High-risk Endometrial Cancer Patients Research Articles

The role of preoperative serum CA-125 levels in predicting lymph node metastasis in patients undergoing treatment for endometrial cancer

Aims: Endometrial cancer stands as the most prevalent gynecological malignancy in developed nations, often detected at an early stage, and generally carries a positive prognosis. The stage of the disease is important for survival, but many factors such as tumor grade, histopathology, myometrial invasion, age, and spread are also effective. Our objective was to assess the significance of preoperative Cancer antigen 125 (CA-125) concentrations in the prediction of lymph node metastasis in patients with endometrial cancer and to identify a suitable threshold value. Methods: This retrospective analysis was carried out on 286 female patients diagnosed with endometrial cancer at a specialized gynecologic oncology facility from 2012 to 2022. We examined clinical-pathological and demographic attributes, including preoperative serum CA-125 concentrations, surgical interventions conducted for each patient, post-treatment physical assessments, imaging findings, and cytological outcomes. CA-125 was measured using electrochemiluminescence immunoassay. Results: Statistically significant differences were observed in CA-125 levels among patients in terms of grade, invasion depth, lymph node involvement, cervical involvement, and stage (respectively, p<0.001, p=0.042, p<0.001, p<0.001, p<0.001). The FIGO advanced stage ratio was 30.6 times higher for serum CA-125 concentrations above the cutoff of 21 IU/ml (95% CI: 10.7-87.6) (p<0.001). Lymph node involvement was 29.7 times more likely for serum CA-125 values above the cutoff of 35 IU/ml (95% CI: 25.3-74.8) (p<0.001). Conclusion: Early identification of high-risk endometrial cancer patients is vital for prognosis and guiding adjuvant therapy. CA-125, a tumor marker, has been found useful in assessing myometrial invasion depth, lymph node involvement, stage differentiation, and tumor grade.

Comparison of immediate germline sequencing and multi-step screening for Lynch syndrome detection in high-risk endometrial and colorectal cancer patients.

Lynch syndrome (LS) is a hereditary cancer predisposition syndrome with a significantly increased risk of colorectal and endometrial cancers. Current standard practice involves universal screening for LS in patients with newly diagnosed colorectal or endometrial cancer using a multi-step screening protocol (MSP). However, MSP may not always accurately identify LS cases. To address this limitation, we compared the diagnostic performance of immediate germline sequencing (IGS) with MSP in a high-risk group. A total of 31 Taiwanese women with synchronous or metachronous endometrial and colorectal malignancies underwent MSP which included immunohistochemical staining of DNA mismatch repair (MMR) proteins, MLH1 promoter hypermethylation analysis, and germline sequencing to identify pathogenic variants. All patients who were excluded during MSP received germline sequencing for MMR genes to simulate IGS for the detection of LS. Our findings indicate that IGS surpassed MSP in terms of diagnostic yield (29.0% vs. 19.4%, respectively) and sensitivity (90% vs. 60%, respectively). Specifically, IGS successfully identified nine LS cases, which is 50% more than the number detected through MSP. Additionally, germline methylation analysis revealed one more LS case with constitutional MLH1 promoter hypermethylation, bringing the total LS cases to ten (32.3%). Intriguingly, we observed no significant differences in clinical characteristics or overall survival between patients with and without LS in our cohort. Our study suggests that IGS may potentially offer a more effective approach compared to MSP in identifying LS among high-risk patients. This advantage is evident when patients have been pre-selected utilizing specific clinical criteria.

Prognostic evaluation of the novel blueprint of DNA methylation sites by integrating bulk RNA-sequencing and methylation modification data in endometrial cancer.

Endometrial cancer (EC) is a prevalent malignancy affecting the female population, with an increasing incidence among younger age groups. DNA methylation, a common epigenetic modification, is well-established to play a key role in cancer progression. We suspected whether DNA methylation could be used as biomarkers for EC prognosis. In the present study, we analyzed bulk RNA-sequencing data from 544 EC patients and DNA methylation data from 430 EC patients in the TCGA-UCEC cohort. We applied weighted correlation network analysis to select a key gene set associated with panoptosis. We conducted correlation analysis between transcriptomic data of the selected key genes and DNA methylation data to identify valuable DNA methylation sites. These sites were further screened by Cox regression and least absolute shrinkage and selection operator analysis. Immune microenvironment differences between high-risk and low-risk groups were assessed using single-sample gene set enrichment analysi, xCell and MCPcounter algorithms. Our results identified five DNA methylation sites (cg03906681, cg04549977, cg06029846, cg10043253 and cg15658376) with significant prognostic value in EC. We constructed a prognostic model using these sites, demonstrating satisfactory predictive performance. The low-risk group showed higher immune cell infiltration. Notably, methylation of site cg03906681 was negatively related to CD8 T cell infiltration, whereas cg04549977 exhibited positive correlations with immune infiltration, particularly in macrophages, activated B cells, dendritic cells and myeloid-derived suppressor cells. PD0325901_1060 was strongly correlated with risk scores, indicating a potential therapeutic response for high-risk EC patients. We have developed a robust DNA methylation-based prognostic model for EC, which holds promise for improving prognosis prediction and personalized treatment approaches. These findings may contribute to better management of EC patients, particularly in identifying those at higher risk who may benefit from tailored interventions.

A patient-derived organoid-based study identified an ASO targeting SNORD14E for endometrial cancer through reducing aberrant FOXM1 Expression and β-catenin nuclear accumulation

BackgroundMost of the endometrial cancer (EC) patients are diagnosis in early stage with a good prognosis while the patients with locally advanced recurrent or metastatic result in a poor prognosis. Adjuvant therapy could benefit the prognosis of patients with high-risk factors. Unfortunately, the molecular classification of great prognostic value has not yet reached an agreement and need to be further refined. The present study aims to identify new targets that have prognostic value in EC based on the method of EC patient-derived organ-like organs (PDOs), and further investigate their efficacy and mechanism.MethodsThe Cancer Genome Atlas (TCGA) database was used to determine SNORD14E expression. The effects of SNORD14E were investigated using CCK8, Transwell, wound-healing assays, and a xenograft model experiment; apoptosis was measured by flow cytometry. Antisense oligonucleotide (ASO) targeting SNORD14E was designed and patient-derived organoids (PDO) models in EC patients was established. A xenograft mouse and PDO model were employed to evaluate the effects of ASO targeting SNORD14E. RNA-seq, Nm-seq, and RNA immunoprecipitation (RIP) experiments were employed to confirm the alternative splicing (AS) and modification induced by SNORD14E. A minigene reporter gene assay was conducted to confirm AS and splicing factors on a variable exon. Actinomycin-d (Act-D) and Reverse Transcription at Low deoxy-ribonucleoside triphosphate concentrations followed by PCR (RTL-P) were utilized to confirm the effects of 2′-O methylation modification on FOXM1.ResultsWe found that SNORD14E was overexpressed in EC tissues and patients with high expressed SNORD14E were distributed in the TCGA biomolecular classification subgroups without difference. Further, SNORD14E could reduce disease-free survival (DFS) and recurrence free survival (RFS) of EC patients. SNORD14E promoted proliferation, migration, and invasion and inhibited the apoptosis of EC cells in vitro. ASOs targeting SNORD14E inhibited cell proliferation, migration, invasion while promoted cell apoptosis. ASOs targeting SNORD14E inhibited tumor growth in the xenograft mouse model. TCGA-UCEC database showed that the proportion of patients with high expression of SNORD14E in middle-high risk and high-risk patients recommended by EMSO-ESGO-ESTRO guidelines for adjuvant therapy is more than 50%. Next, we enrolled 8 cases of high-risk and high-risk EC patients according to EMSO-ESGO-ESTRO guidelines and successfully constructed EC-PDOs. ASOs targeting SNORD14E inhibited the EC-PDO growth. Mechanistically, SNORD14E could recognize the mRNA of FOXM1 and recruit SRSF1 to promote the shearing of the variable exon VIIa of FOXM1, resulting in the overexpression of the FOXM1 malignant subtypes FOXM1b and FOXM1c. In addition, SNORD14E modified FOXM1 mRNA with 2`-O-methylation, which prolonged the half-life of FOXM1 mRNA. The nucleus accumulation of β-catenin caused by aberrant FOXM1 expression led to EC progression.ConclusionsASO targeting SNORD14E can be an effective treatment for EC.

Trends in use of radiation therapy, chemotherapy, and combination chemoradiotherapy in advanced uterine cancer before, during, and after GOG 258

ObjectiveTo explore the use of Gynecologic Oncology Group 258 (GOG 258) study regimens before, during, and after the study.MethodsPatients aged 18 years or older with endometrial cancer between 2004–2019 were...

RF3 Does the type of adjuvant radiation matter when treating elderly high-risk endometrial cancer patients with chemotherapy and radiation?

RF3 Does the type of adjuvant radiation matter when treating elderly high-risk endometrial cancer patients with chemotherapy and radiation?

Long-term survival outcomes in high-risk endometrial cancer patients undergoing sentinel lymph node biopsy alone versus lymphadenectomy

ObjectiveEndometrial cancer is the most common gynecologic neoplasm. To date, international guidelines recommend sentinel lymph node biopsy for low-risk neoplasms, while systematic lymphadenectomy is still considered for high-risk cases. This...

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.

Missing a chance to prevent: disparities in completion of genetic evaluation in high-risk patients with endometrial cancer.

The primary goal of this study is to examine disparities in high-risk endometrial cancer (EC) patients in relation to rates of genetic referrals (GR), testing (GT), and counseling (GC). This is a retrospective analysis of patients with newly diagnosed EC between January 1, 2014 and September 1, 2020 at a single institution. Patients were defined as high-risk EC patients when they were 1) diagnosed at 50 years or younger, 2) had a positive family history for cancer or 3) had evidence of loss of mismatch repair protein expression on tumor immunohistochemistry. Rates of GR, GT and GC were analyzed based on race, ethnicity, primary language and insurance status. During the study period, 674 patients were diagnosed with EC and 249 (36.9%) were considered high-risk EC patients. Among high-risk patients, 128 (51.2%) were referred to GT and GC. Of those referred, 103 (80.5%) underwent GT and 85 (66.4%) completed GC. Out of all high-risk patients, 20 (18.4%) were positive for LS on GT and 29 (28.2%) had VUS results. In multivariate analysis, the odds of GT and GC referral were lower among patients who identified as Hispanic (OR=0.40; 95% CI=0.19-0.87; p=0.020). Patients who identified as black were less likely to receive GC when compared to patients of other races (p=0.030). It is our hope that through this data we will increase awareness around existing disparities in genetic evaluation for patients with EC and ultimately create strategies to improve equitable access to care for all patients.

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.

Long-Term Follow-Up Results of Adjuvant Intensity-Modulated Radiotherapy with Concurrent Paclitaxel and Cisplatin in High-Risk Endometrial Cancer Patients.

Purpose The purpose of this study was to retrospectively review the outcomes of patients with high-risk endometrial cancer treated with adjuvant radiotherapy with concurrent paclitaxel and cisplatin (TP). Methods Patients with endometrial cancer who underwent radical surgery were screened between Jan 2005 and Dec 2018. Patients with high-risk factors who received adjuvant chemoradiotherapy were included in the study. High risks included stage I, endometrioid-type grade 3 with deep myometrial invasion or lymphovascular space invasion (or both), endometrioid-type stage II to IVa, or stage I to III with serous or clear cell histology. The adjuvant treatment regimen included one cycle of TP chemotherapy, followed by pelvic intensity-modulated radiotherapy (IMRT) with concurrent TP, followed by an additional one cycle of TP. Failure free survival (FFS) and overall survival (OS) were estimated. Patterns of recurrence and occurrence of adverse events were described. Results A total of 450 patients with high-risk endometrial cancer were screened, 231 of whom were included in this study. After a median follow-up of 70 months, the 5-year OS was 94.7%, and the 6-year OS was 91.8%. The 5-y and 6-y FFS were 90.8% and 87.9%, respectively, which were related to stage (P < 0.05). A total of 14 patients experienced tumor recurrence, including 7 pelvic recurrence and 7 distant metastases. Seven patients died, all due to tumor progression. A total of 164 patients (71%) completed the prescribed course of treatment. A total of 205 patients had adverse events, 46 patients (20%) had grade 1, 92 patients (40%) had grade 2, 49 patients (21%) had grade 3, and 18 patients (8%) had grade 4. There were 83 nonhematologic and 122 hematologic toxicities (26 grade 3 and 18 grade 4). Conclusion Adjuvant pelvic radiotherapy combined with synchronous TP chemotherapy can achieve excellent long-term survival for high-risk endometrial cancer patients. Moreover, this combination therapy has good safety and feasibility, which is worthy of further study and verification.

Disparities in completion of genetic testing and counseling for Lynch syndrome in high-risk patients diagnosed with endometrial cancer (601)

Disparities in completion of genetic testing and counseling for Lynch syndrome in high-risk patients diagnosed with endometrial cancer (601)

Minimally invasive surgery versus open surgery in high-risk histologic endometrial cancer patients: A meta-analysis

ObjectiveTo compare the effects of minimally invasive surgery (MIS) and open surgery (OPS) on the risk of recurrence and mortality in patients with endometrial cancer (EC) of high-risk histology (grade 3 endometrioid adenocarcinoma, papillary serous carcinoma [PS], clear cell carcinoma [CC], and carcinosarcoma) using meta-analysis. Material and methodsWe systematically reviewed published studies comparing MIS and OPS in EC patients with high-risk histology until January 2022. The endpoints were recurrence and mortality rate. Study design features that may have affected participant selection, recurrence/death detection, and manuscript publication were assessed. For pooled estimates of the effect of MIS on recurrence/mortality, the random- or fixed-effects meta-analytical models were used after assessing the cross-study heterogeneity. ResultNine observational studies (eight retrospective and one prospective) fulfilled our search criteria (MIS, 8877 patients; OPS, 5751 patients). The fixed-effects model-based meta-analysis indicated that MIS did not significantly increase the risk of recurrence (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.71–1.05; p = 0.13) and mortality (HR, 0.86; 95% CI, 0.79–0.93; p < 0.001) when compared with OPS. This pattern was also observed in the subgroup analyses based on the stage (early stage vs. all stage), histology (PS and CC), and MIS type (laparoscopy vs. robotic). There was no evidence of publication bias. ConclusionThis meta-analysis of observational studies revealed that MIS did not compromise the prognosis of EC patients with high-risk histology. Well-designed randomized controlled trials could verify the results of this uncommon but deadly tumor.

The Feasibility of Sentinel Lymph-Node, Mapped with Indocyanine Green, Biopsy in Endometrial Cancer Patients: A Prospective Study

Background and objectives. Systematic pelvic lymphadenectomy (LND) is an essential part of lymph-node status evaluation in endometrial cancer (EC) patients to tailor the adjuvant treatment. However, it is associated with the post-operative lymphatic complications and does not improve the outcomes of the disease. Indocyanine green (ICG) mapped sentinel lymph-node biopsy (SLB) has recently been introduced into the clinical practice as an alternative for the surgical lymph-node evaluation in EC patients with the potential to decrease LND related complications. The aim of our study was to evaluate the feasibility of ICG mapped SLB in low, intermediate, and high-risk EC patients in a center with no previous experience on endoscopic SLB procedure. Materials and Methods: The prospective study was performed. 170 patients with histologically confirmed EC were included. Sentinel lymph-nodes (SLs) were mapped with ICG dye and removed ahead of the total laparoscopic hysterectomy. Low-risk patients received only SLB, while SLB and LND were performed for intermediate and high-risk patients. Results: The overall detection rate of SLs was 88.8%. Bilateral mapping was achieved in 68.2% of the patients. The overall detection rate for low-risk patients was 93.7%, 85.0% for the intermediate-risk group, and 100% for high-risk patients (p = 0.232). The most common anatomical sites of SLs were the external iliac (45.8% on the right and 46.6% on the left) and obturator regions (20.9% and 25.6%, respectively). Positive lymph-nodes were found in 8 (4.7%) patients. The sensitivity of SLB was 75.0% and negative predictive value (NPV)—97.2%. Conclusions: Even in the center with no previous experience, sentinel lymph-node biopsy using ICG mapping is feasible. However, the favorable outcomes might be associated with the learning process of newly established method.

Similar distribution of pelvic sentinel lymph nodes and nodal metastases in cervical and endometrial cancer. A prospective study based on lymphatic anatomy

ObjectiveComparing the anatomical distribution of metastatic and non-metastatic pelvic sentinel lymph nodes (SLN) in cervical and endometrial cancer. MethodsDetailed SLN mapping results were prospectively retrieved in cervical (n = 145) or high-risk endometrial cancer (n = 201) patients undergoing a robotic staging procedure. Cervically injected Indocyanine Green (ICG), allowing for reinjection in case of inadequate mapping, was used as tracer. An anatomically based definition of SLNs was adhered to evaluating the upper (UPP) and lower (LPP) paracervical lymphatic pathways. The positions of SLNs were intraoperatively depicted on an anatomical chart. A completory pelvic lymphadenectomy was performed. Mapping rates and anatomical distribution of SLNs and the location of pelvic nodal metastases were compared between groups. ResultsThe bilateral mapping rate was 97.9% and 95.0% for cervical and endometrial cancer respectively (p = .16). The proportion of typically positioned (interiliac and proximal obturator fossa) SLNs along the UPP was similar between groups (78.1% vs 82.1%, p = .09), and the rate of metastatic SLNs in the obturator fossa was 54.1% and 48.6% respectively (p = .45). All pelvic node positive women (cervical cancer n = 19, endometrial cancer n = 37) had at least one metastatic SLN. Anatomically typical positions could not be defined along the LPP. ConclusionThe anatomical location of SLNs and SLN metastases are similar in cervical and endometrial cancer suggesting that sensitivity results for an SLN concept in endometrial cancer and cervical cancer can be accumulated.

Minimally invasive surgery in gynecological cancers: update and systematic review

Introduction: In the last decades, the introduction of laparoscopy and, more recently, of robotic surgery, offered new options for surgical treatment also in gynecological malignancies, as an alternative to open surgery. When considering the best surgical treatment option for gynecological malignancies, evidence about safety, feasibility, and oncological outcomes must be taken into account, to offer the best treatment to the patient. The present review aims to provide an updated scenario over the available evidence in the use of minimally invasive surgery (MIS) in gynecological malignancies. Material and methods: An electronic search was performed using the following keywords: ‘minimally invasive surgery’ and ‘gynecology’, ‘minimally invasive surgery’ and ‘endometrial cancer’, ‘minimally invasive surgery’ and ‘ovarian cancer’, ‘minimally invasive surgery’ and ‘cervical cancer’. The agreement about potential relevance was reached by consensus of the researchers and according to PRISMA statement guidelines. Systematic reviews, meta-analyses, clinical trials, and original articles were included in the present review. Results: Fifty-eight studies were considered eligible for the study, 23 studies regarding MIS in endometrial cancer (EC), 19 studies on MIS in ovarian cancer (OC), and 16 studies regarding MIS in cervical cancer (CC). The total of patients enrolled was 180,057, 131,430 in the EC group, 23,774 in the OC groups, and 24,853 in the CC group. Conclusions: According to the available evidence and current clinical practice, MIS is undoubtedly the gold standard for early-stage EC treatment and may represent an acceptable option even in high-risk EC patients. Concerning OC, MIS is a safe and useful tool for staging purposes in advanced-stage disease, and a treatment option only in high volume centres with expert oncologic surgeons. On the contrary, MIS should be abandoned in the context of CC, exception made for well-selected patients, who received adequate counselling about current evidence.

Diagnostic accuracy of sentinel node biopsy in non-endometrioid, high-grade and/or deep myoinvasive endometrial cancer: A Turkish gynecologic oncology group study (TRSGO-SLN-006)

IntroductionThis study aimed to evaluate the diagnostic accuracy of the sentinel lymph node (SLN) mapping algorithm in high-risk endometrial cancer patients. MethodsTwo hundred forty-four patients with non-endometrioid histology, grade 3 endometrioid tumors and/or tumors with deep myometrial invasion were enrolled in this retrospective, multicentric study. After removal of SLNs, all patients underwent pelvic ± paraaortic lymphadenectomy. Operations were performed via laparotomy, laparoscopy or robotic surgery. Indocyanine green (ICG) and methylene blue (MB) were used as tracers. SLN detection rate, sensitivity, negative predictive value (NPV) and false-negative rate (FNR) were calculated. ResultsSurgeries were performed via laparotomy in 132 (54.1%) patients and 152 (62.3%) underwent both bilateral pelvic and paraaortic lymphadenectomy. At least 1 SLN was detected in 222 (91%) patients. Fifty-five (22.5%) patients had lymphatic metastasis and 45 patients had at least 1 metastatic SLN. Lymphatic metastases were detected by side-specific lymphadenectomy in 8 patients and 2 patients had isolated paraaortic metastasis. Overall sensitivity, NPV and FNR of SLN biopsy were 81.8%, 95% and 18.2%, respectively. By applying SLN algorithm steps, sensitivity and NPV improved to 96.4% and 98.9%, respectively. For grade 3 tumors, sensitivity, NPV and FNR of the SLN algorithm were 97.1%, 98.9% and 2.9%. ConclusionSLN algorithm had high diagnostic accuracy in high-risk endometrial cancer. All pelvic metastases were detected by the SLN algorithm and the isolated paraaortic metastasis rate was ignorable. But long-term survival studies are necessary before this approach becomes standard of care.

Can addition of frozen section analysis to preoperative endometrial biopsy and MRI improve identification of high-risk endometrial cancer patients?

BackgroundSurgeons sometimes have difficulty determining which result to favor when preoperative results (MRI + preoperative endometrial biopsy [pre-op EB]) differ from intraoperative frozen section histology (FS) results. Investigation of how FS can complement ordinary preoperative examinations like MRI and pre-op EB in identification of patients at high risk of lymph node metastasis (high-risk patients) could provide clarity on this issue. Therefore, the aim of this study is to assess the utility of pre-op EB, MRI and FS results and determine how to combine these results in identification of high-risk patients.MethodsThe subjects were 172 patients with endometrial cancer. Patients with a histological high-grade tumor (HGT), namely, grade 3 endometrioid cancer, clear cell carcinoma or serous cell carcinoma, or with any type of cancer invading at least half of the uterine myometrium were considered high-risk. Tumors invading at least half of the uterine myometrium were classified as high-stage tumors (HST). We compared (a) detection of HGT using pre-op EB versus FS, (b) detection of HST using MRI versus FS, and (c) identification of high-risk patients using MRI + pre-op EB versus FS. Lastly, we determined to what degree addition of FS results improves identification of high-risk patients by routine MRI + pre-op EB.Results(a) Sensitivity, specificity, and accuracy for detecting HGT were 59.6, 98.4 and 87.8% for pre-op EB versus 55.3, 99.2 and 87.2% for FS (P = 0.44). (b) These figures for detecting HST were 74.4, 83.0 and 80.8% for MRI versus 46.5, 99.2 and 86.0% for FS (P < 0.001). (c) These figures for identifying high-risk patients were 78.3, 85.4 and 82.6% for MRI + pre-op EB versus 55.1, 99.0 and 81.2% for FS (P < 0.001). The high specificity of FS improved the sensitivity of MRI + pre-op EB from 78.3 to 81.2%, but this difference was not statistically significant (P < 0.16).ConclusionFrozen section enables identification of high-risk patients with nearly 100% specificity. This advantage can be used to improve sensitivity for identification of high-risk patients by routine MRI + pre-op EB, although this improvement is not statistically significant.

Factors predicting morbidity in surgically-staged high-risk endometrial cancer patients

ObjectiveTo investigate factors predicting the risk of developing 90-day postoperative complications and lymphatic-specific morbidity in patients undergoing surgical staging for high-risk endometrial cancer. MethodsThis is a multi-institutional retrospective cohort study. Patients affected by apparent early-stage high-risk endometrial cancer (endometrioid FIGO grade 3 with deep myometrial invasion and non-endometrioid endometrial cancer) undergoing surgical staging between 2007 and 2019. Complications were graded according to the Clavien-Dindo classification system. Martin criteria were applied to improve quality of complications reporting. ResultsCharts of 279 patients were evaluated. Lymphadenectomy, sentinel node mapping (SNM), and SNM followed by back-up lymphadenectomy were performed in 83 (29.7%), 50 (17.9%), and 146 (52.4%) patients, respectively. The former group of patients included 13 patients who had lymphadenectomy after the failure of the SNM technique. Thirteen (4.6%) patients developed severe postoperative events (grade 3 or worse). At multivariate analysis, body mass index (OR: 1.08 (95%CI: 1.01, 1.17)) and open abdominal surgery (OR: 2.27 (95%CI: 1.02, 5.32)) were the two independent factors predictive of surgery-related morbidity. Seven severe lymphatic complications occurred. The adoption of laparoscopic approach (p < 0.001, log-rank test) and SNM (p = 0.038, log-rank test) correlated with a lower risk of developing surgery-related events. Independently, open abdominal surgery was associated with an increased risk of developing lymphatic morbidity (OR: 37.4 (95%CI: 4.38, 319.5); p = 0.001). ConclusionThe adoption of the laparoscopic approach and SNM technique were associated with lower 90-day complication rates than open surgery in high-risk endometrial cancer undergoing staging surgery.

Safe obturator nerve identification during pelvic lymphadenectomy for high-risk endometrial cancer—a case report

Background: Endometrial cancer (EC) is the most frequent gynecological cancer and the fourth in western women. To date, although the sentinel lymph node technique is the gold standard in low-risk EC patients, pelvic and lumboaortic lymphadenectomy is still suggested by international guidelines for staging purposes in high-risk EC patients. Pelvic lymphadenectomy is burdened by surgical complications ranging from vascular, nerve, intestinal, and lymphatic-related injuries. Furthermore, due to its proximity to the large pelvic vessels, the obturator nerve is the most frequently injured in gynecological surgery. The identification of the obturator nerve can take place either through the mediolateral approach through the lateral paravesical fossa or with a lateromedial approach through the iliolumbar fossa. To date, no specific approach is recommended and each surgeon will perform the approach they are most confident with.