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Endometrial Cancer: Latest Advances and Prospects
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Endometrial Cancer: Latest Advances and Prospects

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: closed (20 June 2021) | Viewed by 18473

Special Issue Editor

Prof. Andrea Papadia

E-Mail Website
Guest Editor
Department of Obstetrics and Gynecology, Ospedale Regionale di Lugano, Ente Ospedaliero Cantonale, Faculty of Biomedical Sciences, Universita’della Svizzera Italiana, Lugano, Switzerland
Interests: gynecologic oncology; minimally invasive surgery; fluorescence-guided surgery; sentinel lymph node mapping; endometrial cancer; cervical cancer; ovarian cancer

Special Issue Information

Dear Colleagues,

Endometrial cancer is the most common gynecological malignancy in developed countries. Furthermore, its incidence and mortality are increasing. In the past few years, multiple lines of research have been developed. These range from the proposal of a new TCGA-based molecular classification system, to the adoption of the sentinel lymph node mapping for surgical staging as opposed to a full lymphadenectomy, to the adoption of fluorescent dyes for the sentinel lymph node mapping, and to the definition of new adjuvant treatment strategies tailored topathological findings (e.g. combined chemo-radiotherapy). All of these developments aim to create an improvement in oncologic outcomes and a reduction in treatment-related toxicities.
The present Special Issue aims to focus on recent advances in the management of endometrial cancer patients. In summary, treatment of endometrial cancer is constantly evolving and the development of new surgical techniques, new equpiments, as well as a new understanding of biological aspects has significantly impacted on the management of this malignancy.

Prof. Andrea Papadia
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Endometrial cancer
  • Minimally invasive surgery
  • Laparoscopy
  • Surgical staging
  • Sentinel lymph node mapping
  • Indocyanine green
  • Ultrastaging
  • Molecular classification
  • Adjuvant therapy
  • Radiotherapy
  • Chemotherapy

Published Papers (5 papers)

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Research

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12 pages, 1785 KiB  
Article
Medroxyprogesterone Reverses Tolerable Dose Metformin-Induced Inhibition of Invasion via Matrix Metallopeptidase-9 and Transforming Growth Factor-β1 in KLE Endometrial Cancer Cells
by Dong Hoon Suh, Sunray Lee, Hyun-Sook Park and Noh Hyun Park
J. Clin. Med. 2020, 9(11), 3585; https://doi.org/10.3390/jcm9113585 - 06 Nov 2020
Cited by 4 | Viewed by 2084
Abstract
This study was performed to evaluate the anticancer effects of tolerable doses of metformin with or without medroxyprogesterone (MPA) in endometrial cancer cells. Cell viability, cell invasion, and levels of matrix metallopeptidase (MMP) and transforming growth factor (TGF)-β1 were analyzed using three human [...] Read more.
This study was performed to evaluate the anticancer effects of tolerable doses of metformin with or without medroxyprogesterone (MPA) in endometrial cancer cells. Cell viability, cell invasion, and levels of matrix metallopeptidase (MMP) and transforming growth factor (TGF)-β1 were analyzed using three human endometrial adenocarcinoma cell lines (Ishikawa, KLE, and uterine serous papillary cancer (USPC)) after treatment with different dose combinations of MPA and metformin. Combining metformin (0, 100, 1000 µM) and 10 µM MPA induced significantly decreased cell viability in a time- and dose-dependent manner in Ishikawa cells, but not in KLE and USPC cells. In KLE cells, metformin treatment alone significantly inhibited cell invasion in a dose-dependent manner. The inhibitory effect of metformin was reversed when 10 µM MPA was combined, which was significantly inhibited again after treatment of MMP-2/9 inhibitor and/or TGF-β inhibitor. Changes of MMP-9 and TGF-β1 according to combinations of MPA and metformin were similar to those of invasion in KLE cells. In conclusion, the anticancer effects of tolerable doses of metformin varied according to cell type and combinations with MPA. Anti-invasive effect of metformin in KLE cells was completely reversed by the addition of MPA; this might be associated with MMP-9 and TGF-β1. Full article
(This article belongs to the Special Issue Endometrial Cancer: Latest Advances and Prospects)
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10 pages, 919 KiB  
Article
Low-Volume Nodal Metastasis in Endometrial Cancer: Risk Factors and Prognostic Significance
by Virginia García Pineda, Alicia Hernández Gutiérrez, Myriam Gracia Segovia, Jaime Siegrist Ridruejo, María Dolores Diestro Tejeda and Ignacio Zapardiel
J. Clin. Med. 2020, 9(6), 1999; https://doi.org/10.3390/jcm9061999 - 25 Jun 2020
Cited by 17 | Viewed by 2543
Abstract
Objective: To evaluate the oncological outcomes of patients with low-volume metastasis compared to those with macrometastasis and negative nodes in endometrial cancer. Methods: A single institutional retrospective study was carried out, which included all patients with endometrial cancer who underwent surgical treatment between [...] Read more.
Objective: To evaluate the oncological outcomes of patients with low-volume metastasis compared to those with macrometastasis and negative nodes in endometrial cancer. Methods: A single institutional retrospective study was carried out, which included all patients with endometrial cancer who underwent surgical treatment between January 2007 and December 2016. We analyzed the progression-free survival (PFS) and overall survival (OS) of all patients after sentinel node biopsy and full nodal surgical staging according to their final pathological nodal status, focusing on the impact of the size of nodal metastasis. Results: A total of 270 patients were operated on during the study period; among them, 230 (85.2%) patients underwent nodal staging. On final pathology, 196 (85.2%) patients had negative lymph nodes; low-volume metastasis (LVM) was present in 14 (6.1%) patients: 6 (2.6%) patients had isolated tumor cells (ITCs) and 8 (3.5%) patients presented just micrometastasis; additionally, 20 (8.7%) patients presented macrometastasis. After a median (range) follow-up of 60 (0–146) months, patients with macrometastasis showed a significantly worse PFS compared to LVM and node-negative patients (61.1% vs. 71.4% vs. 83.2%, respectively; p = 0.018), and similar results were obtained for 5-year OS (50% vs. 78.6% vs. 81.5%, respectively; p < 0.001). Half of the patients presenting LVM did not receive adjuvant treatment. Moreover, LVM had a moderate nonsignificant decrease in 5-year PFS compared to node-negative patients. Conclusions: Patients with endometrial cancer and low-volume nodal metastasis demonstrated a better prognosis than those presenting macrometastasis. Low-volume metastasis did not show worse oncological outcomes than node-negative patients, although there was a slight decrease in progression-free survival. Full article
(This article belongs to the Special Issue Endometrial Cancer: Latest Advances and Prospects)
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13 pages, 1040 KiB  
Article
Analysis of Systemic Inflammatory Factors and Survival Outcomes in Endometrial Cancer Patients Staged I-III FIGO and Treated with Postoperative External Radiotherapy
by Katarzyna Holub, Fabio Busato, Sebastien Gouy, Roger Sun, Patricia Pautier, Catherine Genestie, Philippe Morice, Alexandra Leary, Eric Deutsch, Christine Haie-Meder, Albert Biete and Cyrus Chargari
J. Clin. Med. 2020, 9(5), 1441; https://doi.org/10.3390/jcm9051441 - 12 May 2020
Cited by 16 | Viewed by 2448
Abstract
Background: The causal link between elevated systemic inflammation biomarkers and poor survival has been demonstrated in cancer patients. However, the evidence for this correlation in endometrial cancer (EC) is too weak to influence current criteria of risk assessment. Here, we examined the role [...] Read more.
Background: The causal link between elevated systemic inflammation biomarkers and poor survival has been demonstrated in cancer patients. However, the evidence for this correlation in endometrial cancer (EC) is too weak to influence current criteria of risk assessment. Here, we examined the role of inflammatory indicators as a tool to identify EC patients at higher risk of death in a retrospective observational study. Methods: A total of 155 patients surgically diagnosed with EC stage I-III FIGO 2009 and treated with postoperative External Beam Radiotherapy (EBRT) ± brachytherapy and chemotherapy according to ESMO-ESTRO-ESGO recommendation for patients at high risk of recurrence at the Gustave Roussy Institut, France, and Hospital Clínic, Spain, between 2008 and 2017 were evaluated. The impact of pre-treatment Neutrophil-to-Lymphocyte Ratio (NLR ≥ 2.2), Monocyte-to-Lymphocyte Ratio (MLR ≥ 0.18), Systemic Immune-Inflammatory Index (SII ≥ 1100) and lymphopenia (<1.0×109/L) on overall survival (OS), cancer-specific survival and progression-free survival was evaluated. Subsequently, a cohort of 142 patients within high-advanced risk groups according to ESMO-ESGO-ESTRO classification was evaluated. Results: On univariate analysis, NLR (HR = 2.2, IC 95% 1.1–4.7), SII (HR = 2.2, IC 95% 1.1–4.6), MLR (HR = 5.0, IC 95% 1.1–20.8) and lymphopenia (HR = 3.8, IC 95% 1.6–9.0) were associated with decreased OS. On multivariate analysis, NLR, MLR, SII and lymphopenia proved to be independent unfavorable prognostic factors. Conclusions: lymphopenia and lymphocytes-related ratio are associated with poorer outcome in surgically staged I-III FIGO EC patients classified as high risk and treated with adjuvant EBRT and could be considered at cancer diagnosis. External validation in an independent cohort is required before implementation for patients’ stratification. Full article
(This article belongs to the Special Issue Endometrial Cancer: Latest Advances and Prospects)
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Review

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13 pages, 1862 KiB  
Review
Endometrial Carcinomas with Intestinal-Type Metaplasia/Differentiation: Does Mismatch Repair System Defects Matter? Case Report and Systematic Review of the Literature
by Laura Ardighieri, Andrea Palicelli, Federico Ferrari, Mattia Bugatti, Emma Drera, Enrico Sartori and Franco Odicino
J. Clin. Med. 2020, 9(8), 2552; https://doi.org/10.3390/jcm9082552 - 06 Aug 2020
Cited by 24 | Viewed by 4269
Abstract
Background: Intestinal metaplasia/differentiation in primary endometrial carcinomas is an uncommon phenomenon, with only few cases described. Material and Methods: We performed a systematic review of endometrial carcinomas with intestinal metaplasia/differentiation interrogating the electronic databases Pubmed, Web of Science, and Scopus, and we reported [...] Read more.
Background: Intestinal metaplasia/differentiation in primary endometrial carcinomas is an uncommon phenomenon, with only few cases described. Material and Methods: We performed a systematic review of endometrial carcinomas with intestinal metaplasia/differentiation interrogating the electronic databases Pubmed, Web of Science, and Scopus, and we reported an additional case arising in a 49-year-old woman. Results: We identified only eight patients diagnosed with endometrial carcinomas exhibiting intestinal metaplasia/differentiation, and additionally our case. Endometrial carcinomas with intestinal-type features can present in pure or mixed forms in association with usual-type endometrioid carcinomas; in mixed forms, the two neoplastic components may derive from a common neoplastic progenitor, as evidenced by the concomitant loss of MSH2 and MSH6 protein expression in our case. Disease recurrences occur in a significant fraction of the cases, including patients diagnosed in low-stage disease. Conclusions: Endometrial carcinomas with intestinal metaplasia/differentiation are rare and they may represent a more aggressive tumor variant, thus requiring a proper treatment despite the low-tumor stage. The ProMise classification should be performed also in these unusual tumors, since they can be associated with mismatch repair system defects. Full article
(This article belongs to the Special Issue Endometrial Cancer: Latest Advances and Prospects)
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15 pages, 279 KiB  
Review
Immune Checkpoint Inhibitors: A Promising Choice for Endometrial Cancer Patients?
by Lucia Musacchio, Serena Maria Boccia, Giuseppe Caruso, Giusi Santangelo, Margherita Fischetti, Federica Tomao, Giorgia Perniola, Innocenza Palaia, Ludovico Muzii, Sandro Pignata, Pierluigi Benedetti Panici and Violante Di Donato
J. Clin. Med. 2020, 9(6), 1721; https://doi.org/10.3390/jcm9061721 - 03 Jun 2020
Cited by 41 | Viewed by 6407
Abstract
Although around 80% of endometrial cancers are diagnosed at early stages and present with a 5-year survival rate exceeding 95%, patients with advanced and recurrent disease show a poor prognosis and low response rates to standard chemotherapy. In the era of targeted therapy, [...] Read more.
Although around 80% of endometrial cancers are diagnosed at early stages and present with a 5-year survival rate exceeding 95%, patients with advanced and recurrent disease show a poor prognosis and low response rates to standard chemotherapy. In the era of targeted therapy, the great advances in the understanding of programmed death-ligand 1 (PD-L1) upregulation in cancer cells, which is responsible for tumor immune escape, have contributed to the increasing interest in immune checkpoint inhibitors as a promising strategy for the treatment of several refractory solid malignancies, including endometrial cancer. Several clinical trials have investigated the efficacy and safety of immune checkpoint inhibitors in endometrial cancer, which already led to the approval of the anti-programmed cell death protein 1 (anti-PD-1) antibody pembrolizumab as a satisfactory alternative for selected patients with unresectable or metastatic disease. As the future of cancer treatment will probably rely on combination therapy strategies, currently, innovative ongoing trials are exploring the potential role of immune checkpoint inhibitors associated with chemotherapy, radiotherapy, and other targeted therapies. Moreover, further research is warranted to discover new specific biomarkers that can accurately predict the response to immunotherapy. Full article
(This article belongs to the Special Issue Endometrial Cancer: Latest Advances and Prospects)
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