Prognostic factors and survival of endometrial cancer: An 11-year retrospective cohort study in southern Taiwan.

OBJECTIVE: Endometrial cancer (EC) is the most common gynecological malignancy in high-income countries. In Taiwan, the incidence of EC increased from 1.69 in 1980 to 11.36 per 100,000 women/year in 2010. Therefore, we aimed to study the prognostic factors and survival of patients with EC in southern Taiwan. MATERIALS AND METHODS: This study included patients with EC who underwent hysterectomy-based surgery at our hospital between 2010 and 2020. The primary outcome was 5-year progression-free survival (PFS) and overall survival (OS) of patients diagnosed with EC. The secondary outcome was the prognostic factors associated with 5-year PFS and OS in patients with EC. We used the chi-square test to assess categorical variables and the independent t-test to assess continuous variables. The Kaplan-Meier method was used to estimate survival outcomes. Cox regression analysis was conducted to examine the factors associated with PFS and OS. RESULTS: A total of 133 patients were enrolled in this study. The mean age of the patients was 56.5 ± 10.71 years. The mean body mass index was 26.4 ± 5.21 kg/m2. The 5-year PFS and OS were 90.3% and 94.53%, respectively. In terms of PFS, endometrioid histology was linked to more favorable outcomes (hazard ratio [HR] = 0.02, 95% confidence interval [CI]:0.001-0.59), while lymph-vascular space invasion (LVSI) was associated with adverse results (HR = 9.11, 95% CI: 1.07-77.44). Initial analyses revealed no significant correlations between OS and various factors, including age, BMI, parity, DM, hypertension, age at last birth, and tumor grade. However, univariate analysis found grade 3 tumor differentiation, LVSI, and lymph node invasion associated with poorer OS. Laparoscopy was associated with better OS. Nevertheless, subsequent multivariate analysis did not reveal any factor significantly associated with OS. Most patients with EC (76.69%) underwent laparoscopic surgery. CONCLUSION: In conclusion, endometrioid histology was linked to more favorable PFS, while LVSI was related to adverse PFS. Our study did not identify any factors associated with OS. Two-thirds of the patients underwent minimally invasive surgery.

Ovarian Carcinoma: A Single-Centre Eight-Year Case-Series Study with Survival Analysis.

Introduction: This research describes an eight-year case-series of ovarian carcinoma by surgical (pTNM) staging and surgical procedure, explores the characteristics of ovarian surface epithelial cell (OSEC) tumours by histopathological type in a single centre of reference. Material and Methods: survival analysis with overall survivor probabilities for n=263 patients for 12 months and 60-month tumour free survival status (TFS). Results by staging (pTNM stage classification), histotype and for poor surgical candidate (PSC) status are shown. Histotype high grade serous carcinoma (HGSC) was the most frequently diagnosed type (63%). Results: 12-month survivor probabilities according to histotype, rank as follows: clear cell carcinoma (CCC) - 14%; rare carcinoma (RC) - 15%; carcinosarcoma (CS) - 29%; HGSC - 46%; low grade serous carcinoma (LGSC) - 74%; endometrioid carcinoma (EC) - 79%; mucinous carcinoma (MC) - 80% and borderline tumours (BLT) - 94%. At 60 months results are: RC and MC - 0%; CCC - 14%; HGSC - 16%; CS - 29%; LGSC - 62%; EC - 66%; and BLT - 94%. Overall median survival time is 26 months (CI95% 15 to 37); and 20 months when BLT excluded (CI95% CI 15 to 25). Conclusions: These results may guide further research for the OSEC pathology and its histotypes.

Prevalence and size of pelvic sentinel lymph node metastases in endometrial cancer.

AIM OF THE STUDY: To assess the association of prevalence and size of pelvic sentinel node (SLN) metastases with risk factors in endometrial cancer (EC). PATIENTS AND METHODS: Between June 2014 and January 2024 consecutive women with a uterine confined EC undergoing robotic surgery including detection of pelvic SLNs at a University Hospital were included. An anatomically based algorithm utilizing Indocyanine green (ICG) as tracer was adhered to. Ultrastaging and immunohistochemistry (IHC) was applied on all SLNs. The prevalence and size of SLN metastases was assessed with regards to pre- and postoperative histologic types and myometrial invasion estimates. RESULTS: Of 1101 included women 72.6 % (759/1045) had low-grade, 7.6 % (79/1045) high-grade endometroid cancer and 19.8 % (207/1045) non-endometroid cancer. SLN-metastases were present in 174/1045 (16.6 %) women; 9.8 % of preoperatively presumed low-grade endometroid uterine stage 1A (6.4 % of low-grade stage 1A at final histology) and in 58.3 % and 47.8 % respectively in women with high-grade endometroid and non-endometroid uterine stage 1B cancer. In low-grade EC 45/95 (47.4 %) had only isolated tumor cells (ITC) in SLNs compared with 15/78 (19.2 %) in high-grade or non-endometroid cancer (p < .0001) CONCLUSION: This large population-based study, applying a consequent SLN-algorithm over time, provides important detailed information on the risk for, and size of, SLN metastases within risk groups of EC. The 9.8 % risk for metastases in women with presumed low grade uterine stage 1A endometrioid EC motivates detection of SLNs within this subgroup. The proportion of ITCs in SLNs was significantly lower in higher risk histologies.

A rare case of concomitant endometrioid adenocarcinoma arising from uterine adenomyosis and clear cell carcinoma arising from parametrial deep endometriosis.

BACKGROUND: Carcinomatous changes from the ectopic endometrial glands in endometriosis have been reported in many studies, but malignant transformation from uterine adenomyosis/adenomyoma is rare. And clear cell-like adenocarcinoma represents a seldom-encountered malignant pathological variant of ectopic endometrium. CASE PRESENTATION: This case report presents a case of a 44-year-old nulliparous woman begun with abdominal pain and intestinal obstruction. Past medical history showed laparoscopic ovarian endometriotic cyst excision. Ultrasound indicated adenomyoma and a parametrial hypoechoic nodule with abundant blood flow signals and unclear boundaries. Deep invasive endometriosis was considered preoperatively. The patient underwent laparoscopic subtotal hysterectomy and bilateral adnexa resection. Chocolate cyst-like lesion was observed in the parametral lesion. Postoperative pathological examinations suggested endometrioid adenocarcinoma arising from eutopic endometrium and adenomyoma. Ectopic endometrium in the myometrium combined with atypical hyperplasia and formation of endometrioid adenocarcinoma. Left parametrial lesions suggested poorly differentiated endometrioid adenocarcinoma combined with clear cell carcinoma. CD10 + endometrial stromal cells were observed surrounding tumor cell masses. Combined with surgical founding and pathological characters of the left parametrial adenocarcinoma, the parametrial lesions were more likely to be carcinomatous changes of the original deep endometriosis.The patient underwent subsequent transabdominal tumor cell reduction surgery and chemotherapy. CONCLUSION: We herein present a rare case of combined endometrioid adenocarcinoma arising from uterine adenomyosis and clear cell carcinoma arising from parametrial deep endometriosis that may help inspire additional studies in the future. The patient underwent robot-assisted laparoscopic subtotal hysterectomy, bilateral adnexa resection, deep endometriosis lesion resection and bilateral ureteral stent placement. Following surgery, a chemotherapy regimen of Taxol and Carboplatin was administered.

Exploring metastasis and recurrence patterns in low-risk grade 3 endometrial cancer: A multicenter retrospective cohort study.

OBJECTIVE: Females with low-risk endometrial cancer typically have low lymph node metastasis risk and promising prognosis without lymphadenectomy. However, the impact of grade 3 endometrial cancer on nodal involvement, recurrence, and prognosis within this specific subgroup remains unclear. Therefore, in this study, we aimed to investigate the prognosis, patterns of metastasis, and recurrence in a subgroup of females with grade 3 early-stage low-risk endometrioid endometrial cancer. METHODS: We identified patients from the endometrial cancer cohorts of seven institutional hospitals. The study included patients who underwent hysterectomy between January 2013 and December 2021 with preoperative endometrioid histological type, less than half myometrial invasion, no tumor spread outside the corpus on imaging, normal CA-125 level, and histological grade 3. The clinicopathological characteristics and survival outcomes of the patients were collected. Recurrence-free survival was estimated using the Kaplan-Meier method and compared using the log rank test. RESULTS: Overall, 36 patients were included in this analysis. Of the 33 patients who underwent lymphadenectomy, 1 (1/33, 3.0 %) had lymph node metastasis and 27 (75.0 %) received adjuvant therapy. At a median follow-up of 58 months, three females (8 %) had recurrence and all cases involved lymph nodes. The 5-year recurrence-free survival was 88.7 %. No significant difference was observed in the recurrence-free survival between females who did and did not undergo lymphadenectomy (p = 0.554). CONCLUSION: Females diagnosed with low-risk grade 3 endometrial cancer typically have favorable prognosis. However, lymph node metastasis and recurrence risks still exist, with all recorded instances of recurrence involving lymph nodes.

Prognostic significance of lymphovascular space invasion in early-stage low-grade endometrioid endometrial cancer: a fifteen-year retrospective Chinese cohort study.

OBJECTIVE: In 2016, the ESMO-ESGO-ESTRO consensus included LVSI (Lymph-vascular space invasion, LVSI) status as a risk stratification factor for stage I endometrioid endometrial cancer (EEC) patients and as one of the indications for adjuvant therapy. Furthermore, LVSI is included in the new FIGO staging of endometrial cancer (EC) in 2023. However, the data contribution of the Chinese population in this regard is limited. The present study aimed to further comfirm the influence of LVSI on the prognosis of early-stage low-grade EEC in a fifteen-year retrospective Chinese cohort study. METHODS: This retrospective analysis cohort included 702 EEC patients who underwent TAH/BSO surgery, total abdominal hysterectomy, bilateral salpingooophorectomy in Peking University People's Hospital from 2006 to 2020. Patients were stratified based on LVSI expression status as: LVSI negative group and LVSI positive group. Clinical outcome measures related to LVSI, assessed with a univariate and multivariate Cox proportional hazards regression model. RESULTS: 702 EEC patients with stage I and grade 1-2 were analyzed. 58 patients (8.3%) were LVSI-positive and 14 patients (2.0%) was relapse. Recurrence rates in LVSI-negative and LVSI-positive were 1.6% and 6.9%, respectively. 5-year disease-free survival (DFS) rate in LVSI-negative and LVSI-positive were 98.4% and 93.1%, respectively. These rates for 5-year overall (OS) survival in LVSI-negative were 98.9% while it was 94.8% in LVSI-positive. Multivariate analysis showed that LVSI is an independent risk factor for 5-year DFS (HR = 4.60, p = 0.010). LVSI has a similar result for 5-year OS(HR = 4.39, p = 0.028). CONCLUSIONS: LVSI is an independent predictor of relapse and poor prognosis in early-stage low-grade endometrioid endometrial cancer in the Chinese cohort.

The survival benefit associated with complete macroscopic resection in epithelial ovarian cancer is histotype specific.

BACKGROUND: Complete macroscopic resection is a key factor associated with prolonged survival in ovarian cancer. However, most evidence derives from high-grade serous ovarian carcinoma, and the benefit of complete macroscopic resection in other histotypes is poorly characterized. We sought to determine which histotypes derive the greatest benefit from complete macroscopic resection to better inform future decisions on radical cytoreductive efforts. METHODS: We performed multivariable analysis of disease-specific survival across 2 independent patient cohorts to determine the magnitude of benefit associated with complete macroscopic resection within each histotype. RESULTS: Across both cohorts (Scottish: n = 1622; Surveillance, Epidemiology, and End Results [SEER]: n = 18 947), complete macroscopic resection was associated with prolonged disease-specific survival; this was more marked in the Scottish cohort (multivariable hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.37 to 0.52 vs HR = 0.59, 95% CI = 0.57 to 0.62 in SEER). In both cohorts, clear cell ovarian carcinoma was among the histotypes to benefit most from complete macroscopic resection (multivariable HR = 0.23 and HR = 0.50 in Scottish and SEER cohorts, respectively); high-grade serous ovarian carcinoma patients demonstrated highly statistically significant and clinically meaningful survival benefit, but this was of lower magnitude than in clear cell ovarian carcinoma and endometrioid ovarian carcinoma across both cohorts. The benefit derived in low-grade serous ovarian carcinoma is also high (multivariable HR = 0.27 in Scottish cohort). Complete macroscopic resection was associated with prolonged survival in mucinous ovarian carcinoma patients in the SEER cohort (multivariable HR = 0.65), but the association failed to reach statistical significance in the Scottish cohort. CONCLUSIONS: The overall ovarian cancer patient population demonstrates clinically significant survival benefit associated with complete macroscopic resection; however, the magnitude of benefit differs between histotypes.

Prediction of final pathology depending on preoperative myometrial invasion and grade assessment in low-risk endometrial cancer patients: A Korean Gynecologic Oncology Group ancillary study.

OBJECTIVES: Fertility-sparing treatment (FST) might be considered an option for reproductive patients with low-risk endometrial cancer (EC). On the other hand, the matching rates between preoperative assessment and postoperative pathology in low-risk EC patients are not high enough. We aimed to predict the postoperative pathology depending on preoperative myometrial invasion (MI) and grade in low-risk EC patients to help extend the current criteria for FST. METHODS/MATERIALS: This ancillary study (KGOG 2015S) of Korean Gynecologic Oncology Group 2015, a prospective, multicenter study included patients with no MI or MI <1/2 on preoperative MRI and endometrioid adenocarcinoma and grade 1 or 2 on endometrial biopsy. Among the eligible patients, Groups 1-4 were defined with no MI and grade 1, no MI and grade 2, MI <1/2 and grade 1, and MI <1/2 and grade 2, respectively. New prediction models using machine learning were developed. RESULTS: Among 251 eligible patients, Groups 1-4 included 106, 41, 74, and 30 patients, respectively. The new prediction models showed superior prediction values to those from conventional analysis. In the new prediction models, the best NPV, sensitivity, and AUC of preoperative each group to predict postoperative each group were as follows: 87.2%, 71.6%, and 0.732 (Group 1); 97.6%, 78.6%, and 0.656 (Group 2); 71.3%, 78.6% and 0.588 (Group 3); 91.8%, 64.9%, and 0.676% (Group 4). CONCLUSIONS: In low-risk EC patients, the prediction of postoperative pathology was ineffective, but the new prediction models provided a better prediction.

Endometrioid adenocarcinoma arising from abdominal wall endometriosis: A case report and literature review.

Endometriosis, affecting 6%-10% of women of reproductive age, can lead to severe symptoms such as chronic pelvic pain and infertility. Among its rarer manifestations is abdominal wall endometriosis (AWE), which has been increasingly reported following cesarean deliveries. This case discusses a 39-year-old woman who presented with a 13-year history of cyclical pain at her cesarean section scar, exacerbated over the last year by the development of a painful abdominal mass. Medical evaluations indicated endometriosis at the scar, with further investigations including ultrasound and magnetic resonance imaging showing involvement of the rectus abdominis muscle. Elevated tumor markers HE4 and CA-125, along with a biopsy, confirmed adenocarcinoma. The patient underwent extensive surgical treatment, including the resection of the mass, hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy. Pathology confirmed moderately differentiated infiltrative adenocarcinoma originating from endometriosis. Despite the absence of postoperative chemotherapy, the patient showed no recurrence, emphasizing the effectiveness of comprehensive surgical management. This case highlights the critical importance of recognizing the potential for malignant transformation in AWE, particularly following cesarean deliveries, and underscores the necessity for vigilant monitoring and personalized treatment strategies. The management of AWE, especially when malignant transformation is suspected, necessitates a multidisciplinary approach similar to that used in ovarian cancer, focusing on rigorous surgical intervention and the potential for adjuvant therapies.

Endometroid type endometrial cancer after surgery: unravelling the interplay of sleep, fatigue, and psychological well-being.

BACKGROUND: Endometrioid carcinoma, originating in the endometrium glandular cells, is often detected early and treated by surgery. However, post-treatment life quality remains poorly studied, explicitly focusing on sleep quality, fatigue, and depression. METHODS: In this cross-sectional, observational study, 147 female patients with endometrioid-type endometrial carcinoma were evaluated using standardised tools-Pittsburgh Sleep Quality Index (PSQI), Fatigue Assessment Scale (FAS), and Beck Depression Inventory (BDI). Patients were categorised based on sleep quality and depression levels. The study employed correlation and regression analyses to examine the relationships among these variables. RESULTS: No correlations were found between sociodemographic or lifestyle variables and sleep quality, fatigue, or depression (P > 0.05). A strong correlation was identified between PSQI and FAS (r = 0.623; P < 0.001), PSQI and BDI (r = 0.291; P < 0.001), and FAS and BDI (r = 0.413; P < 0.001). Fatigue and tumour grade were potential predictors of poor sleep. Sleep quality and depression predicted fatigue, while only fatigue was a predictor for depression. Radiotherapy and external radiation rates were notably higher in the mild depression group. CONCLUSIONS: Our study suggests an imperative for integrated multi-disciplinary approaches that focus on medical and psychological aspects of patient care to enhance long-term well-being and quality of life.

Integrated histological parameters define prognostically relevant groups in atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia.

OBJECTIVE: To assess the risk of endometrial carcinoma following a diagnosis of atypical hyperplasia/endometrioid intraepithelial neoplasia by endometrial biopsy, stratified based on integrated histological parameters. METHODS: All women with atypical hyperplasia/endometrioid intraepithelial neoplasia undergoing hysterectomy within 1 year of diagnosis without progestin treatment were included. Patients were subdivided into three study groups, based on two criteria: (a) grade of nuclear atypia and (b) foci (<2 mm) of confluent glands with no intervening stroma: low-grade, high-grade, and confluent glands. The rate of endometrial carcinoma on the subsequent hysterectomy was assessed in each study group, and differences between study groups were assessed using Fisher's exact test, with a significant p value <0.05. Reproducibility was assessed by using Cohen's κ. RESULTS: Ninety-six patients were included. Overall, 36 of 96 patients (37.5%) had endometrial carcinoma on the subsequent hysterectomy. The number of endometrial carcinomas was 4 of 42 (9.5%) in the low-grade group, 14 of 28 (50.0%) in the high-grade group, and 18 of 26 (69.2%) in the confluent glands group. The rate of endometrial carcinoma was significantly higher in the high-grade group than in the low-grade group (p<0.001), whereas it did not significantly differ between the high-grade group and the confluent glands group (p=0.176). The reproducibility among pathologists was moderate for low-grade versus high-grade (κ=0.58) and substantial for confluent glands versus low-grade (κ=0.63) and high-grade (κ=0.63). CONCLUSION: Atypical hyperplasia/endometrioid intraepithelial neoplasia can be stratified into prognostically relevant groups based on integrated histological parameters, with a possible major impact on patient management.

Synchronous Well-Differentiated Papillary Mesothelioma and Endometrioid Adenocarcinoma Arising From Endometriosis.

Well-differentiated papillary mesothelioma (WDPM) is a rare mesothelial tumor of uncertain malignant potential. We present a unique case of a woman with synchronous WDPM and well-differentiated endometrioid adenocarcinoma (EA) arising from extraovarian endometriosis. A 56-year-old postmenopausal woman presented with a several-month history of right lower quadrant abdominal pain. She had a history of supracervical hysterectomy and bilateral salpingo-oophorectomy secondary to endometriosis. Imaging reported a mass in the right lower quadrant originating from the distal ileum. At laparotomy, the patient underwent a right colectomy with resection of the terminal ileum and excision of a solitary peritoneal nodule. Pathology was consistent with a diagnosis of well-differentiated EA (arising from extraovarian endometriosis) and WDPM. Further treatment consisted of complete surgical staging/debulking and adjuvant chemotherapy directed toward metastatic well-differentiated EA. Surgeons should be familiar with WDPM as a potential finding in women of reproductive age undergoing abdominal surgery for any indication.

How deep is too deep? Assessing myometrial invasion as a predictor of distant recurrence in stage I endometrioid endometrial cancer.

OBJECTIVES: The goal of this study was to evaluate the depth of myometrial invasion as a predictor of distant recurrence in patients with node-negative stage IB endometrioid endometrial cancer. METHODS: A retrospective multicenter study, including surgically staged endometrial cancer patients at Mayo Clinic, Rochester (MN, USA) between January 1999 and December 2017, and Fondazione Policlinico Universitario A. Gemelli (Rome, Italy) between March 2002 and March 2017, was conducted. Patients without lymph node assessment were excluded. The follow-up was restricted to the first 5 years following surgery. Recurrence-free survival was estimated using the Kaplan-Meier method. Cox proportional hazards models were fit to evaluate the association of clinical and pathologic characteristics with the risk of recurrence. RESULTS: Of 386 patients, the mean (SD) depth of myometrial invasion was 70.4 (13.2)%. We identified 51 recurrences (14 isolated vaginal, 37 non-vaginal); the median follow-up of the remaining patients was 4.5 (IQR 2.3-7.0) years. At univariate analysis, the risk of non-vaginal recurrence increased by 64% (95% CI 1.28 to 2.12) for every 10-unit increase in the depth of myometrial invasion. International Federation of Gynecology and Obstetrics (FIGO) grade and myometrial invasion were independent predictors of non-vaginal recurrence. The 5-year non-vaginal recurrence-free survival was 95.2% (95% CI 92.0% to 98.6%), 84.0% (95% CI 76.6% to 92.1%), and 67.1% (95% CI 54.2% to 83.0%) for subsets of patients with myometrial invasion <71% (n=207), myometrial invasion ≥71% and grade 1-2 (n=132), and myometrial invasion ≥71% and grade 3 (n=47), respectively. A total of 256 (66.3%) patients received either vaginal brachytherapy only or no adjuvant therapy. Patients who received adjuvant chemotherapy, regardless of receipt of external beam radiotherapy or vaginal brachytherapy, had an approximately 70% lower risk of any recurrence (HR adjusted for age, grade, myometrial invasion 0.31, 95% CI 0.12 to 0.85) and of non-vaginal recurrence (adjusted HR 0.32, 95% CI 0.10 to 0.99). CONCLUSION: The invasion of the outer third of the myometrium and histologic grade were found to be independent predictors of distant recurrence among patients with endometrioid, node-negative stage IB endometrial cancer. Future studies should investigate if systemic adjuvant therapy for patients with myometrial invasion of the outer third would improve outcomes.

Tailoring postoperative management through sentinel lymph node biopsy in low- and intermediate-risk endometrial cancer - the SENTRY clinical trial.

BACKGROUND: While total hysterectomy and bilateral salpingo-oophorectomy without lymph node staging are standard for low- and intermediate-risk endometrial cancer, certain histopathologic factors revealed after surgery can necessitate additional interventions. Our study assessed the influence of sentinel lymph node biopsy on postoperative decision-making. MATERIALS AND METHODS: In the SENTRY trial (July 2021 - February 2023), we enrolled patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IA-IB low-grade endometrioid endometrial cancer. Laparoscopic sentinel lymph node mapping using indocyanine green was performed alongside total hysterectomy with bilateral salpingo-oophorectomy. Subsequent management changes based on sentinel lymph node biopsy results were evaluated. The trial was registered at ClinicalTrials.gov (NCT04972682). RESULTS: Of the 100 enrolled participants, a bilateral detection rate of 91% was observed with a median detection time of 10 min (interquartile range 8-13 min). Sentinel lymph node metastases were found in 8% (N = 8) of participants. Postoperative FIGO staging increased in 15% (N = 15) and decreased in 5% (N = 5) of patients. Sentinel lymph node biopsy results altered the adjuvant treatment plan for 20% (N = 20): external beam radiotherapy was omitted in 12% (N = 12) while 6% (N = 6) had external beam radiotherapy +/- systemic chemotherapy added due to sentinel lymph node metastases. In 2% (N = 2), the external beam radiotherapy field was expanded with the paraaortic region. No intraoperative complications were reported and no 30-day major morbidity and mortality occurred. Throughout a median follow-up of 14 (95% CI 12-15 months, neither patient-reported lymphedema nor pelvic recurrence surfaced in the cohort. CONCLUSIONS: Sentinel lymph node biopsy using indocyanine green is a safe procedure and allows tailoring adjuvant therapy in presumed low- and intermediate-risk endometrial cancer. It assists in avoiding external beam radiotherapy overtreatment and introducing additional modalities when necessary.

Is it safe to operate selected low-risk endometrial cancer patients in secondary hospitals?

INTRODUCTION: The aim of this study was to assess the accuracy of a preoperative screening algorithm in identifying low-risk endometrial cancer (EC) patients to ensure optimal care. METHODS: A total of 277 patients with primary EC confirmed through biopsy underwent magnetic resonance imaging (MRI). Patients with risk factors for advanced high-risk EC, such as non-endometrioid histology, high-grade differentiation status, deep myometrial invasion, or spread beyond the uterine corpus, were systematically excluded. The remaining preoperatively screened patients with stage IA low-grade endometrioid EC (EEC) (n = 93) underwent surgery in a tertiary hospital. The accuracy of the preoperative diagnosis was evaluated by comparing the findings with the postoperative histopathological results. Disease-free survival (DFS) and overall survival (OS) were analyzed using 8-year follow-up data. RESULTS: Postoperative histopathological analysis revealed that all patients had grade 1-2 EEC localized to the corpus uteri. Only three patients had deep myometrial invasion (stage IB), but they remained disease-free after 6-9 years of follow-up. The median follow-up time for all patients was 8.7 years. The DFS was 7.6 years, and the OS was 8.6 years. Two patients with stage IA grade 1 EEC experienced relapse and, despite treatment, died of EC. No other EC-related deaths occurred. CONCLUSIONS: The screening algorithm accurately identified low-risk EC patients without compromising survival. Therefore, the algorithm appears to be feasible for selecting patients for surgery in secondary hospitals.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. CLINICAL TRIAL REGISTRATION: NCT05793333.

Alpha-fetoprotein producing endometrioid carcinoma arising in an adenomyoma of the uterus.

We report a case of alpha-fetoprotein-producing endometrioid carcinoma (AFP-EC) that originated within an adenomyoma of the uterine corpus. A 76-year-old Japanese woman was incidentally discovered to have a uterine tumor along with multiple lung nodules. Upon surgical removal of the uterus, it was revealed that the tumor was situated within the adenomyoma. The tumor exhibited microfollicular structures and solid growth patterns, with hyaline globules, clear cell glands, and primitive tumor cells. Immunohistochemical analysis indicated the presence of germ cell markers, including AFP, SALL4, and glypican3, leading to final diagnosis of AFP-EC. Histopathologically, AFP-ECs exhibit characteristics similar to those of AFP-producing neoplasms in other organs. Furthermore, a nomenclature issue arises when distinguishing AFP-ECs from yolk sac tumors of the endometrium in older patients due to their shared features. The concept of retrodifferentiation or neometaplasia suggests that "endometrioid carcinoma with yolk sac tumor differentiation" or "endometrioid carcinoma with a primitive phenotype" may serve as more fitting terms for the diverse spectrum of AFP-producing neoplasms in the endometrium. In conclusion, this case underscores the diagnostic challenges posed by AFP-ECs arising from adenomyomas and emphasizes the need for refining the nomenclature and classification of AFP-producing neoplasms within the endometrium.

Molecular and pathologic data to guide selection of patients with endometrioid endometrial cancer for ovarian preservation.

OBJECTIVES: To investigate the association of molecular and pathologic factors with concurrent or recurrent ovarian disease to guide ovarian preservation in endometrioid endometrial cancer. METHODS: Patients with endometrial cancer ≤50 years of age at diagnosis were grouped by elective oophorectomy versus ovarian preservation at staging (January 2010 to June 2021). Tumors were stratified by molecular sub-type and CTNNB1 mutational status with next generation sequencing and immunohistochemistry. Germline data identified patients with Lynch syndrome. Associations between molecular/pathologic features and concurrent ovarian disease in patients electing oophorectomy were compared with the Wilcoxon rank-sum and Fisher's exact tests. Associations with isolated ovarian recurrences in patients who chose ovarian preservation were examined using survival analyses. RESULTS: Among 317 patients with endometrial cancer who underwent bilateral oophorectomy, 27 (9%) had malignant ovarian tumors, of whom 11 (41%) had no gross ovarian involvement on intra-operative survey. For patients with sequencing, concurrent malignant ovarian tumors were diagnosed in 0/14 (0%) POLE, 2/48 (4%) copy number-low/no specific molecular profile, 10/22 (45%) microsatellite instability-high, and 3/6 (50%) copy number-high/TP53abnormal patients (p<0.001). Concurrent malignant ovarian tumors were present in 1/30 (3%) hotspot CTNNB1-mutated versus 10/60 (17%) wildtype/CTNNB1 non-hotspot mutated endometrial cancer patients (p=0.11) and 7/28 (25%) Lynch versus 7/74 (9%) non-Lynch syndrome patients (p=0.06). Concurrent malignant ovarian tumors were present in patients with higher grade endometrial cancer (5% grade 1 vs 20% grade 2 and 24% grade 3; p<0.001), present versus absent lymphovascular space invasion (20% vs 6%; p=0.004), positive versus negative pelvic washings (28% vs 7%; p=0.016), and ≥50% versus <50% myoinvasion (24% vs 7%; p=0.004). Of 103 patients who chose ovarian preservation, four had isolated ovarian recurrences (two had high-risk pathologic features and two had high-risk molecular features). CONCLUSIONS: The integration of molecular and pathologic data may improve risk stratification of pre-menopausal patients with endometrial cancer and enhance candidate selection for ovarian preservation.

The analysis of preoperative or intraoperative factors in predicting the escalation of surgical pathological staging of patients with clinical stage I endometrioid carcinoma: A retrospective clinical study.

To retrospectively analyze the preoperative and intraoperative influencing factors in predicting the escalation of surgical pathological staging in patients with clinical stage I endometrioid carcinoma. Patients with clinical stage I endometrioid carcinoma at Women's Hospital, School of Medicine, Zhejiang University, between January 2002 and December 2015 were enrolled in this study. Due to preoperative or intraoperative surgical exploration, the patients with one or more preoperative or intraoperative high-risk factors underwent total hysterectomy, bilateral salpingo-oophorectomy and lymphadenectomy, totaling 535 cases. The preoperative and intraoperative influencing factors that could lead to the escalation of postoperative surgical pathological staging were further analyzed. 1. There were 535 patients diagnosed with clinical stage I endometrioid carcinoma before surgery, 125 patients were upgraded with postoperative pathological staging, for a rate of 23.36%. 2. Kaplan-Meier survival curve analysis showed that the prognosis in postoperative surgical pathological staging upgraded cases was worse than that in nonupgraded cases. The tumor-free survival and overall survival rates in the 2 groups were significantly different (P < .001). 3. Univariate analysis showed that preoperative degree of myometrial infiltration, intraoperative visual myometrial infiltration depth, massive size of tumor (diameter ≥ 4 cm) and preoperative abnormal serum cancer antigen 125 (CA125) level were associated with the escalation of surgical pathological staging (P < .05). Multivariate analysis indicated that massive size of tumor and preoperative serum abnormal CA125 level were independent predictors of whether postoperative pathological staging would be upgraded (P < .05). 4. The receiver operating characteristic curve drawn with the massive size of tumor and/or the preoperative serum CA125 level abnormality could be used to predict the probability of postoperative pathological upstaging. The results showed that the area from the combination of the 2 factors under the receiver operating characteristic curve was 0.723 (95% confidence interval, 0.672-0.773), suggesting that the combination of massive size of tumor and abnormal preoperative serum CA125 level may serve as an influencing factor for predicting the postoperative pathological staging upgrades. The clinical stage I endometrioid carcinoma patients with massive size of tumor and abnormal preoperative serum CA125 level need to be fully evaluated to ensure appropriate management as soon as possible, since they are more likely to experience postoperative pathological staging upgrades.

Prognostic evaluation of lymph-vascular space invasion in patients with endometrioid and non-endometrioid endometrial cancer: A multicenter study.

INTRODUCTION: The prognostic value of lymph-vascular space invasion (LVSI) on endometrial cancer (EC) remains controversial. This study aimed to explore the impact of LVSI on patients with endometrioid and non-endometrioid EC in China. MATERIALS AND METHODS: We analyzed EC patients who underwent surgery from 2010 to 2019 in seven Chinese hospitals retrospectively and stratified patients based on histopathologic types and LVSI status. Endpoints were disease-free survival (DFS) and overall survival (OS). Propensity score matching (PSM) algorithm was used to balance the confounding factors. The survival was examined using Kaplan-Meier analysis. Cox proportional hazards regression analyses were used to find prognostic independent risk factors. RESULTS: Among 3715 EC patients, LVSI positive rate was 9.31% (346/3715). After matching, LVSI present group had shorter DFS (P = 0.005), and similar OS (P = 0.656) than LVSI absent group for endometrioid EC patients. For non-endometrioid EC patients, there was no statistical difference in either DFS (P = 0.536) or OS (P = 0.512) after matching. The multivariate Cox analysis showed that LVSI was an independent risk factor of DFS [hazard ratio (HR) 2.62, 95% confidence intervals (CI) 1.35-5.10, P = 0.005] and not OS (HR 1.24, 95%CI 0.49-3.13, P = 0.656) for endometrioid EC patients. It was not a prognostic factor of either DFS (HR 1.28, 95%CI 0.58-2.81, P = 0.539) or OS (HR 1.33, 95%CI 0.55-3.13, P = 0.515) for non-endometrioid EC patients. CONCLUSION: LVSI is an adverse prognostic factor for endometrioid EC patients and has no impact on non-endometrioid EC patients. Necessity of postoperative adjuvant therapy based on LVSI needs to be carefully considered for non-endometrioid EC patients.