‐qPCR and immunohistochemistry in a cohort of high‐risk EC patients treated with Pt‐aCT and validated in a multicentric independent cohort. The association between L1CAM and clinicopathologic features and L1CAM additive value in predicting platinum response were determined. The effect of L1CAM gene silencing on response to carboplatin was functionally tested on primary L1CAM‐expressing cells. Increased L1CAM expression at both genetic and protein level correlated with high‐grade, non‐endometrioid histology and poor response to platinum treatment. A predictive model adding L1CAM to prognostic clinical variables significantly improved platinum response prediction (C‐index 78.1%, P = .012). In multivariate survival analysis, L1CAM expression was significantly associated with poor outcome (HR: 2.03, P = .019), potentially through an indirect effect, mediated by its influence on response to chemotherapy. In vitro, inhibition of L1CAM significantly increased cell sensitivity to carboplatin, supporting a mechanistic link between L1CAM expression and response to platinum in EC cells. In conclusion, we have demonstrated the role of L1CAM in the prediction of response to Pt‐aCT in two independent cohorts of high‐risk EC patients. L1CAM is a promising candidate biomarker to optimise decision making in high‐risk patients who are eligible for Pt‐aCT.