Search Results (102)

Background: Endometrial cancer (EC) is the most common gynecological malignancy, increasingly affecting premenopausal women. While hysterectomy is the standard treatment, it eliminates reproductive potential, highlighting the need for effective fertility-sparing alternatives. Current ESHRE/ESGO/ESGE guidelines recommend progestin-based therapies, often with hysteroscopic resection. However, these are based on limited pharmacological options and moderate to low-quality evidence. Novel and combination therapies have shown promise but remain absent from current clinical guidelines. This review aims to evaluate the efficacy and safety of fertility-preserving treatments for early-stage EC, emphasizing the need to update current strategies based on emerging data. Methods: A systematic review and meta-analysis will follow PRISMA guidelines and the Cochrane Handbook. Eligible studies, including randomized and non-randomized designs, will assess fertility-preserving treatments for early-stage EC. Data will be extracted on complete response, recurrence, and long-term fertility outcomes. The GRADE system will assess evidence certainty. Risk of bias will be evaluated using RoB 2 for RCTs and ROBINS-I for non-randomized studies. Meta-analysis will be performed if sufficient data are available. Conclusions: This review will provide a comprehensive analysis of fertility-sparing treatments for early-stage EC, support personalized strategies, identify evidence gaps, and guide future research. Trial registration—Prospero: CRD420251032161. Full article

Background: Following the results of the Laparoscopic Approach to Carcinoma of the Cervix (LACC) trial, doubts have arisen about the safety of laparoscopy in the treatment of endometrial cancer. Methods: A retrospective multicenter cohort study which included all endometrial cancer (EC) patients who underwent a hysterectomy in Emilia Romagna hospitals from 2000 to 2019. All cases were revised and classified according to the 2009 International Federation of Gynaecology and Obstetrics (FIGO) staging system. The different impacts of the surgical approach on survival were stratified according to the recurrence risk from the 2016 European Society for Medical Oncology (ESMO)–European Society of Gynaecological Oncology (ESGO) classification system. The clinical characteristics and oncological outcome of patients treated by laparoscopy were compared with those treated by laparotomy. Results: A total of 2402 EC patients were included in the study. The use of laparoscopy has increased over the years, reaching 81% of procedures in 2019. Laparoscopy reduced complications and hospital stay. Laparoscopy was preferred to treat low, intermediate, and intermediate/high-risk patients. Laparoscopy showed no adverse effects on overall survival (OS) in any recurrence risk class. Particularly in high-risk EC patients, laparoscopy was associated with an increased OS in comparison with women treated by laparotomy regardless of the use of adjuvant therapy. Conclusions: Laparoscopy should always be chosen to treat EC of any risk class. The goal is to ensure correct treatment and oncological safety regardless of the surgical approach. Full article

Background and Objectives: The aim of this prospective study was to evaluate the diagnostic accuracy of the one-step nucleic acid amplification (OSNA) assay for the intraoperative assessment of sentinel lymph node (SN) metastases, including micrometastases in patients with stage IA low-grade endometrial cancer. Materials and Methods: A prospective analysis was conducted on 204 patients with low-risk endometrial cancer who underwent hysterectomy, bilateral salpingo-oophorectomy, and sentinel node navigation surgery. SNs were analyzed intraoperatively using the OSNA assay, and positive patients underwent systematic pelvic lymphadenectomy. Results: Among the 204 patients included, SN metastases were identified in 12 patients (6%), including 10 patients with micrometastases and 2 patients with macrometastases. No metastases were detected in non-SNs in any of the 12 patients. Recurrence occurred in two patients (1%), involving the vaginal stump and pelvic cavity dissemination, but no lymph node recurrence was observed. The OSNA assay identified a proportion of micrometastases in low-risk endometrial cancer. While a direct comparison with conventional pathological ultra-staging was not performed in this study, the detection rate of micrometastases appears higher than that reported in historical controls. Conclusions: This is the first prospective study to evaluate the intraoperative use of the OSNA assay for whole SNs in endometrial cancer. The results suggest that the OSNA assay enhances the detection of micrometastases, enabling a more accurate assessment of SN metastases. In low-risk endometrial cancer, systematic pelvic lymphadenectomy may be safely omitted in patients with SN-positive micrometastases. Further prospective studies are necessary to validate these findings and support the adoption of this approach in clinical practice. Full article

Background: Endometrial cancer is among the most prevalent gynecological malignancies, with increasing mortality primarily due to initially advanced disease with lymph node metastasis or tumor recurrence. Current risk stratification models show limited accuracy, highlighting the need for more accurate biomarkers. This study aimed to identify metabolic compounds that can serve as predictors of recurrence risk and lymph node status in endometrial cancer. Methods: Targeted metabolomic profiling of preoperative serum samples from 123 patients with endometrial cancer, stratified into high- or low-risk and lymph node-positive or -negative groups, was conducted using the AbsoluteIDQ p180 Kit and high-performance liquid chromatography–mass spectrometry. Results: Analysis revealed significant differences in metabolites related to lipid and amino acid metabolism between groups. High-risk and lymph node-positive patients presented significantly lower concentrations of phosphatidylcholines, lysophosphatidylcholines, medium-chain acylcarnitines, and specific amino acids such as alanine, histidine, and tryptophan compared to low-risk and lymph node-negative patients. Receiver operating characteristic curve analyses highlighted the diagnostic potential of these metabolites, particularly alanine and taurine, in distinguishing patient groups. Conclusions: The findings indicate complex metabolic reprogramming associated with aggressive endometrial cancer phenotypes, involving enhanced lipid utilization and amino acid metabolism alterations, potentially supporting tumor proliferation and metastatic progression. Thus, targeted metabolomic serum profiling might be a powerful tool for improving risk assessment, enabling more personalized therapeutic approaches and management strategies in endometrial cancer. Full article

Background/Objectives: Endometrial cancer (EC) is the most common malignancy of the female genital tract. In 2013, The Cancer Genome Atlas analyzed the molecular profile of endometrial tumors identifying four risk classes (POLE ultramutated, mismatch repair-deficient, copy-number low-microsatellite stable, and copy-number high-serous-like. This classification is reshaping the current understanding of EC, enabling more refined risk stratification and uncovering potential therapeutic targets tailored to specific molecular subgroups. In the context of these four categories, it is possible to identify different molecular alterations that correlate with different prognoses. Methods and Results: We retrospectively analyzed tissue samples from eighty-five EC patients, performing multigene profiling using a 50-gene next-generation sequencing (NGS) panel to categorize them into distinct molecular subtypes; we observed the following distribution: 5.9% POLE, 25.8% mismatch repair-deficient/microsatellite instability (MMRd/MSI), 11.8% p53abn/TP53mut, and 56.5% NSMP. A favorable concordance (97.6%) was shown in MSI NGS-based analysis and MMR IHC results, and the agreement rate of p53 IHC and TP53 mutation was 92.3%. When we analyzed the correlation between molecular subtypes and clinicopathological features, we found that molecular subtypes significantly differentiated by grade, FIGO stage, and lymphovascular invasion (LVSI). These findings seem to support the effectiveness of our NGS-based classifier and its reliability in distinguishing both MSI and TP53 mutated cancers. This study also explored mutations in PIK3CA, PTEN, KRAS, ERBB2, and ESR1 genes, noting their potential as targets for treatments. PIK3CA mutations were linked to favorable features, such as early disease stage and absence of LVSI. Conclusions: Our study highlights the potential of a medium-complexity NGS panel for supporting the molecular classification of endometrial cancer, complementing the existing diagnostic algorithms. By identifying additional biomarkers, we provided valuable insights into the genomic landscape of EC. However, further exploration of the molecular profiles is needed to validate these findings and improve the identification of patients at a higher risk of unfavorable outcomes. Full article

Introduction: Endometrial cancer is the most common malignancy of the female genital tract in high-income countries. A prompt diagnosis of this condition is of utmost importance in ensuring that patients receive the best treatment strategy. The new FIGO 2023 molecular classification of endometrial cancer radically changes the current landscape of this disease’s treatment and follow-up. Among the various diagnostic techniques used to identify endometrial lesions, hysteroscopy and vacuum biopsy techniques are the most employed in clinical practice. The aim of this systematic literature review is to compare the efficacy, sensitivity, specificity, and safety of these methods when employed to diagnose endometrial cancer, as well as to assess the feasibility of endometrial cancer molecular profiling on biopsy specimens. Methods: A systematic literature search of studies evaluating hysteroscopy and VABRA biopsy performance in diagnosing endometrial cancer was conducted using the main online databases (PubMed, EMBase, Cochrane Library). An additional literature search was conducted, focusing on the feasibility of endometrial cancer molecular profiling on hysteroscopic biopsy and VABRA samples, as well as on the diagnostic concordance of biopsy and final surgery specimens. Two authors performed the literature search independently, while other two authors assessed the retrieved publications’ risk of bias using Begg’s and Egger’s tests. Twenty-four studies were included in the final report. Results: Both techniques have shown high effectiveness in diagnosing endometrial cancer, although with important differences. Hysteroscopy provides direct visualization of the endometrium and allows clinicians to perform biopsies of suspicious lesions, but it also entails important limitations, as in the case of diffused lesions or technical difficulties, especially in nulliparous and elderly women. VABRA and other vacuum biopsy techniques, on the other hand, offer a wider sampling of endometrial tissue and are less operator-dependent but may be associated with a higher risk of failed diagnosis when compared to hysteroscopy. Discussion: Hysteroscopy, especially when combined with targeted biopsies, has been proven to be a valid technique, especially in pre-surgical diagnostic workup of early-stage endometrial cancer. Vacuum techniques, although less invasive and providing larger tissue samples, do not seem to be able to completely replace hysteroscopy in diagnosing endometrial cancer but remain a valid alternative in selected cases, especially when endometrial lesions prove harder to reach and/or to identify. They may also prove useful in low resource countries in which hysteroscopy is not widely available. Conclusions: Based on our findings, early assessment of endometrial cancer should be carried out through hysteroscopic evaluation and targeted endometrial biopsies, ideally including molecular assessment on biopsy specimens to further guide treatment decisions. Other biopsy techniques, such as vacuum-assisted biopsy, should be reserved for specific settings in which hysteroscopy is not readily available. The ideal diagnostic approach to endometrial cancer should take multiple factors into account, such as the location and extension of the disease, patient characteristics, clinical skills, and resource availability. Further studies are needed to assess the feasibility of molecular cancer profiling on biopsy specimens, as well as cost-containment strategies which would allow equal access to targeted treatment modalities for all endometrial cancer patients worldwide. Full article

Background/Objectives: Endometrial hyperplasia is a uterine pathology characterized by the abnormal proliferation of endometrial glands, resulting in an increased gland-to-stroma ratio. Complex atypical hyperplasia represents the primary precursor to endometrial cancer. Given the high risk of progression to endometrial adenocarcinoma, the accurate diagnosis and classification of endometrial hyperplasia are crucial. Since the treatment for atypical endometrial hyperplasia is the same as that for early-stage endometrial cancer (i.e., total hysterectomy and bilateral salpingo-oophorectomy), researchers have questioned whether sentinel lymph node mapping could also have a prognostic role in atypical endometrial hyperplasia. Methods: A literature search was conducted in PubMed and Scopus from 2014 to 2025. Of the 65 papers found, 31 relevant articles were selected based on inclusion criteria, focusing on sentinel lymph node staging in patients with atypical endometrial hyperplasia. This review aims to assess whether sentinel lymph node mapping can be routinely used for prognostic and therapeutic purposes in clinical practice. Results: Sentinel lymph node biopsy represents a promising diagnostic technique for patients with atypical endometrial hyperplasia, reducing the need for invasive procedures and postoperative risks. However, its application requires advanced surgical skills and access to specific technologies, raising ethical and financial concerns, while future studies could improve patient selection and the reliability of the procedure through technological innovations. Conclusions: Sentinel lymph node biopsy is a safe and effective method for staging early-stage endometrial cancer and atypical hyperplasia, with low metastasis rates, but future research should focus on identifying patients who would benefit most from this procedure, considering its costs and required expertise. Full article

Endometrial cancer (EC) is an immunogenic tumor, with CD8⁺ T cells playing a pivotal role in antitumor immunity. Overexpression of PD1 suppresses T cell function by inhibiting CD28, a critical co-stimulatory molecule. Classifying CD8⁺ T cells based on PD1 and CD28 expression provides valuable insights into the immune microenvironment of EC. Peripheral blood samples from 120 EC patients and tumor tissue samples from 81 EC patients were analyzed via flow cytometry. CD8⁺ T cells were categorized according to PD1 and CD28 expression, and their associations with clinical characteristics were systematically evaluated. Peripheral CD28⁻/CD8⁺ and PD1⁺/CD8⁺ T cell proportions were significantly associated with several high-risk factors, including deep myometrial invasion, and LVSI, as well as metabolic disorders such as dyslipidemia. Peripheral CD28⁺PD1⁻/CD8⁺ T cells were associated with stage, grade, and LVSI, inversely correlated with age, and elevated in patients with hypertension or dyslipidemia. Tumor-infiltrating CD28⁺PD1⁻/CD8⁺ T cells were associated with tumor grade and LVSI, with multivariate analysis identifying low proportions as an independent predictor of relapse. In summary, CD8⁺CD28⁻ and CD8⁺PD1⁺ T cells are linked to high-risk clinical features in EC, while tumor-infiltrating CD8⁺CD28⁺PD1⁻ T cells serve as a key independent prognostic marker for relapse. Additionally, CD8⁺CD28⁻, CD8⁺PD1⁺, and CD8⁺CD28⁺PD1⁻ T cell proportions in PBMC are closely associated with metabolic disorders, emphasizing their potential as biomarkers for immune and metabolic interactions in EC. Full article

Objective: Obesity is a major risk factor for endometrial cancer. In addition to hormone therapy with progestins, glucagon like peptide-1 receptor (GLP-1R) agonists such as semaglutide may be helpful to achieve weight loss during conservative treatment of endometrial hyperplasia or cancer. Methods: We theorized that the combination of semaglutide and the progestin levonorgestrel would be useful as a novel treatment or prevention regimen and tested this hypothesis using endometrial cancer cell lines and patient-derived organoids (PDOs). Results: Hec50, KLE, and Ishikawa endometrial cancer cells express GLP-1R, as determined by both qPCR and Western blotting, and GLP-1R agonist treatment induces GLP-1R mRNA transcription through positive feedback mechanisms in cell models. PDOs from six individuals with grade 1 endometrial carcinomas were treated with progesterone, levonorgestrel, semaglutide, or levonorgestrel + semaglutide. Multiple models demonstrated a significant reduction in viability in response to combinatorial treatment, and the effect was noted in models from both PR high- and PR low-expressing tumors. Most interesting was the induction not only of the membrane GLP-1R with treatment, but also the significant upregulation of nuclear and membrane progesterone receptors—PR and PGRMC1/2, respectively—indicating a potential positive feedback loop between semaglutide and progestins such as levonorgestrel. Conclusion: In summary, we identify synergistic molecular cross-talk between the GLP-1R and steroid hormone receptor pathways, with the potential to enhance the anticancer activity of levonorgestrel when combined with semaglutide. Full article

Patients with endometrial neoplasia (EN) often have multiple comorbidities and a higher surgical risk. Prehabilitation programs (PPs) combine various interventions to improve preoperative conditions and reduce impairment due to surgical stress. We conducted a pragmatic pilot study to evaluate the acceptability and feasibility of a trimodal telehealth PP (exercise, nutrition, and psychological support) for EN patients. The participants could select their exercise group: (1) a supervised PP (SPP), group sessions 3×/week; (2) a semi-supervised PP (SSPP), group session 1×/week, training alone 2×/week; or (3) a physical activity counseling session (PACS). Out of the 150 EN patients awaiting surgery screened during the 18 months of the study recruitment, 66% (99/150) were eligible, and 40% consented to participate (SPP, n = 13; SSPP, n = 17; PACS, n = 9). The overall dropout was low (13%; 5/39), with no significant differences across groups. No serious adverse events occurred. We observed a positive impact on different outcomes across the different groups, such as in the Functional Assessment of Cancer Therapy quality of life score (SPP; delta = 6.1 [CI: 0.9; 12.6]) and functional capacity measured using the 30″ sit-to-stand test (PACS delta = 2.4 [CI: 1.2; 3.6]). The same-day hospital leave was high in the SSPP group (54.5%). Our pilot telehealth PP seems to be safe, feasible, and well accepted and may procure clinical and patient-centered gains that need to be confirmed in a larger trial. Full article

In today’s world, with its continuing advancements in genetics, the identification of Lynch syndrome (LS) increasingly relies on sophisticated genetic testing techniques. Most guidelines recommend a tailored surveillance program, as well as personalized prophylactic and therapeutic approaches, according to the type of dMMR gene mutation. Carriers of path_MLH1 and path_MSH2 genes have a higher risk of developing colorectal cancer (CRC), despite intensive colonoscopic surveillance. Conversely, carriers of path_MSH6 and path_PMS2 genes have a lower risk of developing CRC, which may be due to their lower penetrance and later age of onset. Thus, carriers of path_MLH1 or path_MSH2 would theoretically derive greater benefits from total colectomy, compared to low-risk carriers (path_MSH6 and path_PMS2), in which colonoscopic surveillance might achieve an efficient prophylaxis. Furthermore, regarding the risk of endometrial/ovarian cancer development, there is a global agreement to offer both hysterectomy and bilateral salpingo-oophorectomy to path_MLH1, path_MSH2 and path_MSH6 carriers after the age of 40. In patients with CRC, preoperative knowledge of the diagnosis of LS is of tremendous importance, due to the high risk of metachronous CRC. However, this risk depends on the type of dMMR gene mutation. For carriers of the high-risk variants (MLH1, MSH2 and EPCAM) who have already developed colon cancer, it is strongly recommended a subtotal or total colectomy is performed, while partial colectomy followed by endoscopic surveillance is an appropriate management approach to treat colon cancer in carriers of the low-risk variants (MSH6 and PMS2). On the other hand, extended surgery for index rectal cancer (such as total proctocolectomy) is less effective than extended surgery for index colon cancer from the point of view of metachronous CRC risk reduction, and is associated with a decreased quality of life. Full article

This review evaluates the advances in the early detection and diagnosis of endometrial cancer (EC), emphasizing the growing importance of minimally invasive techniques and novel biomarkers. Current diagnostic protocols for EC rely heavily on invasive procedures such as transvaginal ultrasound (TVU), hysteroscopy, and endometrial biopsy, which, although effective, can be overly burdensome for patients and inefficient for asymptomatic or low-risk populations. As there is no consensus on EC screening in high-risk or general populations, recent studies have explored alternative methods using biofluids and genomic biomarkers to improve sensitivity and specificity and facilitate access for patients. This review summarizes findings on DNA methylation markers, circulating tumor-derived nucleic acids, and the potential of liquid biopsy approaches for the early detection of EC. These innovations may not only streamline screening but also reduce the need for invasive procedures. This review highlights the potential of these biomarkers to be integrated seamlessly into the existing cervical cancer screening programs, which could transform screening methods for endometrial cancer and support the development of personalized, less invasive diagnostic procedures. Full article

Background and Objectives: This study aims to evaluate and compare the safety and efficacy of the da Vinci^® Xi and hinotori™ SRS robot-assisted surgical systems for gynecologic disorders. Materials and Methods: We conducted a retrospective study of 401 cases (43 benign uterine tumors; 88 pelvic organ prolapses; 270 low-risk endometrial cancers) of robot-assisted surgery performed at Kagoshima University Hospital between January 2017 and October 2024. Surgical factors such as the operative time, blood loss, and complication rates were analyzed and compared between the da Vinci^® Xi (332 cases) and hinotori™ SRS (69 cases) systems. Complications were classified according to the Clavien–Dindo classification, with Grade 2 or higher considered significant. Results: Significant differences were observed between the two groups in terms of age, body mass index, cockpit/console time, and median time from roll-in to cockpit/console start. The cockpit/console time was significantly longer for the hinotori™ SRS system (173 min) compared to the da Vinci^® Xi (156 min; p = 0.047). No significant differences were observed in the total operative time, blood loss, or length of hospital stay. Intraoperative complications were minimal, with one case of bladder injury and one case of vascular injury recorded for the da Vinci^® Xi. The overall postoperative complication rate was approximately 4%. Conclusions: Robot-assisted surgery using both the da Vinci^® Xi and hinotori™ SRS systems was found to be safe, with minimal blood loss and a low complication rate. The hinotori™ SRS system demonstrated operative outcomes comparable to those of the da Vinci Xi^® system, suggesting that it may serve as a viable alternative. Further prospective studies are warranted to evaluate the efficacy and safety of these systems. Full article

Upper para-aortic lymph node dissection (PALND) is one of the most challenging gynecologic robotic procedures. This study aimed to evaluate the oncologic and operative outcomes of robotic staging surgery, including upper PALND, using low pelvic port placement (LP3) in 22 patients with high-risk endometrial cancer. High-risk was defined as patients who showed deep myometrial invasion with grade III, cervical involvement, or high-risk histology. The mean patient age and body mass index were 58 years and 24 kg/m². The mean operative time was 263 min. The mean number of total LNs and upper PALNs obtained was 31 and 10. Two patients received lymphangiography to reduce the amount of drained lymphatic fluid after surgery. The recurrence rate was 13.6% (3/22). There were two LN recurrences and one at the peritoneum in the intra-abdominal cavity. Robotic staging surgery using LP3 was feasible for performing PALND as well as procedures in the pelvic cavity simultaneously. It provides important techniques for performing optimal surgical procedures when surgeons decide to perform comprehensive PALND in instances of isolated recurrence or unexpected LN enlargement as well as high-risk endometrial cancer. Consequently, surgeons can achieve surgical consistency and reproducibility for PALND, leading to improved operative and survival outcomes in high-risk endometrial cancer. Full article

Background/Objectives: Radiotherapy represents the only treatment option for patients with inoperable endometrial cancer (EC). The aim of our study was to evaluate the efficacy and safety of brachytherapy (BT) in this selected patient population. Methods: Between 1990 and 2019, 18 patients with inoperable EC in stage FIGO I–IV were treated with intracavitary brachytherapy using the “Heyman Packing technique”. BT was performed either as sole PDR- or HDR-brachytherapy with a median cumulative dose up to 60.0 Gy (67.9 Gy _{EQD2 α/β = 3Gy}) and 34.0 Gy (75.6 Gy _{EQD2 α/β = 3Gy}), respectively. Results: The median follow-up was 46 months (6–219). The mean age was 71 years. The 5-year cumulative local recurrence rate (CLRR) for the whole cohort was 27.3%. The 5-year overall survival (OS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) were 51%, 79%, and 69%. The 5-year DFS for low-, intermediate-, and high-risk EC was 89%, 50%, and 44% (p = 0.51). No significant difference in DFS was observed in patients over 70 (p = 0.526). No late side effects of grade > 1 were documented. Conclusions: Brachytherapy for inoperable EC is a safe and effective treatment option, offering good local control and OS with minimal toxicity. Moreover, brachytherapy effectively controls hemoglobin-relevant bleeding. Therefore, BT should be considered a viable alternative to non-curative treatment strategies in gynecological multidisciplinary conferences. Full article