Non-endometrioid Histology Research Articles

Real-world perioperative treatment patterns and burden of recurrent disease in patients with high-risk endometrial cancer: a SEER-Medicare study

Objectives To elucidate unmet needs in high-risk endometrial cancer (EC), this study described perioperative treatment patterns in Medicare beneficiaries with high-risk EC and quantified the impact of disease recurrence on clinical and economic outcomes among patients receiving adjuvant therapy. Methods Patients aged ≥66 years with high-risk EC (stage I/II EC of non-endometrioid histology or stage III/IVA EC of any histology) receiving hysterectomy with bilateral salpingo-oophorectomy from SEER-Medicare data (2007–2019) were identified; perioperative treatment patterns were described. Post-operative treatment patterns were described among patients receiving adjuvant therapy; overall survival (OS), all-cause and EC-related healthcare resource utilization and costs were evaluated from recurrence date (using a claims-based algorithm developed with clinical input) for recurrent patients and from a frequency-matched date for non-recurrent patients. Results Of 2,279 patients receiving EC surgery, 3.1% received neoadjuvant therapy and 55.3% received adjuvant therapy. Among 1,199 patients receiving adjuvant therapy, systemic adjuvant therapy with radiation (38.9%) was most common. Median OS was 1.4 years among 378 (31.5%) recurrent patients identified over a median follow-up of 3.7 years. Recurrent patients had significantly higher per-patient-year rates of all-cause outpatient visits (37.7 vs. 22.6), EC-related outpatient visits (14.5 vs. 3.0), and all-cause hospitalizations (1.3 vs. 0.4) than non-recurrent patients, and an excess of $84,562 and $62,128 in all-cause and EC-related annual costs, predominantly driven by hospitalizations. Conclusions Our findings highlight the considerable clinical and economic burden experienced by patients with high-risk EC experiencing recurrence and emphasize the unmet need for novel therapies in early settings to mitigate this burden.

Association of glutaminase expression with immune-suppressive tumor microenvironment, clinicopathologic features, and clinical outcomes in endometrial cancer

ObjectiveIncreased glutamine metabolism by cancer cells via upregulation of the drug-targetable enzyme glutaminase may contribute to an immune-suppressive tumor microenvironment. Inhibiting glutamine metabolism can not only suppress tumor growth, but...

Performance of transvaginal ultrasound in evaluation of endometrioid versus non-endometrioid cancers.

401 Background: Measurement of endometrial thickness by transvaginal ultrasound (TVUS) is the standard of care for evaluation of patients with postmenopausal bleeding, the most common presenting symptom of endometrial cancer. However, the sensitivity of TVUS has not been clearly established in the setting of non-endometrioid histology, which is more aggressive and does not arise from endometrial hyperplasia. This study aims to evaluate the endometrial stripe (EMS) detection rate and sensitivity of TVUS in non-endometrioid compared to endometrioid endometrial cancers. Methods: In this retrospective cohort study, we included endometrial cancer cases diagnosed at a single institution from 01/01/2019 to 04/01/2024 who were enrolled in the Discovery and Evaluation of Testing for Endometrial Cancer in Tampons (DETECT) study who had TVUS during their initial clinical evaluation. Demographic characteristics and results from TVUS reports were obtained from the electronic medical record. Endometrial stripe thickness of less than 5mm is considered a negative result, whereas endometrial thickness of 5mm or greater (5mm+) is considered positive. The primary outcomes were the ability to measure EMS and the sensitivity of TVUS at a cutoff of 5mm+ for endometrial cancer detection, overall and by race and histology. We assessed differences using chi-squared tests. Results: Of the 349 patients included in our analysis, 247 (71%) had endometrioid histology, and 102 (21%) had non-endometrioid histology. There were 98 (28%) Black patients (49% non-endometrioid) and 242 (69%) White patients (22% non-endometrioid). The EMS was adequately measured in 98% of patients with endometrioid histology compared to 91% of patients with non-endometrioid histology (p=0.001). When stratified by race, EMS was visualized in 100% of Black patients with endometrioid histology but 89% of Black patients with non-endometrioid histology (p=0.02). This difference was seen but not significant in White patients with 98% measurable endometrial stripes in endometrioid cancer and 92% in non-endometrioid cancer (p=0.05). The ability to measure EMS was not different when compared by race alone. The sensitivity of TVUS (EMS of 5mm+) was higher in patients with endometrioid histology (99%) than patients with non-endometrioid histology (94%; p=0.03). Conclusions: In one of the largest and most diverse studies of TVUS performance in endometrial cancer patients to date, TVUS was more effective at visualizing the EMS and had higher sensitivity in patients with endometrioid compared to non-endometrioid endometrial cancers. While performance did not vary by race, the prevalence of non-endometrioid cancers was twice as high among Black compared to White patients. Our findings suggest that TVUS may be less accurate for diagnosing non-endometrioid endometrial cancer, which disproportionately affects Black women.

Racial discrepancies in initial presentation and diagnosis of patients with endometrial cancer.

89 Background: Endometrial cancer incidence and mortality are increasing, particularly in Black patients who have more aggressive non-endometrioid subtypes. Racial disparities in mortality may be partially contributable to early clinical factors including recognition of symptoms, type of evaluation, and referral timing. We evaluated differences in factors related to symptom appraisal and delays in diagnosis by race and histology. Methods: In this retrospective cohort study, we included patients diagnosed with endometrial cancer from 01/01/2019 to 09/01/2023 at a single institution who were enrolled in the Discovery and Evaluation of Testing for Endometrial Cancer in Tampons (DETECT) study. Demographic characteristics and factors regarding initial presentation and workup were obtained from the electronic medical record. We evaluated patient-reported length and type of symptoms at initial presentation, diagnostic imaging type, and time from initial presentation to time of imaging, tissue sampling, and referral to gynecologic oncology. We assessed differences by race and histology (endometrioid vs. non-endometroid) using chi-square and Kruskal-Wallis tests and analysis of variance. Results: Of the 335 patients included in our analysis, 237 (70.7%) had endometrioid and 98 (29.3%) had non-endometrioid histology. Patients with endometrioid histology were significantly more likely to be younger, White, non-smokers, and have higher obesity levels by body mass index than those with non-endometrioid histology (p=<0.01). The length of symptoms at time of initial presentation was significantly longer in Black patients overall (p=0.01) and in Black patients with endometrioid histology compared to their White counterparts (p=0.04). A similar trend was seen in patients with non-endometrioid histology but was not statistically significant (p=0.15). There was no difference in type of symptoms reported. The type of imaging (p=0.005) differed significantly between endometrioid and non-endometrioid groups. White patients were more likely to have a transvaginal ultrasound performed at initial presentation (p=0.004). Black patients with endometrioid endometrial cancer were more likely to have a longer time period from initial presentation to referral to gynecologic oncology (p=0.04) despite having a shorter time between initial presentation and endometrial sampling (p=0.04). Conclusions: In our cohort, Black patients with endometrial cancer were more likely to have experienced symptoms for a longer time period prior to presentation, less likely to be evaluated with transvaginal ultrasound, and had a longer time period between initial presentation and referral to gynecologic oncology compared to White patients. Raising awareness and targeting these early steps in evaluation and detection of endometrial cancer may help decrease racial disparities in outcomes.

2009 International Federation of Gynecology and Obstetrics (FIGO) stage IIIA endometrial cancer: oncologic outcomes based on involvement of adnexa, serosa, or both

ObjectiveTo assess clinicopathologic features and survival outcomes of patients with endometrial carcinoma involving adnexal, full-thickness serosal, or combined involvement.MethodsThis international, multi-institutional, retrospective study examined patients with 2009 International Federation of...

ENGOT-en11/GOG-3053/KEYNOTE-B21: a randomised, double-blind, phase III study of pembrolizumab or placebo plus adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed, high-risk endometrial cancer

Pembrolizumab plus chemotherapy provides clinically meaningful benefit as first-line therapy for advanced (locoregional extension and residual disease after surgery)/metastatic/recurrent mismatch repair-proficient (pMMR) and mismatch repair-deficient (dMMR) endometrial cancer, with greater magnitude of benefit in the dMMR phenotype. We evaluated the addition of pembrolizumab to adjuvant chemotherapy (with/without radiation therapy) among patients with newly diagnosed, high-risk endometrial cancer without any residual macroscopic disease following curative-intent surgery. We included patients with histologically confirmed high-risk [International Federation of Gynecology and Obstetrics (FIGO) stage I/II of non-endometrioid histology or endometrioid histology with p53/TP53 abnormality, or stage III/IVA of any histology] endometrial cancer following surgery with curative intent and no evidence of disease postoperatively, with no prior radiotherapy or systemic therapy. Patients were randomised to pembrolizumab 200 mg or placebo every 3 weeks (Q3W) for six cycles added to carboplatin-paclitaxel followed by pembrolizumab 400 mg or placebo every 6 weeks (Q6W) for six cycles per treatment assignment. Radiotherapy was at the investigator's discretion. The primary endpoints were investigator-assessed disease-free survival (DFS) and overall survival in the intention-to-treat population. A total of 1095 patients were randomised (pembrolizumab, n= 545; placebo, n= 550). At this interim analysis (data cut-off, 4 March 2024), 119 (22%) DFS events occurred in the pembrolizumab group and 121 (22%) occurred in the placebo group [hazard ratio 1.02, 95% confidence interval (CI) 0.79-1.32; P= 0.570]. Kaplan-Meier estimates of 2-year DFS rates were 75% and 76% in the pembrolizumab and placebo groups, respectively. The hazard ratio for DFS was 0.31 (95% CI 0.14-0.69) in the dMMR population (n= 281) and 1.20 (95% CI 0.91-1.57) in the pMMR population (n= 814). Grade ≥3 adverse events (AEs) occurred in 386 of 543 (71%) and 348 of 549 (63%) patients in the pembrolizumab and placebo groups, respectively. No treatment-related grade 5 AEs occurred. Adjuvant pembrolizumab plus chemotherapy did not improve DFS in patients with newly diagnosed, high-risk, all-comer endometrial cancer. Preplanned subgroup analyses for stratification factors suggest that pembrolizumab plus chemotherapy improved DFS in patients with dMMR tumours. Safety was manageable. ClinicalTrials.gov, NCT04634877; EudraCT, 2020-003424-17. Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Biomolecular Classification in Endometrial Cancer: Onset, Evolution, and Further Perspectives: A Critical Review.

Since the new guidelines for endometrial cancer risk classification have been published, many reviews have proposed a critical re-evaluation. In this review, we look back to how the molecular classification system was built and its evolution in time to highlight the major flaws, particularly the biases stemming from the inherent limitations of the cohorts involved in the discoveries. A significant drawback in some cohorts is the inclusion criteria, as well as the retrospective nature and the notably sparse numbers, especially in the POLEmut (nonsynonymous mutation in EDM domain of POLE) risk groups, all of which impact the reliability of outcomes. Additionally, a disregard for variations in follow-up duration leads to a non-negligible bias, which raises a substantial concern in data interpretation and guideline applicability. Finally, according to the results that we obtained through a re-analysis of the confirmation cohort, the p53abn (IHC positive for p53 protein) subgroup, which is predominant in non-endometrioid histology (73-80%), loses its predictivity power in the endometrioid cohort of patients. The exclusion of non-endometrioid subtypes from the cohort led to a complete overlap of three molecular subgroups (all except POLEmut) for both overall and progression-free survival outcomes, suggesting the need for a more histotype-specific approach. In conclusion, this review challenges the current ESGO/ESTRO/ESP guidelines on endometrial cancer risk classification and highlights the limitations that must be addressed to better guide the clinical decision-making process.

Treatment of endometrial cancer from 2000 to 2020 in Germany: a retrospective population based cohort study

PurposeEndometrial cancer (EC) is one of the most common malignancies among women in western countries. This study aimed to assess data on patient treatment in Germany throughout two decades to evaluate the development and effect of surgery, radiation, and chemotherapy.MethodsThis retrospective registry study included 34,349 EC patients diagnosed between 2000 and 2020. Patients were classified into five risk groups. Overall survival was analyzed by Kaplan–Meier method as well as univariable and multivariable Cox regression to evaluate risk factors and treatment options.ResultsOver the study period, minimal invasive surgery was used more often compared to open surgery and was associated with better overall survival. Patients with advanced EC were more likely to receive multimodal therapy.Patients with intermediate risk EC had a good prognosis upon surgery, which further improved when radiotherapy was added. High-risk patients showed poorer prognosis but clearly benefited from additional radiotherapy. Survival of elderly high-risk patients with a non-endometrioid histology was improved when chemotherapy was added to surgery and radiotherapy.ConclusionOur study includes a large analysis of data from German clinical cancer registries on the care of endometrial cancer during two decades. We observed an increase of minimal invasive surgery. There is evidence that minimal invasive surgery is not inferior to open surgery. Adjuvant radio- and chemotherapy further improves survival depending on risk group and age.

Endometrial cancer with positive sentinel lymph nodes: pathologic characteristics of metastases as predictors of extent of lymphatic dissemination and prognosis

ObjectivesTo assess predictors of extensive lymph node dissemination and non-vaginal recurrence in patients with endometrial cancer with positive sentinel lymph nodes (SLNs).MethodsPatients with endometrial cancer who underwent primary surgery with...

Nodal staging in high and high-intermediate risk endometrial cancer surgery: Which role in the molecular classification era?

ObjectivesNodal staging contributes to risk group definition and the indication to adjuvant treatment in endometrial cancer (EC) patients. However, the role of nodal assessment evolved and requires redefinition.Primary outcome of the study was to assess the impact of surgical nodal staging in defining high-risk (HR) EC. Secondary outcome was to evaluate the contribution of nodal assessment to the decision for adjuvant treatment in both high-risk and high-intermediate risk (HIR) patients submitted to surgery. MethodsClinical stage I-II EC patients with postoperative diagnosis of HR and HIR disease were included. The contribution of nodal staging in prognostic groups allocation was assessed by reviewing HR patients to identify those without any other feature of such class (non-endometrioid histology, p53abn immunohistochemistry, post-operative T3-T4 disease) and HIR cases to assess how nodal staging affected adjuvant treatment indication. Descriptive statistics were conducted to describe the two populations. ResultsFifty-seven patients were included, 46 with HR and 11 with HIR disease. Chemotherapy and external-beam radiotherapy (EBRT) were proposed in 40 HR patients. Considering histology, immunohistochemical profile and FIGO stage, high risk classification was exclusively relied on nodal involvement in 2/46 cases (4.3 %). Omitting retroperitoneal staging, one of them would have been classified in the intermediate risk group and the other as HIR: without nodal staging, chemotherapy and EBRT would have been omitted in 1/40 (2.5 %) case.Among HIR patients, chemotherapy was proposed in 7/11 cases and EBRT in all cases. Adjuvant chemotherapy was indicated in 5/6 (83.3 %) and omitted in 1/6 (16.7 %) pN0 patient (stage Ib G2, substantial LVSI). In HIRpN0 patients, omitting nodal staging could have changed adjuvant treatment indication in 1/6 (16.7 %) case. In HIRpNx patients, adjuvant chemotherapy was omitted in one patient (stage II, grade 2 and LVSI negative): nodal staging unavailability might have changed indication to chemotherapy in 1/5 (20 %) case, without changing indication to EBRT.Unavailable nodal staging could globally be related to omission of chemotherapy in 2/57 (3.5 %) patients and of EBRT in 1/57 (1.8 %) patient. ConclusionsIn this series, nodal staging had limited impact on definition of HR class and on the choice of adjuvant treatment in HR and HIR EC patients.

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

IntroductionThe 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. MethodsA 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. ResultsPostoperative 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. ConclusionsThe 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.

Accuracy of endometrial sampling in the diagnosis of endometrial cancer: a multicenter retrospective analysis of the JAGO-NOGGO

BackgroundAccurate preoperative molecular and histological risk stratification is essential for effective treatment planning in endometrial cancer. However, inconsistencies between pre- and postoperative tumor histology have been reported in previous studies. To address this issue and identify risk factors related to inaccurate histologic diagnosis after preoperative endometrial evaluation, we conducted this retrospective analysis.MethodsWe conducted a retrospective analysis involving 375 patients treated for primary endometrial cancer in five different gynaecological departments in Germany. Histological assessments of curettage and hysterectomy specimens were collected and evaluated.ResultsPreoperative histologic subtype was confirmed in 89.5% of cases and preoperative tumor grading in 75.2% of cases. Higher rates of histologic subtype variations (36.84%) were observed for non-endometrioid carcinomas. Non-endometrioid (OR 4.41) histology and high-grade (OR 8.37) carcinomas were identified as predictors of diverging histologic subtypes, while intermediate (OR 5.04) and high grading (OR 3.94) predicted diverging tumor grading.ConclusionWhen planning therapy for endometrial cancer, the limited accuracy of endometrial sampling, especially in case of non-endometrioid histology or high tumor grading, should be carefully considered.

Abstract A004: TP53 mutational landscape in non-cancerous endometrium during the lifespan of Black and White individuals

Abstract Background TP53 somatic mutations accumulate and clonally expand in histologically normal tissues with aging, however, little is known about this process and how it influences cancer development. Within endometrial carcinoma, TP53 mutations tend to be found in aggressive, non-endometrioid histologies associated with poor survival outcomes, more commonly affecting Black women. We seek to understand the TP53 mutational burden in benign endometrium by characterizing mutations acquired throughout a lifespan with the integration of social determinants of health in Black and White women. Methods Endometrial tissue was collected at autopsy or hysterectomy, confirmed with H&E staining, and macrodissected. Ultra-deep duplex sequencing (~10,000x) of isolated DNA was used to sequence TP53somatic mutations with high resolution. Each individual’s TP53 mutation frequency was calculated as the number of unique TP53 variants divided by the total duplex nucleotides sequenced. Mutations were classified as pathogenic if insertion-deletion, splice, or nonsense in addition to all pathogenic substitutions identified by the Seshat TP53 database. Socioeconomic metrics were acquired using zip codes and the 2021 US Census Bureau American Community Survey. Individuals with a history of endometriosis, prior malignancy, or prior chemotherapy were excluded. Results Benign endometrial tissue was collected from 69 individuals (24 Black, 45 White), including 22 aged 0-19 years, 25 aged 20-39 years, 17 aged 40-59 years, and 5 aged over 60 years. 174 TP53 variants were identified. Variant types included 66.7% missense (n=116), 13.2% insertion-deletion (n=23), 12.1% synonymous (n=21), 4.6% nonsense (n=8), and 3.4% splice (n=6). 102 TP53 mutations (58.6%) were pathogenic. TP53 mutation frequency increased linearly with age (Spearman correlation p<0.01). 12.6% of mutations were identified in more than one duplex mutant read (large clone) beginning at age 29 through age 81. The frequency of large TP53 mutant clones increased exponentially with age. In this limited dataset, there was no statistical association between socioeconomic metrics and the mutational burden of Black and White individuals. Conclusions The number and size of TP53 mutant clones in benign endometrium are associated with older age, indicating clonal evolution through life. Most somatic mutations identified were pathogenic substitutions or loss-of-function variants, confirming positive selection of cancer-like mutations. Additional data are needed to determine the role of socioeconomic factors in TP53 genomic burden. Citation Format: Eric Rios-Doria, Elizabeth U. Parker, Brendan F. Kohrn, Elena Latorre-Estevez, Jeanne Fredrickson, Elizabeth M. Swisher, Kemi M. Doll, Rosana Risques. TP53 mutational landscape in non-cancerous endometrium during the lifespan of Black and White individuals [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr A004.

Integration of pretreatment tumor markers in a nomogram model for prognostic prediction of FIGO stage I endometrial cancer: A multi-institutional cohort study.

Traditionally, the prognosis of patients with FIGO stage I endometrial cancer is determined by clinicopathological risk factors. In this study, we assessed the potential contribution of pretreatment carcinoembryonic antigen (CEA) and carbohydrate antigen-125 (CA-125) levels to estimating the prognosis of these patients and aimed to develop and validate a prognostic nomogram. This retrospective study included patients with FIGO stage I endometrial cancer who underwent treatment between January 2009 and December 2021 in the four institutes of Chang Gung Memorial Hospital. To identify optimal cutoff values of CEA and CA-125 for predicting survival, receiver operating characteristic (ROC) curves were generated, the Kaplan-Meier method was used to estimate survival, and a Cox regression model was used to analyze the independent prognostic factors. Finally, a nomogram and calibration curve were constructed to predict patient survival probability. Of the 1559 patients evaluated, the optimal cutoff values of CEA and CA-125 were 1.44 ng/mL (area under the ROC curve [AUC] 0.601) and 39.77 U/mL (AUC 0.503), respectively. Multivariate Cox regression analysis showed that pretreatment CEA (hazard ratio [HR] 2.11, 95% confidence interval [95% CI] 1.35-3.28), CA-125 (HR 2.07, 95% CI 1.31-3.27), age >70 years (HR 12.54, 95% CI 5.05-31.11), myometrial invasion >50% (HR 1.69, 95% CI 1.03-2.73), non-endometrioid histology (HR 1.83, 95% CI 1.14-2.95), high-grade tumor (HR 2.41, 95% CI 1.46-3.97), and lymphovascular space invasion (HR 2.32, 95% CI 1.26-4.25) were significant variables associated with overall survival. These factors were used to construct the nomogram model, which showed good concordance and accuracy. Integration of pretreatment CEA and CA-125 in a prognostic nomogram is feasible. Our prediction model has the potential to assist clinicians in guiding appropriate clinical practice.

Evaluation of factors influencing lymph node metastasis in endometrial cancers: A retrospective study.

The role of lymphadenectomy in the management of early endometrial cancer remains controversial. The aim of our study was to evaluate risk factors associated with nodal metastases in endometrial cancer and to devise a predictive risk model based on the significant risk factors in predicting node metastasis. A retrospective study was conducted on women diagnosed with uterus-confined endometrial cancer, and who underwent surgical staging with pelvic and/or paraaortic lymphadenectomy from our center during July 1, 2017 to June 30, 2019. Clinical details, Magnetic Resonance imaging (MRI)-detected myometrial invasion, and pre and post-operative histological details of tumor were correlated with pelvic and/or para-aortic lymph node metastasis. Risk factors were assessed using logistic regression model and risk models devised. 128 patients were included in the study. Paraaortic lymphadenectomy was done in 72.7% patients. Nodal metastasis was seen in 14.8% of patients. Logistic regression analyses revealed lymphovascular invasion (P = 0.002), parametrial involvement (P = 0.017) and nonendometrioid histology (P = 0.004) to be significant risk factors. Tumor size >2 cm, grade 3 and deep myometrial invasion had higher risk for nodal metastasis, although non-significant. Risk models were derived with sensitivity of 79-89.5%, specificity of 58.7-69.7%, Negative predictive value (NPV) of 95-97% and accuracy of 63-71%. Lymphovascular invasion, nonendometrioid histology and parametrial involvement are independent predictors of lymph node metastasis in endometrial cancer. Risk models using these risk factors can better predict the risk of nodal metastasis and thus avoid lymph node dissection in low risk patients. Our risk models had reasonably good sensitivity in nodal metastasis prediction and require further validation.

The Impact of Waiting Time-to-Surgery on Survival in Endometrial Cancer Patients.

Endometrial cancer (EC) is the most common gynecological cancer in developed countries and a standard treatment of surgery should be performed as expediently as possible. Delay time to surgery and survival was debated. The aim of this investigation was to evaluate the effect of time-interval between diagnosis and surgery (TDS) in EC patients with regards to prognosis and mortality rates. This retrospective study was conducted between January 2009 and May 2021 at Bhumibol Adulyadej Hospital, Thailand. Subjects were EC cases who underwent primary surgery during the study period. Cases with partial treatment were disqualified from the study. Subjects who underwent surgery before and after 6 weeks were classified as early and delayed surgery groups. Baseline and clinical characteristics were collected and analyzed. During the study period, 419 EC cases were recruited. The mean age of participants was 56.8 years. Two-thirds (338/491) of subjects were menopausal. Endometrioid histology (406/491) was the most common histology subtype. Five years disease free survival (DFS) of early and delayed surgery groups were comparable at a percentage of 82.5 and 83.0, respectively. Among advanced stage and non-endometrioid EC cases, the delayed surgery group had significantly shorter DFS than the early group. Advanced stage, high grade and positive lympho-vascular space invasion (LVSI) were independent factors for poor DFS. Predictive factors for mortality were advanced stage and tumor recurrence. The TDS was not a prognostic factor for disease recurrence or overall mortality. Time to surgery equal to or more than 6 weeks gave worse prognosis for DFS among advanced stage or non-endometrioid histology EC.

Exploring U.S. Hispanic origin groups diagnosed with uterine cancer - Are there disparities?

ObjectiveTo evaluate patterns and trends of uterine cancer among Hispanic subgroups. MethodsThe United States Cancer Statistics (USCS), National Cancer Database (NCDB), and World Population Review were used to obtain data on incidence, demographic characteristics, and cancer histology. Joinpoint regression program was used for statistical analysis. ResultsBased on 2001–2017 USCS data, the overall incidence of uterine cancer was 27.46 vs. 23.29/100,000 in Hispanics vs. non-Hispanic Whites. There was an over 2-fold higher annual increase in the incidence in Hispanics (1.94%; p < 0.001) vs. Whites (0.85%; p < 0.001), particularly in local stage disease. There was an increase in grade 1 endometrioid carcinoma (1.48%; p < 0.001 vs. −0.52%; p = 0.1) and aggressive histologic subtypes (4.04% p = 0.000 vs. 2.53% p = 0.000) in Hispanics vs. Whites.Using the NCDB (2004–2015), we analyzed 17,351 Hispanics by subgroup (Mexican, South/Central American, Puerto Rican, Cuban, and Dominican). Over the 12 years, there was an increase in the proportion of uterine cancer diagnoses in all Hispanics (5.2% to 11.0%; p < 0.0001). Dominican patients experienced the largest increase in diagnosis (2.6% to 14.9%; p < 0.0001), the highest proportion of advanced disease at 28.0% (p < 0.0001), and the highest incidence of non-endometrioid histologies at 37.1% (p < 0.0001).World Population Review 2023 revealed the highest female obesity rates in Puerto Rico (51.4%), the Dominican Republic (34.1%), and Mexico (32.8%). ConclusionUterine cancer incidence is increased in Hispanics, with the largest increase in Dominican women with more advanced stages and high-risk histologic subtypes. The impact of obesity on cancer risk, especially in Puerto Ricans, Dominicans, and Mexicans, warrants further investigation.

Oncologic Outcome of Robotic-Assisted and Laparoscopic Sentinel Node Biopsy in Endometrial Cancer.

Recently, sentinel lymph node biopsy (SLNB) has been introduced in the surgical staging of endometrial cancer as an alternative to systematic lymph node dissection (LND). However, the survival impact of SLNB is not yet well characterised. We performed a retrospective study of 419 patients with endometrial cancer treated with SLNB alone or with pelvic and para-aortic LND. For SLNB mapping, indocyanine green was used. Median follow-up was 66 months. After exclusions, 337 patients were eligible for analysis. Of them, 150 underwent SLNB and 187 LND. During the follow-up time, 27 (24.7%) of the 150 who underwent SLNB and 54 (28.9%) of the 187 who underwent LND were diagnosed with recurrent disease (p = 0.459). The estimated 5-year disease-free survival (DFS) rate was 76.7% and 72.2% for patients in the SLNB and LND group, respectively (p = 0.419). The 5-year overall survival (OS) rates were 80.7% and 77.0% in the SLNB and LND group, respectively (p = 0.895). Survival rates were similar in both groups independent of lymph node status. Multivariable analysis confirmed that the staging approach was not associated with oncological outcome. For patients without lymph node metastases, patient outcome was worsened by advanced tumour stage and non-endometrioid tumour histology. In the group of patients with confirmed lymph node metastases, advanced tumour stage and inadequate adjuvant treatment significantly reduced DFS and OS. Our data suggested that SLNB did not compromise the oncological outcome of patients with endometrial cancer compared to LND.

Comparing the survival rates of patients with stage IIIC endometrial cancer undergoing sandwich therapy to those undergoing sequential chemotherapy and radiotherapy: a meta-analysis.

The use of additional treatment after surgery for stage IIIC endometrial cancer (EC) according to the Federation of Gynecology and Obstetrics (FIGO) is still a topic of discussion. This meta-analysis examined the effects of sandwich treatment and sequential treatment on the survival of individuals diagnosed with stage IIIC EC. We examined the literature from various databases regarding the overall survival (OS) and adverse effects of the two additional therapies following surgery in individuals diagnosed with stage IIIC EC. Revman 5.4.1 was utilized to combine hazard ratios (HR) and their corresponding 95% confidence intervals (95% CI) for OS and toxicities. The findings comprised of five retrospective investigations involving a combined total of 800 individuals. The patients who underwent sandwich treatment did not demonstrate a notable improvement in survival rates over a period of 3years. Upon eliminating the impact of extensive samples, it was discovered that sandwich therapy exhibited a superior 5-year overall survival compared to patients receiving sequential therapy. The effectiveness of sandwich therapy was superior to sequential therapy in terms of a 3-year OS for non-endometrioid histology, although the outcome did not reach statistical significance. The toxicities of both treatments were similar. In terms of long-term survival, sandwich therapy was found to be more advantageous than sequential therapy for patients with stage IIIC EC, with no significant disparity observed in the 3-year OS and toxicities between the two treatments. Sandwich therapy exhibited a tendency towards improved effectiveness in patients with histology other than endometrioid.

Serum Proteomic Profiles of Patients with High and Low Risk of Endometrial Cancer Recurrence.

Endometrial cancer is the most common gynecological cancer worldwide. Classifying endometrial cancer into low- or high-risk groups based on the following features is recommended: tumor grade, lymphovascular space invasion, myometrial involvement, and non-endometrioid histology. Despite the recent progress in molecular profiling of endometrial cancer, a substantial group of patients are misclassified based on the current criteria. This study aimed to identify proteins that could be used as biomarkers for the stratification of endometrial cancer patients into low- or high-risk groups. The proteomic analysis of serum samples from endometrial cancer patients was performed using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). The data were then analyzed using chemometric algorithms to identify potential biomarkers. Nineteen precursor ions were identified as fragments of eighteen proteins which included (1) connective tissue matrix proteins, (2) cytoskeletal proteins, and (3) innate immune system molecules and stress proteins. These biomarkers could be used to stratify the high- and low-risk patients, thus enabling more precise treatment decisions.