Management Of Endometrial Cancer Research Articles

Tailored Therapy Based on Molecular Characteristics in Endometrial Cancer.

Management of endometrial cancer, an adenocarcinoma of the endometrium which occupies most uterine corpus neoplasms, including uterine sarcomas, has been more relevant due to its increasing incidence. Extensive research on tumorigenesis molecular mechanisms and molecular characterization across cancers has brought paradigm shifts in the treatment of various malignant tumors. Endometrial cancer treatment has been traditionally guided according to the disease extent or histology types, while recent studies on molecular features have led to the introduction of targeted agents into clinical use, along with conventional chemotherapeutic agents in patients with recurrent or metastatic disease. Considering the proven efficacy and relatively tolerable toxicities of targeted therapies across malignant tumors, improvement of treatment outcomes is also expected in endometrial cancer by adopting an individualized therapy depending on the specific molecular features. Efficacy assessment of new biological agents is still ongoing based on previous preclinical data on endometrial cancer molecular features. Here, endometrial cancer molecular characterization will be reviewed, and then, we will introduce preclinical data, directing the adoption of new biological agents.

Status of Sentinel Lymph Node Biopsy in Endometrial Cancer.

The role of lymphadenectomy in surgical staging remains one of the biggest controversies in the management of endometrial cancer. The concept of sentinel lymph node biopsy in endometrial cancer has been evaluated for a number of years, with promising sensitivity rates and negative predictive values. The possibility of adequate staging while avoiding systematic lymphadenectomy leads to a significant reduction in the rate of peri- and postoperative morbidity. Nevertheless, the status of sentinel lymph node biopsy in endometrial cancer has not yet been fully elucidated and is variously assessed internationally. According to current European guidelines and recommendations, sentinel lymph node biopsy in endometrial cancer should be performed only in the context of clinical studies. In this review article, the developments of the past decade are explored concisely. In addition, current data regarding the technical aspects, accuracy and prognostic relevance of sentinel lymph node biopsy are explained and evaluated critically.

Economic evaluation of different routes of surgery for the management of endometrial cancer: a retrospective cohort study

ObjectivesThe benefits of minimally invasive surgery (MIS) for endometrial carcinoma (EC) are well established although the financial impact of robotic-assisted hysterectomy (RH) compared with laparoscopic hysterectomy (LH) is disputed.DesignRetrospective cohort...

FDG-PET/CT and Para-Aortic Staging in Endometrial Cancer. A French Multicentric Study.

Background: FDG-PET/CT is a noninvasive examination that could be helpful for the management of endometrial cancer. The aim of this study was to evaluate the performance of FDG-PET/CT in assessing para-aortic lymph-node involvement in high-risk endometrial cancer. Methods: We performed a retrospective multicenter study including all patients who had a high-risk endometrial cancer with a preoperative FDG-PET/CT and a para-aortic lymphadenectomy (PAL) between 2009 and 2019. The main objective was to evaluate the overall performance of FDG-PET/CT. The secondary objectives were to evaluate its performances according to the histological type and according to FDG-PET/CT date (before or after hysterectomy), and to compare its overall performance with that of the MRI scan. Results: We included 200 patients from six different centers. After the false positive FDG-PET/CT was reread by nuclear physicians, FDG-PET/CT had a sensitivity of 61.8%, a specificity of 89.7%, a positive predictive value of 69.4%, a negative predictive value of 86.1%, and an AUC of 0.76. There were no statistically significant differences in the performances according to either histological type and or FDG-PET/CT date. The sensitivity of FDG-PET/CT was better than that of MRI (p < 0.01), but the specificity was not (p = 0.82). Conclusion: Currently, FDG-PET/CT alone cannot replace PAL for the lymph node evaluation of high-risk endometrial cancers. It seems essential to reread it in multidisciplinary meetings before validating the therapeutic management of patients, particularly in the case of isolated para-aortic involvement.

Multiparametric magnetic resonance imaging facilitates the selection of patients prior to fertility-sparing management of endometrial cancer.

To compare the diagnostic performance of biparametric magnetic resonance imaging (bpMRI) versus multiparametric MRI (mpMRI) for the staging of well-differentiated endometrioid endometrial cancer (EC) in potential candidates for fertility-sparing management. This multi-center retrospective study included 48 potential candidates for fertility-sparing management (age <46 years, grade 1 endometroid EC) who did not wish to undergo fertility-sparing management and thus underwent definitive surgery. Two readers (R1, R2) independently reviewed bpMRI (T1, T2, and diffusion-weighted imaging) and mpMRI (bpMRI and dynamic contrast-enhanced imaging, DCE) during two separate sessions spaced one month apart for the presence of myometrial invasion (MI), cervical stromal involvement (CSI), malignant adnexal disease (mAD), and pelvic lymphadenopathy (pLNM). Each reader also recorded maximum tumor diameter, tumor volume, and tumor-to-uterine volume ratio (TVR) on T2-weighted imaging. The diagnostic performance of bpMRI and mpMRI was determined for each reader with surgical pathology serving as a gold standard. The area under the receiver operating curve (AUC) for bpMRI versus mpMRI was 0.76/0.78 (R1/R2) versus 0.84/0.83 for MI, 0.79/0.76 versus 0.99/0.80 for CSI, 0.84/0.84 versus 0.84/0.80 for mAD, and 0.82/0.82 for pLMN. The sensitivity and specificity of MRI for detecting tumor spread beyond the endometrium were 71%/77% and 71%/65% for bpMRI (R1/R2) vs. 84%/90% and 71%/65% for mpMRI (R1/R2), respectively. The AUC of maximum tumor diameter, tumor volume, and TVR for MI was 0.71/0.61, 0.73/0.75, and 0.75/0.77 for R1/R2, respectively. MRI had moderate diagnostic performance across potential candidates for fertility-sparing treatment of EC. mpMRI outperformed bpMRI for detecting EC spreading beyond the endometrium.

Fertility preserving management of early endometrial cancer in a patient cohort at the department of women\u2019s health at the university of Tuebingen

PurposeTo investigate the oncologic and reproductive outcome of a conservative treatment with progestin agents in early-stage grade 1 endometrial cancer (G1EC), grade 2 endometrial cancer (G2EC) or complex atypical hyperplasia (CAH) in young premenopausal women.MethodsWomen treated for early-stage endometrial cancer or atypical hyperplasia of the endometrium with a conservative therapy between 2006 and 2018 were enrolled in this retrospective analysis. Progestin agents were orally administered on a daily basis for 3 months for at least one cycle. Endometrial tissue was obtained by hysteroscopy and Dilatation & Curettage (D&C) being performed before and after end of treatment. Therapeutic response was assessed by pathological examination.ResultsA total of 14 patients were included. After treatment with progestin agents, 11 of these patients initially showed a complete or partial response. Three patients with early-stage endometrial cancer did not respond.Of the three patients with initially diagnosed atypical hyperplasia, none showed any remaining disease later. Of the eight patients with initially diagnosed endometrial cancer, who had responded to first treatment, three patients were re-diagnosed with endometrial cancer later. One patient with initial endometrial cancer became pregnant but aborted in the 10th week.ConclusionDue to its good efficacy, progestin agents offer a feasible therapeutic option in the fertility-preserving treatment of early-stage endometrial cancer in young premenopausal women. However, recurrence rate remains high. Therefore, a close follow-up is mandatory, also in responders. Patients should be informed of limitations and risks of conservative treatment. Yet after completion of family planning, hysterectomy should be performed.

Palliative treatment of endometrial cancer: what is the role of anastrozole in elderly women?

BackgroundType I endometrial cancer is the most common gynaecological tumour in developed countries and its incidence is increasing also because of population aging. The aim of this work is to test the feasibility and safety of anastrozole as palliative treatment of endometrial cancer in elderly women ineligible for standard surgical treatment.MethodsPatients with histological diagnosis of type I endometrial cancer not suitable for surgical treatment were enrolled in this pilot study. Anastrozole was administered 1 mg daily orally after performing an accurate clinical and radiological staging. Validated questionnaire and self-reported outcomes were used to evaluate quality of life and compliance during the study period.ResultsEight patients with a mean age of 85 (range 80–88 years) were enrolled. All patients had endometrial cancer confined to the uterus, and none progression of disease was observed during the study period. A partial response to the therapy was reported in seven patients, while one patient had stable disease. Tumour symptoms improvement such as pain, vaginal bleeding and vaginal discomfort was reported. The endometrial thickness after twelve months has showed a reduction of 9.25 ± 4.77 mm. The average follow-up time was 18.25 months. Four women died for non oncological reasons, none death related to endometrial cancer was reported. Evaluation of symptoms showed a significant reduction of appetite loss and insomnia, while a significant increase of global health status and fatigue was reported.ConclusionsOur preliminary data suggested that the palliative use of anastrozole may be a suitable therapy for the proper management of early stages endometrial cancer in elderly women not suitable for surgical treatment with good compliance and tolerance.Trial registration2013000840. Date of registration: 21/09/2013. URL: trials.sanmatteo.loc.

Prognostic value of serum HE4 level in the management of endometrial cancer: A pilot study.

Human epididymis protein 4 (HE4) has shown promising utility as a prognostic biomarker in endometrial cancer. Increased serum HE4 levels may be associated with deeper myometrial invasion, extrauterine disease and poorer prognosis. To evaluate the use of serum HE4 level, compared to and alongside other investigations, to accurately guide management in apparent early-stage endometrial cancer. This is a single-site prospective study of 100 patients with histologically confirmed endometrial cancer. All patients underwent preoperative measurements of HE4 and CA125 levels and a preoperative magnetic resonance imaging (MRI) to assess the depth of invasion, nodal status and tumour size. Correlation was sought between serum HE4 level, CA125 level, MRI findings and intra-operative frozen section with tumour type, grade and stage. While both median HE4 and CA125 levels were higher with worsening clinicopathological features, serum HE4 level showed a more consistent association with high-risk features. Patients with a low-grade biopsy preoperatively and a low HE4 level (<70pmol/L) demonstrated an 86.8% likelihood of having low-risk disease on final histopathology. In comparison, preoperative MRI or intraoperative frozen section alongside a low-grade biopsy demonstrated a similar likelihood of 86.2 and 87.7%, respectively. When used in conjunction with an initial low-grade endometrial biopsy, serum HE4 level demonstrated a similar likelihood to both preoperative MRI and intraoperative frozen section in identifying low-risk disease on final histopathology. As a triaging tool this may be significant given that a preoperative, serum-based assay would likely be the least invasive, least resource-intensive and most cost-effective approach.

Robotic platforms for endometrial cancer treatment: review of the literature.

The cornerstone in the management of endometrial cancer (EC) is surgical staging. Over the last few decades, minimally invasive surgery has been widely accepted as a mainstay in the treatment of endometrial cancer. The first robotic-assisted gynecological surgery was performed in 1998. The literature search was conducted using MEDLINE, EMBASE and PUBMED databases from January 1998 to September 2020. Several studies have reported the advantages of robotic-assisted surgery over laparoscopy in the management of EC. These are most pronounced in obese patients. Robotic-assisted surgery is also associated with a shorter learning curve, particularly for lymphadenectomy, which enables more surgeons to perform minimally invasive surgery for EC. The effectiveness and oncological results of robotic surgery for EC appear to be similar to those of other surgical methods, but fewer intraoperative complications occur than with other methods.

Risk Factors for Surgical Treatment of Endometrial Cancer Using Traditional and Laparoscopic Methods.

Surgical treatment is the most important part of therapy for endometrial cancer. The aim of the study was to define factors having the most significant impact on surgical treatment of endometrial cancer when using traditional and laparoscopic methods. In the study, we evaluated 75 females who were treated for endometrial cancer via laparoscopic surgery in 2019 and used a historical control of 70 patients treated by laparotomy in 2011. The evaluated risk factors included the method of surgery, type of lymphadenectomy, patient’s age, various obesity parameters, histological grading, cancer clinical staging, pelvic dimensions, previous abdominal surgeries, comorbidities, and number of deliveries. The duration of hospitalization, operation time, loss of hemoglobin, and procedure-related complications were used as parameters of perioperative outcomes. Multivariable linear regression analysis confirmed the following factors as being predictors of worse perioperative outcomes: laparotomy, abdominal obesity (waist circumstance and waist-to-hip ratio), range of lymphadenectomy, prior abdominal surgeries, and larger pelvic dimensions. Abdominal obesity is a significant risk factor in the treatment of endometrial cancer. Laparotomy continues to be utilized frequently in the management of endometrial cancer in Poland as well as elsewhere, and adopting a minimally invasive approach is likely to be beneficial for patient outcome.

Two-port access for laparoscopic surgery for endometrial cancer using conventional laparoscopic instruments

Minimally invasive surgery is the first-line management for endometrial cancer. The role of 2-port access laparoscopy (TPA) has been underestimated. Compared to conventional laparoscopic surgery (CL), TPA is associated with smaller total incision size and less postoperative pain. Compared to single-incision laparoscopic surgery, no specific instruments and surgical techniques are needed. This study primarily evaluated the surgical and pathologic outcomes of TPA with conventional instruments, and additionally evaluated the surgeon’s learning curve. Consecutive patients who underwent TPA and CL for endometrial cancer between 2015 and 2019 were included. Baseline characteristics were recorded. In total, 148 patients (TPA, 89; CL, 59) were identified. The baseline characteristics were similar, except for a greater proportion of patients in the CL group receiving para-aortic lymph node dissection (5.62% vs. 35.59%, P < 0.01). The mean operation time was significantly less in the TPA group (152.09 vs. 187.15 min; P < 0.01). Both the groups had comparable 5-year progression-free survival (TPA, 86.68%) and 5-year overall survival rates (TPA, 93.24%). Analysis of the learning curve showed that the operation time decreased after 3–4 procedures. TPA using conventional laparoscopic instruments for endometrial cancer is feasible and is easily accessible to patients and surgeons.

Controversies in the Management of Early-stage Serous Endometrial Cancer

Early-stage uterine serous carcinoma (USC) has one of the highest recurrence rates and mortality among early-stage uterine epithelial cancers. Research into the clinical management of USC has begun to progress, guided by surgical and pathological advances. This article summarizes the available literature regarding diagnosis, management, and possible future uses of molecular analysis of women with early-stage USC. PubMed was searched for all pertinent English language research articles published from January 1, 2006 through March 1, 2020 which included a study population of women diagnosed with stage 1 USC. Due to the scarcity of prospective or large-scale data, studies were not limited by design or numbers of patients. Studies performed at earlier dates were incorporated to provide context. A total of 86 studies were included in the review. Multiple well-designed studies have confirmed the safety of a minimally invasive surgical approach for surgical management of USC. The role of sentinel node biopsy has been validated with both prospective and retrospective multi-center data. Stage I USC is associated with a highly variable risk of recurrence, even following completion of adjuvant chemoradiation. This aggressive phenotype has been linked to high numbers of somatic copy number alterations, tumor protein 53, and phosphatidylinositol 3 kinase mutations, which have been shown to be predictive of prognosis. Early-stage USC demonstrates a lack of predictable recurrence patterns, with reports noting distant recurrence in patients with disease confined to polyps. Unless no residual tumor is found on hysterectomy, chemotherapy and radiotherapy should be discussed and individualized by stage and treatment goals.

A comparison of various endometrial cancer management guidelines

A comparison of various endometrial cancer management guidelines

Practice patterns for Lynch syndrome-associated endometrial cancer management in Korea

Practice patterns for Lynch syndrome-associated endometrial cancer management in Korea

Management of endometrial cancer: an update to a gynaecologist

Endometrial carcinoma, the most common gynaecological malignancy in high income countries and increasingly rising in low-middle income countries, has a predominantly favorable outcome. Although the majority of cases of endometrial cancer are diagnosed at an early stage, differences in patient characteristics and histopathological features of the disease impact on both patient prognosis and the recommended treatment approach. Irrespective of the vast literature on the different management options for endometrial cancer, this article gives an updated summary on management principles to a practicing gynaecologist.

Hysteroscopy in the management of endometrial hyperplasia and cancer in reproductive aged women: new developments and current perspectives.

Over the last twenty years, the incidence of early endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) among women of reproductive age is increasing rapidly, likely due to a combination of factors including increased prevalence of obesity and delayed of childbirths. Regarding preoperative diagnosis of endometrial neoplasia, it is still debated which is the most accurate and reliable method to obtain endometrial histopathological samples with fractional dilatation and curettage (D&C) having been considered, for a long time, as the method of choice. Nowadays, the advent of in-office endometrial biopsy with or without hysteroscopy has radically changed the approach, giving the opportunity to perform the endometrial biopsy under direct visualization. However, the lack of agreement about its diagnostic accuracy is still relevant. Since a significant number of women with AEH and/or EC are of childbearing age, a fertility-sparing diagnostic and therapeutic approach should be considered in all cases. The feasibility, safety and efficacy of fertility-sparing strategies involving hysteroscopic focal resections in conjunction with hormonal therapies have been evaluated and beneficial effects have been confirmed in several studies and one meta-analysis. Both local and systemic administration of hormonal therapies are currently used. Oral progestin, including medroxyprogesterone acetate (MPA) and megestrol acetate, are the most commonly used therapies. Nowadays, new therapeutic approaches, such as levonorgestrel intrauterine systems (LNG-IUS), gonadotropin-releasing hormone (GnRH) agonists, combined megestrol acetate and metformin, and other combinations of therapies are also used as first line therapies or after the hysteroscopic resection of the lesion. However, it is still unclear which approach provides higher clinical response with lower relapse rate, in addition to preserving fertility in women desiring to conceive. The aim of this narrative review is to summarize the available evidence regarding the evaluation and management with fertility-sparing treatments options of women with AEC and EC.

Fertility-sparing management for endometrial cancer: review of the literature.

Primary surgery is effective in low-risk endometrial cancer (EC). However, in young women, this approach compromises fertility. Therefore, fertility-sparing management in the case of atypical endometrial hyperplasia, or grade 1 EC limited to the endometrium can be considered. We performed a literature review to identify studies involving women with EC or atypical hyperplasia who underwent fertility-sparing management. We conducted multiple bibliographic databases research from their inception to May 2020. Oral therapy with medroxyprogesterone acetate and megestrol acetate is recommended based on extensive experience, although without consensus on dosages and treatment length. The pooled complete response rate, recurrence rate, and pregnancy rate of EC were 76.3%, 30.7% and 52.1%, respectively. Endometrial hyperplasia was associated with better outcomes. LNG-IUSs appears an alternative treatment, particularly in patients who do not tolerate oral therapy. In a randomized controlled trial, megestrol acetate plus metformin guaranteed an earlier complete response rate than megestrol acetate alone for endometrial hyperplasia. Hysteroscopic resection followed by progestogens is associated with a higher complete response rate, live birth rate, and lower recurrence rate than oral progestogens alone. Pooled complete response, recurrence, and live birth rates were 98.1%, 4.8% and 52.6%. Fertility preservation appears feasible in young patients with grade 1 EC limited to the endometrium or atypical endometrial hyperplasia. Progestins are the mainstay of such management. The addition of Metformin and hysteroscopic resection seems to provide some improvements. However, fertility preservation is not the standard approach for staging and treatment, potentially worsening oncologic outcomes.

Mismatch repair status influences response to fertility-sparing treatment of endometrial cancer

Patients younger than 40 years usually present with early-stage endometrial cancer with favorable prognosis. However, such patients are usually in their childbearing age and may desire fertility-sparing options. The identification of biomarkers may improve the clinical outcomes in these patients and aid in fertility-sparing management; however, there has been no reports on biomarker analysis so far. This study aimed to evaluate the prognostic significance of Proactive Molecular Risk Classifier for Endometrial Cancer in the fertility-sparing management of endometrial cancer. A total of 57 endometrial biopsy specimens obtained before hormone therapy were evaluated, and patients were classified according to the Proactive Molecular Risk Classifier for Endometrial Cancer molecular subtypes (mismatch repair deficiency, DNA polymerase epsilon mutation, wild-type p53, and abnormal p53). The primary endpoint was the response rate after hormone therapy. The secondary endpoint was the recurrence rate after the complete response, hysterectomy rate owing to treatment failure, and upstaged diagnosis rate after hysterectomy. Of 57 patients, 9 (15.8%) had mismatch repair deficiency, 2 (3.5%) had DNA polymerase epsilon mutation, 45 (78.9%) had wild-type p53, and 1 (1.8%) had abnormal p53. Overall, the complete response rate was 75.4% after hormone therapy. Patients with mismatch repair deficiency had a significantly lower complete response or partial response rate than those with wild-type p53 in terms of the best overall response (44.4% [95% confidence interval, 4.0-85.0] vs 82.2% [95% confidence interval, 71.0-94.0]; P=.018) and complete response rate at 6 months (11.1% [95% confidence interval, 0.2-37.0] vs 53.3% [95% confidence interval, 38.0-68.0]; P=.010). Among patients with mismatch repair deficiency, 4 underwent immediate hysterectomy because of treatment failure and 3 presented upstaged diagnosis after hysterectomy. The Proactive Molecular Risk Classifier for Endometrial Cancer molecular classification has prognostic significance in the fertility-sparing management of endometrial cancer, thereby enabling early stratification and risk assignment to direct care. Mismatch repair status could be used as a predictive biomarker for selecting patients who could benefit from hormone therapy. These findings need to be validated in larger studies.

Therapeutic potential of a novel prodrug of green tea extract in induction of apoptosis via ERK/JNK and Akt signaling pathway in human endometrial cancer

BackgroundPrevious studies have shown a major green tea polyphenol (−)-epigallocatechin-3-gallate ((−)-EGCG) as a powerful anti-cancer agent. However, its poor bioavailability and requirement of a high dosage to manifest activity have restricted its clinical application. Recently, our team synthesized a peracetate-protected derivative of EGCG, which can act as a prodrug of (−)-EGCG (ProEGCG) with enhanced stability and improved bioavailability in vitro and in vivo. Herein, we tested the therapeutic efficacy of this novel ProEGCG, in comparison to EGCG, toward human endometrial cancer (EC).MethodsIn this study, the effects of ProEGCG and EGCG treatments on cell growth, cell survival and modulation of intracellular signaling pathways in RL95–2 and AN3 CA EC cells were compared. The antiproliferative effect was evaluated by cell viability assay. Apoptosis was measured by annexin/propidium iodide staining. Expression of mitogen-activated protein kinases, markers of proliferation and apoptosis were measured by immunoblot analysis. In addition, the effects of ProEGCG and EGCG on tumor growth, vessel formation and gene expression profiles on xenograft models of the EC cells were investigated.ResultsWe found that treatment with ProEGCG, but not EGCG, inhibited, in a time- and dose-dependent manner, the proliferation and increased apoptosis of EC cells. Treatment with low-dose ProEGCG significantly enhanced phosphorylation of JNK and p38 MAPK and inhibited phosphorylation of Akt and ERK which are critical mediators of apoptosis. ProEGCG, but not EGCG, elicited a significant decrease in the growth of the EC xenografts, promoted apoptotic activity of tumour cells in the EC xenografts, and decreased microvessel formation, by differentially suppressing anti-apoptotic molecules, NOD1 and NAIP. Notably, no obvious adverse effects were detected.ConclusionsTaken together, ProEGCG at a low dose exhibited anticancer activity in EC cells through its anti-proliferative, pro-apoptotic and anti-tumor actions on endometrial cancer in vitro and in vivo. In contrast, a low dose of EGCG did not bring about similar effects. Importantly, our data demonstrated the efficacy and safety of ProEGCG which manifests the potential of a novel anticancer agent for the management of endometrial cancer.

Oncologic and pregnancy outcomes with fertility-sparing management for early-stage endometrial cancer in young women

Objective: The aim of this study is to evaluate the long-term oncologic and pregnancy outcomes of progestin treatment in young women with early-stage endometrial cancer who wish to preserve their fertility.