Management Of Endometrial Cancer Research Articles

RACCE Study: Impact of an enhanced recovery after surgery program (ERAS) in the management of endometrial cancer: A single-center retrospective study

ObjectiveThis study evaluates the implementation of an ERAS program in the gynecological surgery department of Caen University Hospital and its impact on the management of endometrial cancer.The objective was to show its impact on the length of hospitalization of patients before and after its implementation. Patients and methodWe conducted a retrospective study including all women treated surgically for endometrial cancer at Caen University Hospital between January 1, 2015 and December 31, 2021. The ERAS program started in September 2017.We compared the pre-, intra- and postoperative characteristics of two groups: the first one concerning the period before the implementation of ERAS called « prior ERAS group » and the second one after implementation called « post ERAS group ». ResultsA total of 198 patients were included in our study. 139 patients were included after ERAS implementation. Our study shows that there is a significant reduction in median length of stay between the post ERAS and prior ERAS groups respectively 3 and 4 days (p = 0.004). There was also a reduction of time to resume ambulation (p < 0.001) and re-feeding (p < 0.001) for the post ERAS group compared to the prior ERAS group. Complication rates (p = 0.87) and readmission rates (p = 0.28) were not significant. Overall survival was not significant (p = 0.28). ConclusionERAS is a safe and effective method in the overall management of patients allowing an improvement in the quality of patient care and accelerating recovery to a previous physiological state. Finally, this results in a reduction in the patient's length of stay, without impacting morbidity and readmission rate.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with endometrial cancer

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with endometrial cancer was published in 2022. It was therefore decided, by both the ESMO and the Indian Society of Medical and Paediatric Oncology (ISMPO), to convene a virtual meeting in July 2022 to adapt the ESMO 2022 guidelines to take into account the variations in the management of endometrial cancer in Asia. These guidelines represent the consensus opinion of a panel of Asian experts representing the oncological societies of China (CSCO), India (ISMPO), Indonesia (ISHMO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO). Voting was based on scientific evidence and was conducted independently of the current treatment practices and treatment access constraints in the different Asian countries, which were discussed when appropriate. The aim of this guideline manuscript is to provide guidance for the optimisation and harmonisation of the management of patients with endometrial cancer across the different regions of Asia, drawing on the evidence provided by Western and Asian trials whilst respecting the variations in clinical presentation, diagnostic practices including molecular profiling and disparities in access to therapeutic options, including drug approvals and reimbursement strategies.

Sentinel Lymph Node Biopsy in Uterine Cancer: Time for a Modern Approach.

Since the validation of the sentinel node technique (SLN) for vulvar cancer 20 years ago, this technique has been introduced in the management of operable cervical cancer and endometrial cancer. For cervical cancer a "one fits all" attitude has mainly been presented. However, this approach, consisting of a frozen section during the operation, can be discussed in some stages. We present and discuss the main option for each stage, as well as some secondary possibilities. For endometrial cancer, SLN is now the technique of choice for the nodal staging of low- and intermediate-risk groups. Some discussion exists for the high-risk group. We also discuss the impacts of using preoperatively the molecular classification of endometrial cancer. Patients with POLE or TP53 mutations could have different nodal staging. The story of SLN in uterine cancers is not finished. We propose a comprehensive algorithm of SLN in early cervical and endometrial cancers. However, several ongoing trials will give us important data in the coming years. They could substantially change these propositions.

Pattern of practice for postoperative management of endometrial cancer in Korea: a survey by the Korean Gynecologic Oncology Group and the Korean Radiation Oncology Group (KGOG 2028-KROG 2104).

This study aimed to investigate the current status of postoperative management of uterine endometrial cancer (EC) in Korea. A mail survey was administered to members of the Korean Gynecologic Oncology Group and Korean Radiation Oncology Group. A total of 38 gynecologic cancer surgeons (GYNs) and 31 radiation oncologists (RO) in 43 institutions was responded. The questionnaire consisted of general questions for clinical decision and clinical case questions. The GYN and RO responses were compared using chi-square statistics. The 2 expert groups had similar responses for clinical decision based on the results of the Gynecologic Oncology Group (GOG)-249 and Postoperative Radiation Therapy for Endometrial Carcinoma-III trials in the early-stage EC. In contrast, the responses based on GOG-258 results differed, as GYNs most frequently opted for sequential chemotherapy (CTx) and radiotherapy (RT), while ROs preferred concurrent chemoradiotherapy in locally advanced stage (p<0.05). Based on the GOG-258, GYNs preferred CTx alone for adjuvant treatment of serous or clear cell adenocarcinoma histology, whereas ROs advocated for combined CTx and RT (sequential or concurrent). Among the clinical case questions, GYNs were more likely than ROs to choose CTx alone rather than the combination of CTx and RT (sequential or concurrent) as the answers to case questions representing patients with locally advanced stage or unfavorable histology (all p<0.05). The present study showed several different opinions of GYNs and ROs regarding adjuvant treatment for EC, particularly for adjuvant RT in advanced stage or unfavorable histology.

The Glutaminase Inhibitor Compound 968 Exhibits Potent In vitro and In vivo Anti-tumor Effects in Endometrial Cancer.

Glutamine is one of the primary nutrients utilized by cancer cells for energy production and biosynthesis. Hence, interfering with glutamine metabolism may impose anti-tumor effects. In this study, we assessed the anti-tumorigenic effects of glutaminase-1 enzyme (GLS1) inhibition in endometrial cancer in vitro and in vivo. The human endometrial cancer cell lines Ishikawa and HEC-1B were used. The effects of compound 968 on cell proliferation, cell cycle, apoptosis, cellular stress, and AKT/mTOR pathway inhibition were assessed. The synergistic effects of compound 968 and paclitaxel were also analyzed. The in vivo effect of compound 968 was evaluated using tumor xenografts. We found that the GLS1-targeting compound 968 was able to reduce cancer cell proliferation in a dose- and time-dependent manner. Compound 968 combined with a low concentration of paclitaxel showed stronger inhibitory effects. Further analyses indicated that compound 968 induced cell cycle arrest at the G1 phase, as well as increased the production of cellular reactive oxygen species (ROS) and promoted cellular stress and cancer cell apoptosis. Additionally, the treatment of endometrial cancer with compound 968 downregulated the expression of GLS1 and cyclin D1 and upregulated the expression of P21 and E-cadherin. Moreover, the treatment of endometrial cancer cells with compound 968 significantly reduced the levels of phospho-S6 ribosomal protein and phospho-AKT (Ser473), indicative of AKT/mTOR/S6 signaling pathway inhibition. In xenograft mouse models of endometrial cancer, compound 968 significantly suppressed tumor growth. In addition, western blotting analysis indicated that GLS1 expression was upregulated in human endometrial cancer tissues. Compound 968 may be a promising approach for the management of human endometrial cancer.

Sentinel Lymph Node Mapping in Presumed Low- and Intermediate-Risk Endometrial Cancer Management (SLIM): A Multicenter, Prospective Cohort Study in The Netherlands.

The aim was to investigate the incidence of sentinel lymph node (SLN) metastases and the contribution of SLN mapping in presumed low- and intermediate-risk endometrial cancer (EC). A multicenter, prospective cohort study in presumed low- and intermediate-risk EC patients was performed. Patients underwent SLN mapping using cervical injections of indocyanine green and a minimally invasive hysterectomy with bilateral salpingo-oophorectomy. The primary outcome was the incidence of SLN metastases, leading to adjusted adjuvant treatment. Secondary outcomes were the SLN detection rate and the occurrence of complications. Descriptive statistics and univariate general linear model analyses were used. A total of 152 patients were enrolled, with overall and bilateral SLN detection rates of 91% and 61%, respectively. At final histology, 78.9% of patients (n = 120) had truly low- and intermediate-risk EC. Macro- and micro-metastases were present in 11.2% (n = 17/152), and three patients had isolated tumor cells (2.0%). Nine patients (5.9%) had addition of adjuvant radiotherapy based on SLN metastases only. In 2.0% of patients with high-risk disease, adjuvant therapy was more limited due to negative SLNs. This study emphasizes the importance of SLN mapping in presumed early-stage, grade 1 and 2 EC, leading to individualized adjuvant management, resulting in less undertreatment and overtreatment.

Assessment of Hospital Volume in the Surgical Management of Endometrial and Ovarian Cancer: A Polish Population-Based Study.

BACKGROUND Surgery is a cornerstone in management of ovarian and endometrial cancer. The European Society of Gynecological Oncology introduced quality indicators to improve management of these cancers. The optimal annual number of surgeries per unit was established for high-quality surgical treatment. MATERIAL AND METHODS The database of the National Health Fund on surgical management of endometrial and ovarian cancer was analyzed. Patients treated between 2017 and 2020 were included. Departments where patients underwent surgery were divided according to number of surgeries performed per year in endometrial cancer: ≥80, 79-50, 49-20, 19-0; and ovarian cancer: ≥100, 99-50, 49-20, 19-0. Optimal number of surgeries per center was defined as at least 100 and 80 surgeries per year in ovarian and endometrial cancer, respectively. RESULTS Totally, there were 22 325 surgeries in 316 units and 10 381 surgeries in 251 units due to endometrial and ovarian cancer, respectively. Most surgeries in endometrial cancer (n=15 077; 67.5%) and ovarian cancer (n=9642; 92.88%) were performed in departments that did not meet optimal criteria in number of surgeries. Between 2017 and 2019, an increasing trend in number of surgeries per year in endometrial and ovarian cancer was found. In 2020, there was a decrease in the number of surgeries by 7.8% (n=453) and 8.6% (n=234) in endometrial and ovarian cancer, respectively. CONCLUSIONS In Poland, surgical treatment of ovarian and endometrial cancer is decentralized. Most cancer patients underwent surgery in low-volume general gynecologic departments. The COVID-19 pandemic impaired cancer management, leading to a decreased number of surgeries.

Safety of laparoscopic surgery in the management of endometrioid endometrial cancer.

Laparoscopic surgery has increasingly been preferred in recent years. However, data regarding the safety of laparoscopy in endometrial cancer are not sufficient. The aim of this study was to compare perioperative and oncologic outcomes of laparoscopic and laparotomic staging surgery in patients with endometrioid endometrial cancer and to evaluate the safety and efficacy of laparoscopic surgery in this population. Data of 278 patients, who underwent surgical staging for endometrioid endometrial cancer at the gynecologic oncology department of a university hospital between 2012 and 2019, were analyzed retrospectively. Demographic, histopathologic, perioperative, and oncologic characteristics were compared between laparoscopy and laparotomy groups. A subgroup of patients with a body mass index (BMI) >30 was further evaluated. Demographic and histopathologic characteristics were similar between the two groups, while laparoscopic surgery was seen to be significantly superior in terms of perioperative outcomes. The number of removed and metastatic lymph nodes was significantly higher in the laparotomy group; however, this difference did not affect the oncologic outcomes, including recurrence and survival rates, and the two groups had similar results in this aspect. The outcomes of the subgroup with BMI >30 were also in accordance with the whole population. Intraoperative complications in laparoscopy were managed successfully. Laparoscopic surgery appears to be advantageous over laparotomy, and depending on the surgical experience, it may be performed safely for surgical staging of endometrioid endometrial cancer.

Management of Endometrial Cancer: French Society of Onco-Gynecology's Evaluation through a Delphi Survey.

Our aim was to assess the opinion of a panel of experts and obtain a consensus on the management of endometrial cancer in France and French Switzerland. A Delphi survey was carried out among a panel of French and French-speaking Swiss experts. The first questionnaire included 65 questions divided into eight categories: characterization of experts, histo-molecular characteristics and radiological data of endometrial cancer, and management of low-risk, intermediate-risk, intermediate-high-risk, high-risk, and metastatic cancers. The experts were asked to reply on a 9-point scale, both on the validity and the clarity of each question. After the answers were analyzed, a second questionnaire was sent to the same experts. The study took place between December 2021 and March 2022. Further, 58 (57.4%) of the 101 experts responded in the first round, and 39 recommendations were obtained (60%). Six questions were voted redundant and 20 discordant. These questions were reformulated, and, at the end of the second round, 17 recommendations were validated (85%). In total, the study presents an analysis of 56 questions and related responses. Expert advice helps to clarify non-consensual issues, standardize the management of endometrial cancer, and optimize clinical practices.

Generation and Integrated Analysis of Advanced Patient-Derived Orthoxenograft Models (PDOX) for the Rational Assessment of Targeted Therapies in Endometrial Cancer.

Clinical management of endometrial cancer (EC) is handicapped by the limited availability of second line treatments and bona fide molecular biomarkers to predict recurrence. These limitations have hampered the treatment of these patients, whose survival rates have not improved over the last four decades. The advent of coordinated studies such as The Cancer Genome Atlas Uterine Corpus Endometrial Carcinoma (TCGA_UCEC) has partially solved this issue, but the lack of proper experimental systems still represents a bottleneck that precludes translational studies from successful clinical testing in EC patients. Within this context, the first study reporting the generation of a collection of endometrioid-EC-patient-derived orthoxenograft (PDOX) mouse models is presented that is believed to overcome these experimental constraints and pave the way toward state-of-the-art precision medicine in EC. The collection of primary tumors and derived PDOXs is characterized through an integrative approach based on transcriptomics, mutational profiles, and morphological analysis; and it is demonstrated that EC tumors engrafted in the mouse uterus retain the main molecular and morphological features from analogous tumor donors. Finally, the molecular properties of these tumors are harnessed to assess the therapeutic potential of trastuzumab, a human epidermal growth factor receptor 2 (HER2) inhibitor with growing interest in EC, using patient-derived organotypic multicellular tumor spheroids and in vivo experiments.

Endometrial Cancer in Reproductive Age: Fertility-Sparing Approach and Reproductive Outcomes.

Endometrial cancer is the most common gynecologic malignancy in developed countries and approximately 7% of the women with endometrial cancer are below the age of 45. Management of endometrial cancer in young women who desire to maintain fertility presents a unique set of challenges since the standard surgical treatment based on hysterectomy and salpingo-oophorectomy is often not compatible with the patient's goals. A fertility-preserving approach can be considered in selected patients with early stage and low-grade endometrial cancer. An increasing amount of data suggest that oncologic outcomes are not compromised if a conservative approach is utilized with close monitoring until childbearing is completed. If a fertility-preserving approach is not possible, assisted reproductive technologies can assist patients in achieving their fertility goals.

Long-Term Results Following Use of Vaginal Electronic Brachytherapy in the Management of Endometrial Cancer

<h3>Purpose/Objective(s)</h3> We evaluated long-term vaginal toxicity and disease outcomes in women treated with vaginal electronic brachytherapy (EBT) following surgical management of endometrial cancer. <h3>Materials/Methods</h3> Women with endometrial cancer treated with adjuvant EBT were included in this study. Women diagnosed with uterine cancer of high-risk histology or advanced stage received EBT following completion of adjuvant chemotherapy. EBT was performed using a miniature low-energy (50-kV peak) X-ray source with a single-channel vaginal cylinder applicator to deliver radiation to the vagina along a specified length of the cylinder. EBT was delivered either as monotherapy or as a sequential boost following completion of pelvic external beam radiation (EBRT). EBT was delivered to 4 cm treatment length prescribed as 7 Gy to 5 mm depth x 3 fractions in the EBT alone group or 6 Gy to vaginal surface x 3 fractions in the EBT boost group. Following completion of EBT, patients were evaluated for all toxicities and recurrences. In this study, we evaluated for treatment related vaginal toxicity (stenosis) which was scored according to the Common Terminology Criteria for Adverse Events version 5.0. Multivariable analysis (MVA) of prognostic factors was performed using Cox Proportional-Hazards Model, and disease-free survival (DFS) and overall survival (OS) were estimated from date of surgery with Kaplan-Meier Method using data management and decision management software. <h3>Results</h3> 70 women were treated from 12/2017-6/2020 with EBT following hysterectomy. Median age of the cohort was 68 years (range, 51-85 years). 37 presented with endometrioid histologies. 32 received adjuvant chemotherapy prior to EBT. 21 presented with stage II or greater disease, and 20 received EBRT prior to EBT boost. EBT was delivered over a median interval of 1.3 weeks (range, 0.3-3.1 weeks). At a median follow-up of 25.0 months (range, 7.2-47.4 months), no patients were found to have ≥ grade 3 vaginal toxicity. The cumulative risk of developing gr 1 and 2 vaginal toxicity at 30 months was 25%. Prescription to 5 mm depth was the only factor associated with development of vaginal toxicity (p<0.05). One vaginal cuff recurrence, one locoregional recurrence, and ten distant recurrences were observed. Advanced tumor stage, high-risk histology, cervical stroma involvement, treatment with chemotherapy, and treatment with EBRT were significantly associated with inferior DFS/OS on MVA. DFS and OS in this group at 12 and 36 months were 94.2%/69.4% and 95.7%/88.3%, respectively. <h3>Conclusion</h3> EBT appears to be a safe, well-tolerated, and a promising alternative treatment option to traditional vaginal brachytherapy using a radioactive source. On MVA, prescription of EBT to 5 mm depth was associated with vaginal stenosis. One local recurrence was observed at 25 months follow-up. Risk of developing vaginal toxicity, DFS, and OS, following treatment with EBT in this heterogeneous population appear to be acceptable and comparable to historical controls (PORTEC 2 PMID 20206777).

27P Clinical relevance of NGS analysis in endometrial cancer (EC) management

After the introduction of the molecular classification in EC guidelines, Next Generation Sequencing (NGS) analysis has become an essential tool for EC management. Molecular-driven therapies have also been recently tested, and some have obtained FDA approval. This retrospective cohort study aims to determine the clinical benefit rate (CBR) with the use of targeted therapies based on NGS in ECs patients.

Does the character of the hospital of primary management influence outcomes in patients treated for presumed early stage endometrial cancer and atypical endometrial hyperplasia: a comparison of outcomes from a cancer unit and cancer centre

A retrospective study from 2015 to 2020 comparing overall survival (OS) outcomes of a cancer unit and centre for presumed early stage endometrial cancers is presented. Cancer centres manage these presumed early endometrial cancer (EC) in situations of complex co-morbidities, surgical challenges as well as their own local unit patients. Our analysis compares 138 patients at KMH (unit) and 282 patients at RDH (centre) on OS, patient demographics, grading histology and final histology. Patients with presumed early stage EC can be reassured regarding no difference in OS between the cancer unit and centre management (p = .05). However, rates of minimal access surgery were higher at the cancer centre compared to the unit (93.2% versus 68.1%). The rates of upstaged disease were 4% and 8.8% at the cancer unit and centre respectively (p = .096). Sentinel node biopsy and genomic assessment may change future thresholds for centre-level management due to rates of upstaged disease. Impact Statement What is already known on this subject? Presumed lower risk endometrial cancers (endometrioid grades 1 and 2) have a rate of occult nodal involvement of only 1.4%. The BGCS does not recommend lymphadenectomy for low-risk endometrial cancers. These low-risk endometrial cancers should be managed with a hysterectomy and bilateral salpingo-ophrectomy via minimal access surgery. In view of the low rates of occult nodal involvement in low-risk endometrial cancer, surgery can be offered at a cancer unit. What do the results of this study add? Our study demonstrates there is no disadvantage in overall survival in the surgical management of presumed low-risk endometrial cancers at cancer units and centres. However, cancer centres have higher rates of minimal access to surgery despite managing a more elderly population. Our rates of upstaged disease of 4% and 8.8% at the cancer unit and centre indicate a potential benefit of pelvic lymph node assessment. What are the implications of these findings for clinical practice and/or further research? Sentinel lymph node biopsy does not have the surgical morbidity associated with systematic lymph node dissection. Therefore, when applied to presumed early stage endometrial cancer, there are potential changes in the threshold for centre-level management to improve overall survival.

Conservative Management of Atypical Endometrial Hyperplasia and Early Endometrial Cancer in Childbearing Age Women.

Total hysterectomy and bilateral adnexectomy is the standard treatment for atypical endometrial hyperplasia and early-stage endometrial cancer. However, the recommended surgical treatment precludes future pregnancy when these conditions are diagnosed in women in their fertile age. In these patients, fertility-sparing treatment may be feasible if the desire for childbearing is consistent and specific conditions are present. This review summarizes the available evidence on fertility-sparing management for atypical endometrial hyperplasia and early-stage endometrial cancer. Historically, oral progestins have been the mainstay of conservative management for atypical endometrial hyperplasia and stage IA endometrioid endometrial cancer with no myometrial invasion, although there is no consensus on dosage and treatment length. Intrauterine progestin therapy has proved a valid alternative option when oral progestins are not tolerated. GnRH analogs, metformin, and hysteroscopic resection in combination with progestins appear to increase the overall efficacy of the treatment. After a complete response, conception is recommended; alternatively, maintenance therapy with strict follow-up has been proposed to decrease recurrence. The risk of disease progression is not negligible, and clinicians should not overlook the risk of hereditary forms of the disease in young patients, in particular, Lynch syndrome. Hysterectomy is performed once the desire for childbearing desire has been established. The conservative management of atypical endometrial hyperplasia and early-stage endometrial cancer is feasible, provided a strong desire for childbearing and permitting clinical–pathological conditions. However, patients must be aware of the need for a strict follow-up and the risk of progression with a possible consequent worsening of the prognosis. More homogenous and well-designed studies are necessary to standardize and identify the best treatment and follow-up protocols.

Less is more in endometrial cancer (SLN, conservative treatment, radical hysterectomy, molecular classification).

The management of endometrial cancer has known many evolutions within the last decades. In this review, we aim to summarize recent evolutions (mainly toward less aggressive management) that have occurred in the management of endometrial cancer. Enhanced by molecular classification, the determination of lymph node status, in young women, in case of cervical invasion, the treatment is evolving toward a less aggressive strategy. The predictive value and the safety of sentinel lymph node biopsy explain why most societies propose to abandon systematic pelvic and para aortic lymphadenectomy. For young women, the safety of fertility preservation is now well established and efficient protocols have been validated. In stage II endometrial cancer (stromal cervical invasion), radical hysterectomy appears excessive. The Cancer Genome Atlas classification increases prognostic evaluation in association with the traditional pathological classification and permits to tailor adjuvant treatment more accurately.

Association of immunohistochemical profiles with histotypes in endometrial carcinomas

ObjectiveAlthough a large number of endometrial cancer patients are cured with surgery alone, there are significant numbers of patients with more aggressive variants of endometrial carcinoma for whom the prognosis remains poor. We investigated the effects of prevalence, histotypes, and immunohistochemical profiles on prognostic value in a hospital-based population. Materials and methodsA retrospective study of surgically resected primary endometrial carcinoma was included. Immunohistochemical stains were performed on formalin-fixed paraffin-embedded tissue microarray sections for β-Catenin, estrogen receptor (ER), progesterone receptor (PR), HER-2, MLH1, MSH2, MSH6, PMS2, and p53. ResultsLoss of mismatch repair expression was detected in 25.4% of samples (29/114, mean age 57 years) of the tumors. The following loss of expression was observed in patients: MLH1/PMS2 in 16.6% of patients, MSH6 in 7.0% of patients, MLH1 in 0.9% of patients, and MSH6/PMS2/MLH1 in 0.9% of patients. Immunohistochemistry of p53 was analyzed for 111 patients. A total of 13 patients (11.7%, mean age 64 years) had p53-abnormal expression (absent, cytoplasmic or diffuse strong positive patterns), and more than half (9/13, 69.2%) had endometrioid histotype. Abnormalities in p53 were significantly associated with histotype (p = 0.001), advanced tumor stage (p = 0.038), death of disease (p = 0.002), PR percentage (p = 0.002), and HER-2 expression (p = 0.018). Immunohistochemical nuclear localization of β-Catenin was detected in 7.1% of the cohort. The combination of p53 and nuclear β-Catenin expressions was not significantly predictive of disease-free or overall survival. ConclusionThe results of this study are useful for management of endometrial cancer in patients with DNA mismatch repair, abnormal p53 expression, or nuclear localization of β-Catenin.

Safety and efficacy of levonorgestrel-releasing intrauterine device in the treatment of atypical endometrial hyperplasia and early endometrial cancer.

To investigate the recurrence rate, live-birth rate, and treatment outcomes of levonorgestrel-releasing intrauterine device (LNG-IUD) for the management of atypical endometrial hyperplasia (AEH) or Grade-1 endometrial cancer (EC) in patients who desire fertility-sparing treatment and those seeking conservative treatment without fertility preservation. We prospectively enrolled nine patients from a single institution between April 2009 and September 2013 who were followed up for 60 months after LNG-IUD insertion. The median patient age was 35 (range: 29-39) years. The overall recurrence rate was 56% (5/9). The median interval between removal of the LNG-IUD and recurrence was 20.5 (range: 2-30) months. Three of the nine patients had Grade-1 EC, and six had AEH. The response rates to the LNG-IUD in patients with Grade-1 EC and AEH were 66% and 100%, respectively. Four patients (three with AEH, one with Grade-1 EC) experienced recurrence 6 months after MPA treatment and all 4 (100%) had complete response. Eight patients desired fertility preservation, of which 37% (3/8) conceived after receiving fertility treatment and 25% (2/8) had a live birth; the remaining three had previously received MPA for 6 months and had a recurrence; of these, 1 had a live birth. LNG-IUD is effective for the management of AEH and EC in young patients who desire fertility-sparing treatment, including those ineligible for MPA owing to the presence of comorbidities and those with recurrence after MPA treatment (6-month treatment), and patients seeking conservative treatment without fertility preservation.

Cancer de l’endomètre de stade localisé : la perspective d’une désescalade thérapeutique guidée par la classification moléculaire

In Europe, endometrial cancer is the fourth most common cancer among women. The majority of patients are diagnosed at a localized stage. For these patients, the standard of care is based on an hysterectomy with salpingo oophorectomy±lymph node staging. Through the assessment of histopathologic features, risk groups are determined: low, intermediate, high-intermediate, and high risk. Adjuvant strategies are guided by these risk groups. While the prognosis of low-risk and high-risk is well known, that of intermediate and high-intermediate risk is more heterogeneous, and the therapeutic index of adjuvant treatments is more questionable. Several trials (PORTEC [Post Operative Radiation Therapy in Endometrial Carcinoma] I, GOG [Gynecologic Oncology Group] 99, ASTEC [A Study in the Treatment of Endometrial Cancer] EN.5, PORTEC II, Sorbe et al trial) have assessed observation, vaginal cuff brachytherapy and/or pelvic external beam radiotherapy in this population. Vaginal cuff brachytherapy reduces the local recurrence rate, and pelvic external beam radiotherapy the pelvic recurrence rate. However, no benefit in terms of overall survival or occurrence of distant metastases is highlighted. Compared to observation, brachytherapy and above all external beam radiotherapy are associated with an increased morbidity, and with a decreased quality of life. In order to improve the therapeutic ratio and to optimize medico-economic decisions, therapeutic de-escalation strategies, based on the molecular profiles, are emerging in clinical trials, and in the recommendations for the management of intermediate and high-intermediate risk endometrial cancers. The four main molecular profiles highlighted by the genomic analyzes of The Cancer Genome Atlas (TCGA) – POLE (polymerase epsilon) mutation, non-specific molecular profile, MMR (MisMatch repair) deficiency, and p53 mutation – but also the quantification of lymphovascular space invasion (absent, focal or substantial), and the assessment of L1CAM (L1 cell adhesion molecule) overexpression represent growing concerns. Thus, the use of molecular-integrated risk profile to determine the best adjuvant treatment represent a major way to personalize adjuvant treatment of endometrial cancers, with therapeutic de-escalation opportunity for around half of the high-intermediate risks. However, in the absence of prospective data, inclusion in clinical trials assessing molecular profile-based treatment remains the best therapeutic opportunity.

Impact of pre-treatment prognostic nutritional index and the haemoglobin, albumin, lymphocyte and platelet (HALP) score on endometrial cancer survival: A prospective database analysis

PurposeThe Onodera’s prognostic nutritional index (PNI) and the haemoglobin, albumin, lymphocyte and platelet (HALP) score are immune-nutritional indices that correlate with survival outcomes in several adult solid malignancies. The aim of this study was to investigate whether PNI and HALP are associated with survival outcomes in endometrial cancer.Patients and methodsWomen undergoing management for endometrial cancer were recruited to a single centre prospective cohort study. Pre-treatment PNI and HALP scores were computed for study participants and analysed as continuous variables and by selecting cut-off values based on previous publications. Both parameters were analysed in relation to overall, endometrial cancer-specific and recurrence-free survival using Kaplan-Meier estimation and multivariable Cox proportional regression.ResultsA total of 439 women, with a median age of 67 years (interquartile range (IQR), 58, 74) and BMI of 31kg/m2 (IQR 26, 37) were included in the analysis. Most had low-grade (63.3%), early-stage (84.4% stage I/II) endometrial cancer of endometrioid histological subtype (72.7%). Primary treatment was surgery in 98.2% of cases. Adjusted overall mortality hazard ratios for PNI and HALP as continuous variables were 0.97(95%CI 0.94–1.00, p = 0.136) and 0.99(95%CI 0.98–1.01, p = 0.368), respectively. Women with pre-treatment PNI ≥45 had a 45% decrease in both overall (adjusted HR = 0.55, 95% CI 0.33–0.92, p = 0.022) and cancer-specific mortality risk (adjusted HR = 0.55, 95%CI 0.30–0.99, p = 0.048) compared to those with PNI <45. There was no evidence for an effect of PNI on recurrence free survival. HALP scores were associated with adverse clinico-pathologic factors, but not overall, cancer-specific or recurrence-free survival in the multivariable analysis.ConclusionPNI is an independent prognostic factor in endometrial cancer and has the potential to refine pre-operative risk assessment.