Search Results (231)

Background: The year 2025 witnessed paradigm-shifting advances in gynecologic oncology, with pivotal clinical trial results redefining therapeutic standards across cervical, ovarian, endometrial, and vulvar cancers. Objectives: This systematic review aimed to comprehensively identify, synthesize, and critically evaluate pivotal phase II and III randomized controlled trials and major studies presented at the major annual meetings, alongside significant peer-reviewed publications from 2025 that introduce innovative therapeutic strategies across gynecologic malignancies. Methods: Conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, this review involved exhaustive searches of electronic databases (PubMed/MEDLINE, Embase), conference proceedings (ASCO 2025, ESMO 2025), and major oncology journals for records from January to December 2025. Inclusion criteria encompassed: (1) Phase II or III randomized controlled trials (RCTs) and (2) Non-randomized studies (including phase I and II trials), reporting on novel therapeutic approaches in gynecologic oncology. All studies were required to report primary survival endpoints (overall survival or progression-free survival) or key efficacy outcomes. Study selection, data extraction, and methodological quality assessment were performed independently by two reviewers, with disagreements resolved through consensus or third-party adjudication. Results: From 1842 records, 23 studies met inclusion criteria (17 phase-III RCTs and 6 non-phase III RCTs/early-phase studies), distributed as follows: cervical cancer (9 studies, 39%), ovarian cancer (9 studies, 39%), endometrial cancer (4 studies, 17.5%), and vulvar cancer (1 study, 4.5%). The major advances identified include: (1) In cervical cancer, the KEYNOTE-A18 trial established pembrolizumab combined with chemoradiotherapy as a new standard for high-risk locally advanced disease, while the PHENIX trial validated sentinel lymph node biopsy as a safe surgical de-escalation strategy. (2) In ovarian cancer, the ENGOT-ov65/KEYNOTE-B96 trial demonstrated the first statistically significant overall survival improvement with an immune checkpoint inhibitor in platinum-resistant recurrent disease, establishing pembrolizumab plus weekly paclitaxel as a new standard of care. Novel therapeutic mechanisms, including glucocorticoid receptor modulation (ROSELLA trial) and cadherin-6-targeted antibody-drug conjugates (REJOICE-Ovarian01), showed remarkable efficacy. (3) In endometrial cancer, updated analyses from NRG GY018 and RUBY trials solidified the role of first-line immuno-chemotherapy, with differential benefits according to mismatch repair status. (4) In vulvar cancer, a pivotal phase II study demonstrated meaningful clinical activity of anti-PD-1 therapy in advanced disease. (5) The extensive circulating tumor DNA analysis from the CALLA trial provided crucial insights into biomarker dynamics in cervical cancer. Conclusions: The convergence of high-impact data from 2025 established multiple new standards of care, emphasizing biomarker-driven approaches, immunotherapy integration across disease stages, and novel mechanisms to overcome resistance, while highlighting challenges in treatment sequencing and global access. Full article

Background/Objectives: The combination of chemotherapy and radiotherapy represents a standard adjuvant treatment for patients with high-risk endometrial cancer. However, limited access to radiotherapy in many healthcare systems frequently results in treatment delays, potentially compromising outcomes. The aim of this study was to evaluate the oncologic outcomes and toxicity profile of an inverted treatment sequence consisting of upfront chemotherapy followed by concurrent chemoradiotherapy. Methods: We conducted a retrospective single-center study including patients with non-metastatic high-risk endometrial cancer. Eligible patients had FIGO stage I grade 3 disease with lymphovascular space invasion, stage II–III disease, or non-endometrioid histology. All patients received four cycles of paclitaxel–carboplatin followed by pelvic radiotherapy with concurrent cisplatin. Survival outcomes, including local recurrence-free survival, disease-free survival, metastasis-free survival, and overall survival, were analyzed using the Kaplan–Meier method and Cox proportional hazards models. Acute hematologic toxicity was graded according to CTCAE v5.0. Bone marrow dose–volume parameters were evaluated, and receiver operating characteristic curve analysis was performed to identify thresholds associated with grade ≥ 2 hematologic toxicity. Results: Fifty-two patients were included, with a median follow-up of 31.4 months. Five-year overall survival and disease-free survival rates were 86.1% and 77.5%, respectively. Ten patients relapsed, with distant metastases observed in all cases and synchronous local recurrence in one. Delays between surgery and radiotherapy of 20 weeks or more, as well as delays exceeding 10 weeks before initiation of chemotherapy, were associated with significantly reduced disease-free survival. Grade ≥ 2 hematologic toxicity was frequent, and neutropenia was associated with inferior overall survival. Bone marrow dose–volume thresholds predictive of hematologic toxicity included V40 Gy < 20–25% and V30 Gy < 40%. Conclusions: A chemotherapy-first adjuvant strategy provides favorable oncologic outcomes and excellent locoregional control in high-risk endometrial cancer when radiotherapy is delayed. However, increased hematologic toxicity highlights the importance of optimized bone marrow sparing. Full article

Endometrial cancer is the most common gynaecologic malignancy in high-income countries, with a rising incidence largely driven by reproductive factors, obesity, and prolonged exposure to unopposed oestrogens. Although most cases are sporadic, approximately 2–5% are associated with hereditary cancer syndromes, of which Lynch syndrome represents the most important contributor. Lynch syndrome results from germline mutations in DNA mismatch repair (MMR) genes and is associated with a substantially increased lifetime risk of endometrial cancer, reaching up to 71% in carriers of MutS homologue 6 (MSH6) mutations. Hereditary cancer predisposition typically follows an autosomal dominant inheritance pattern and may be suspected based on clinical warning signs such as early disease onset, multiple primary malignancies, a strong family history, or the presence of microsatellite instability in tumour tissue. In addition to Lynch syndrome, rarer genetic conditions—including Cowden syndrome (PTEN), Li–Fraumeni syndrome (TP53), polymerase proofreading–associated polyposis (POLE/POLD1), and hereditary breast and ovarian cancer syndromes (BRCA1/2)—also contribute to hereditary endometrial cancer risk. Recognition of these genetic backgrounds is essential for accurate diagnosis, personalised surveillance, and the implementation of targeted preventive and therapeutic strategies. Despite major advances in molecular diagnostics, hereditary endometrial cancer remains frequently underdiagnosed, leading to missed opportunities for cancer prevention among affected individuals and their families. This comprehensive review summarises current evidence on hereditary predispositions to endometrial cancer, with a particular emphasis on Lynch syndrome, and discusses underlying genetic mechanisms, inheritance patterns, diagnostic strategies, and clinical implications for screening, genetic counselling, and treatment optimisation. Full article

Background/Objectives: With the rising incidence of obesity-related endometrial cancer, there is renewed interest in physiologic, low-cost approaches to identify women with hormonally active endometrium who may benefit from early preventive interventions. The progesterone challenge test (PCT), an established clinical tool for evaluating amenorrhea, has been previously proposed as a method to detect endometrial pathology. This study systematically evaluated the diagnostic accuracy of the PCT for detecting endometrial hyperplasia, intraepithelial neoplasia, and carcinoma in asymptomatic postmenopausal women to determine its potential role as a physiologic marker of endometrial cancer risk. Methods: A systematic review and meta-analysis were conducted following PRISMA-DTA guidelines. MEDLINE, EMBASE, EBM Reviews, and CINAHL were searched from inception to 20 January 2025, along with ClinicalTrials.gov and grey literature. Eligible studies prospectively evaluated the PCT with endometrial biopsy as the reference standard. Data extraction and risk-of-bias assessment were performed in duplicate. Risk of bias was assessed using QUADAS-2. Pooled sensitivity, specificity, and predictive values were estimated using hierarchical summary receiver operating characteristic models. Results: Nineteen studies (n = 3902) met the inclusion criteria. The pooled sensitivity and specificity of the PCT for detecting endometrial pathology were 95% (95% CI 86–100%) and 87% (76–96%), respectively. The positive predictive value was 32% (95% CI, 16–50%) and the negative predictive value was 100% (100–100%). When endometrial proliferation was included in the target condition, sensitivity decreased to 82%, but positive predictive value increased to 70%. Conclusions: The PCT shows high diagnostic accuracy for identifying estrogen-driven endometrial pathology in asymptomatic postmenopausal women. Re-evaluating this simple, physiologic test as a functional risk-stratification tool could inform precision prevention strategies for endometrial cancer. Full article

Background: As a newly recognized type of cell death implicated in cancer, ferroptosis plays multiple roles in tumor biology. Here, we sought to construct a prognostic framework for EC on the basis of ferroptosis-related long non-coding RNAs (FerlncRNAs), microRNAs (FermiRNAs), and mRNAs (FRGs) for endometrial cancer (EC). Methods: Transcriptomic profiles of tumors and matched clinical data for 544 EC patients were retrieved from TCGA-UCEC. A prognostic framework was generated through Cox regression, integrating ferroptosis-linked lncRNAs, miRNAs, and mRNAs. EC cases were stratified into groups with high or low predicted risk based on ferroptosis-related gene expression. The model’s prognostic utility was examined through Kaplan–Meier (K–M) analysis and receiver operating characteristic curves. Results: A prognostic model based on 16 RNAs, including 10 FerlncRNAs, 2 FermiRNAs, and 4 FRGs, was developed. Analysis using K–M plots showed that high-risk patients experienced shorter overall survival than their low-risk counterparts (p < 0.001). The model’s area under curve (AUC) values were 0.731, 0.749, and 0.768 at 1-, 3-, and 5-year time points, surpassing those of standard clinical parameters. Furthermore, in an external validation cohort, these signature RNAs were associated with EC prognosis. Conclusions: The novel ferroptosis-related lncRNA–miRNA–mRNA prognostic model provides a basis to assess clinical prognosis in EC patients. Full article

Background and Objectives: Para-aortic lymph node involvement is a key prognostic factor in high-risk endometrial cancer. This study aimed to identify factors associated with para-aortic lymph node metastasis and to assess their predictive value for surgical decision-making. Materials and Methods: A retrospective analysis was conducted on 81 patients with high-risk endometrial cancer who underwent systematic pelvic and para-aortic lymphadenectomy between January 2015 and December 2024. Factors evaluated included histologic subtype, lymphovascular space invasion (LVSI), cervical stromal involvement, depth of myometrial invasion, and tumor diameter. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of para-aortic metastasis. Receiver operating characteristic (ROC) analysis was used to determine the optimal tumor size threshold. Results: Para-aortic lymph node metastasis was identified in 21.0% of patients, and isolated para-aortic metastasis was observed in 2.5%. In univariate analysis, pelvic lymph node positivity, LVSI, cervical stromal invasion, deep myometrial invasion, and tumor size ≥ 3.55 cm were significantly associated with para-aortic spread. Multivariate analysis revealed that pelvic lymph node positivity was the only independent predictor (OR 39.0; 95% CI 5.06–301.46; p < 0.001). Conclusions: Pelvic lymph node status serves as a strong and independent predictor of para-aortic metastasis in high-risk endometrial cancer. A tumor diameter greater than 3.5 cm may also indicate an increased risk of para-aortic spread. These findings suggest that selective and individualized para-aortic assessment strategies may be considered to improve staging accuracy and optimize surgical planning in this patient population. Full article

Background/Objectives: Although the binarism between type I and II endometrial cancer was dismissed and substituted with molecular classification, histopathological features remain of paramount importance. Hence, analysing survival outcomes according to histological type, our aim is to clarify whether the morphological features of the tumour retain prognostic relevance in the context of advanced disease. Methods: This is a retrospective analysis led within the Thames Valley Cancer Alliance Network. Results: We include 148 FIGO 2009 stage III–IV patients affected by endometrioid endometrial cancer (EEC) G1, G2, and G3, carcinosarcoma (CS), serous carcinoma (SC), and clear cell carcinoma (CCC) of the uterus. Five year overall survival (OS) is distinct among the histological groups (p-value < 0.001), being 73.3% for G2 endometrioid, 49.2% for G3 endometrioid, 8.3% for CS, and 28.4% for SC. The divergence was marked also for 5 year progression-free survival (PFS) (p-value < 0.001) as follows: for G2 endometrioid, was 76.4%; for G3 endometrioid, 52.7%; and for carcinosarcoma, 5.9%. PFS after 18 months for serous carcinoma was 5.7%. The multivariate analysis found G3 endometrioid (HR 2.91, 95% CI 1.20–7.11, p-value 0.018), carcinosarcoma (HR 12.15, 95% CI 5.07–29.11, p-value < 0.001), and serous carcinoma (HR 4.84, 95% CI 2.16–10.83, p-value < 0.001) as independent predictors of poor survival, as well as cervical invasion (HR 1.83, 95% CI 1.10–3.05, p-value 0.020) as the only histopathological feature confirmed. Regarding progression-free only carcinosarcoma (HR 14.91, 95% CI 5.28–41.11) and serous carcinoma (HR 17.68, 95% CI 6.41–48.75) were associated with an increased risk of recurrence. Conclusions: Our findings testify that, beyond the disease stage, histological subtype remains a major determinant of survival outcome. Cervical involvement is associated with a more aggressive disease, possibly correlated to death beyond relapse. Prospective trials involving advanced stage endometrial cancer, stratified by histological subtype and integrated with the molecular classification, are required. Full article

Objective: The objective of our study was to assess the oncological safety of uterine manipulators (UMs) in apparent early-stage (FIGO I-II 2009) endometrial cancer treated by minimally invasive surgery (MIS). Methods: Our single-center retrospective study includes patients who underwent endometrial cancer surgery for apparent early-stage disease by either laparoscopy or by robotic or laparoscopic-assisted vaginal hysterectomy from November 2012 to December 2020. Data on UMs, isolated tumor cells (ITCs), cytology, lymphovascular space invasion, free cancer cells in fallopian tubes, stage, histology and grade were collected. Primary and secondary outcomes were cancer recurrence and disease-specific death. Kaplan–Meier curves and multivariate logistic regression were used for statistical analysis. Results: A total of 930 women with early-stage endometrial cancer were included; 789 (84.8%) had hysterectomy with a uterine manipulator and 141 (15.2%) without. A total of 88% had endometrioid histology, 71.6% were grade 1 and 95.7% had stage I disease. A higher risk of recurrence was observed with the Hohl manipulator (HR: 2.83. 95% CI: 1.004–7.98 p = 0.0492) on univariate analysis. On multivariate analysis, neither UM was associated with recurrence. With a mean follow-up of 48 months (range 3–118), no effect was seen on disease-specific death in either Hohl or V-Care (HR: 1.66. 95% CI: 0.48–5.70 and HR:1.29. 95% CI: 0.33–4.98). In high-grade histologies, UMs were strongly associated with recurrence (HR: 12.1. 95% CI: 1.52–96.6 p = 0.019) and disease-specific death (HR: 10.2. 95% CI: 1.12–92.1 p = 0.032). Conclusions: The use of UMs in MIS for endometrial cancer was associated with higher rates of recurrence without affecting disease-specific death, except in high-grade histologies. Full article

Background/Objectives: Several studies have suggested a contrasting link between a diabetes risk reduction diet (DRRD) pattern and cancer risk; however, their findings have been inconsistent. This study aims to systematically review observational studies and, where possible, quantify the overall effect through a meta-analysis. Methods: Searches were conducted in PubMed, Scopus, and Web of Science through May 2025. Odds ratios (ORs), along with their confidence intervals, were extracted for meta-analysis. The random-effects model was used to combine the ORs. Results: Nineteen studies met the inclusion criteria for the systematic review and meta-analysis. Of these, six reports examined the relationship between the DRRD and breast cancer risk, three assessed liver cancer incidence, two analyzed pancreatic cancer risk, and two focused on endometrial cancer. Additionally, seven studies explored the association with other cancers, including ovarian, colorectal, renal, head and neck, bladder, and lung cancers. The meta-analysis revealed that high adherence to the DRRD is associated with a decreased cancer risk (OR = 0.77, 95% confidence interval [95% CI]: 0.71–0.84, p < 0.001). Conclusions: After stratifying by geographic region, gender, study design, and cancer site, the inverse relationship remained significant across all subgroups. DRRD can be viewed as a beneficial approach associated with a lower cancer risk. Full article

Objectives: This study aimed to evaluate the introduction of sentinel lymph node biopsy (SLNB) in early-stage endometrial cancer (EC), its learning curve, and factors influencing discrepancies between surgeons and pathologists. Methods: A single-centre retrospective observational study was conducted from June 2019 to December 2024 at the Department of Obstetrics and Gynecology, University Hospital Brno and Faculty of Medicine, Masaryk University. Patients with EC with complete preoperative staging and planned for extrafascial hysterectomy with bilateral salpingo-oophorectomy and SLNB were included. Bilateral detection rates were compared among two main surgeons—one senior fellow (A) and one junior fellow (B)—and other supervised fellows. Learning curves were assessed using detection rates and cumulative sum analysis. Risk factors for failed detection were analysed. Results: In 337 patients, overall bilateral detection rates ranged from 80–92%. Surgeon A achieved 80% success by the 30th procedure and 89% at the 74th. Surgeon B, trained under A’s supervision, reached 89% but later showed a decline after operating independently. The highest concordance with pathologists was noted for Surgeon A (94.6%), followed by B (92.2%) and others (84.9%). Discrepancies were mainly associated with the presence of fibroids (p = 0.005) and adenomyosis (p = 0.018). Conclusions: SNB in EC demonstrates an optimal learning curve that can be shortened through expert guidance. Extending supervised training to 30–35 procedures reduces post-independence decline and sustains high detection rates. Bilateral success, reflecting surgeon–pathologist concordance, is a strong indicator of the quality of a Gynecologic Oncology centre. Full article

Background: The incidence of endometrial cancer (EC) is rising globally across all age groups. Endometrial intraepithelial neoplasia (EIN) is a premalignant lesion that may progress to EC if untreated. A clinical model is needed to efficiently identify women requiring prompt evaluation while avoiding unnecessary invasive procedures. Obesity is a major risk factor, but whether Asian women require a lower body mass index (BMI) cutoff than the World Health Organization (WHO) definition remains debated. This study aimed to develop a multivariable risk prediction model to guide biopsy decisions and determine an appropriate BMI cutoff for predicting EIN/EC risk among Asian women. Methods: This study retrospectively reviewed 1192 women aged ≥18 years who underwent hysteroscopy between 2010 and 2023 at a tertiary hospital. Candidate predictors included patient age, parity, BMI, postmenopausal status, symptom of abnormal uterine bleeding (AUB), diabetes mellitus, hypertension, polycystic ovary syndrome (PCOS), use of oral contraceptives, intrauterine devices, or menopausal hormone therapy, tamoxifen treatment, presence of multiple polyps, and endometrial thickness (EMT) measured by transvaginal ultrasonography. Multivariable logistic regression with stepwise selection identified independent predictors, and model stability and calibration were assessed using 1000 bootstrap resamples. Results: EIN/EC was diagnosed in 55 patients (4.6%). Six independent predictors were identified: postmenopausal status (adjusted odds ratio [aOR] 5.93, 95% CI 2.92–12.04), AUB (aOR 4.07, 1.51–10.97), multiple polyps (aOR 2.49, 1.33–4.66), PCOS (aOR 2.37, 1.08–5.22), BMI (aOR 1.13 per kg/m²; 1.84 per +5 kg/m²), and EMT (aOR 1.07 per mm, 1.02–1.11). When using categorical cutoffs, Obese II (BMI ≥ 30 kg/m²) and markedly increased EMT (≥20 mm) remained significant. Predicted probabilities ranged from 0.3% with no risk factors to 90.9% with all six risk factors present. The final model demonstrated good discrimination (AUC 0.79, 95% CI 0.73–0.86) and excellent calibration on bootstrap validation (mean absolute error 0.005). Conclusions: This six-factor clinical model stratifies individual EIN/EC risk using readily available variables and may guide timely, risk-based biopsy decisions by identifying high-risk patients while minimizing unnecessary procedures in low-risk cases. BMI ≥ 30 kg/m² (WHO obesity threshold) was confirmed as a meaningful cutoff, but external validation is warranted to confirm its generalizability and clinical applicability. Full article

Background and Objectives: Previous surgical approach comparisons in endometrial cancer may be confounded by inadequate control for tumour biology—the primary driver of outcomes. This study provides the first surgical approach comparison incorporating molecular classification to control for case selection bias. Materials and Methods: Retrospective analysis of 512 consecutive patients with stage I–II endometrial cancer (FIGO 2009) treated with open (n = 83), laparoscopic (n = 278), or robotic (n = 151) surgery between 2018 and 2024. Molecular classification was available for 219 patients (42.8%) using TCGA criteria and incorporated into analyses to control for case selection bias, with molecular subtype incorporated to control for biological bias rather than as a primary endpoint. Primary outcomes included perioperative metrics and oncological safety. The primary objective was to determine whether apparent surgical outcome differences reflect genuine technique effects or case selection bias based on tumour biology. Results: Molecular subtype distribution varied significantly by surgical approach, with high-risk subtypes concentrated in open surgery, explaining apparent outcome differences. After controlling for molecular subtype and other confounders, minimally invasive approaches demonstrated superior perioperative outcomes: reduced blood loss (laparoscopic 129.8 mL, robotic 157.9 mL vs. open 261.4 mL, p < 0.001), shorter hospital stays (2.4 and 2.2 vs. 5.3 days, p < 0.001), and lower complications (5.7% and 6.6% vs. 21.6%, p < 0.001). In our cohort, recurrence-free survival showed significant differences favouring minimally invasive approaches, with 2-year RFS rates of 92.8%, 96.4%, and 100.0% (p = 0.008) and 3-year RFS rates of 90.4%, 95.0%, and 100.0% (p = 0.003) for open, laparoscopic, and robotic surgery, respectively, although robotic surgery had a shorter follow-up (median 33 vs. 42 months). Within-approach exploratory analyses revealed that p53-abnormal tumours were associated with significantly longer operative times and greater blood loss across all surgical approaches (p < 0.05), although complication rates did not differ significantly by molecular subtype within any approach (open p = 0.124, laparoscopic p = 0.656, robotic p = 0.287). Apparent surgical approach differences largely reflected appropriate case selection based on tumour biology rather than technique superiority. Conclusions: When controlling for tumour biology, minimally invasive approaches offer superior perioperative outcomes with equivalent oncological safety. Higher complication rates in open surgery primarily reflect the inherent morbidity of this approach and appropriate surgeon selection for high-risk cases. Within-approach analyses suggest possible molecular influences on operative parameters that warrant prospective validation. Molecular stratification is essential for fair surgical approach comparison in the contemporary era. Full article

Objective: Obesity increases the risk of endometrial cancer (EC). In this study, we aimed to investigate the prognostic effect of sarcopenia, sarcopenic obesity and sarcopenic visceral obesity, calculated with the help of cross-sectional imaging methods of muscle and visceral adipose tissue from body composition parameters, in EC. Methods: Patients diagnosed with EC were identified between January 2014 and June 2024. The combination of radiological markers and patient outcomes can predict prognosis. The skeletal muscle index (SMI) and visceral fat index (VFI) were calculated from computed tomography (CT) and/or abdominal magnetic resonance (MR) scans taken at the time of diagnosis at the Lumbal 3 (L3) vertebra level. The findings of these analyses demonstrate the strongest correlation with the ratio of muscle and visceral fat tissue throughout the body. The loss of muscle and fat is an unfavourable indicator in patients with EC. The present study analysed the prognostic values of sarcopenia, sarcopenic obesity, sarcopenic visceral obesity, and the visceral fat index in EC. The total skeletal muscle area was calculated in square centimetres. Body surface area (m²) was calculated using the Mosteller formula: ((height (cm) × weight (kg))/3600)^1/2. To normalize body composition components, the skeletal muscle index was calculated as cm²/m². Results: The study comprised a total of 236 EC patients. The prevalence of sarcopenia, sarcopenic obesity, and sarcopenic visceral obesity were found to be 48.31%, 33.47%, and 22.88%, respectively. The presence of sarcopenia, high VFI levels, sarcopenic obesity, and sarcopenic visceral obesity did not demonstrate statistical significance in the survival analysis. However, stage increase (p = 0.001), primary tumour localization in the lower uterine segment (p = 0.001), serous carcinoma (p = 0.001), increased grade in endometrioid carcinoma (p = 0.023), and lymphovascular invasion (p = 0.001) were significantly associated with increased mortality risk. The presence of sarcopenia was found to be significant in patients with obesity (p = 0.008) and those aged ≥ 65 years (p = 0.001). Conclusions: In EC survival, established prognostic factors such as serous histopathology, LVI positivity, and the extent of surgical staging are prioritised. The presence of these well-established markers means the potential effect of BMI-based observations, such as the ‘obesity paradox’, and even body composition measurements, such as sarcopenic obesity, are now statistically insignificant. Our findings suggest that aggressive tumour biology (serous type, LVI) and surgery, rather than metabolic variables such as sarcopenia, sarcopenic obesity and sarcopenic visceral obesity, are the direct reason for the survival difference. This is due to the tumour’s aggressive nature and clinical characteristics (e.g., age at diagnosis, operability, stage, primary tumour localization in the lower uterine segment, serous carcinoma, grade, and LVI positivity) rather than metabolic variables. Full article

Background: Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. While early-stage disease has favorable outcomes, advanced or recurrent EC remains associated with poor prognosis. Novel prognostic markers are needed to refine risk stratification. Systemic inflammation-based indices such as Pan-Immune Inflammation Value (PIV), Systemic Inflammation Response Index (SIRI), and Systemic Immune Inflammation Index (SII) have shown prognostic potential in solid tumors. Methods: We retrospectively evaluated 78 patients with endometrioid EC who had undergone hysterectomy with adnexectomy and lymphadenectomy. Demographic, clinicopathological, and laboratory data were extracted from electronic medical records. PIV, SII, and SIRI were calculated from the preoperative complete blood counts. Survival was assessed using Kaplan–Meier analysis, while prognostic factors were determined using univariate and multivariate Cox regression analyses. Results: The median age was 59 years, and 64.1% of the patients presented with early-stage disease. A high PIV (≥802) was significantly associated with a shorter overall survival (64 vs. 111 months, p < 0.001). PIV demonstrated the highest discriminatory accuracy (AUC = 0.776), followed by the SII (0.747) and SIRI (0.718). Univariate analysis identified that age, grade, LVSI, PNI, stage, distant metastasis, and high PIV, SII, SIRI, and NLR were predictors of poor survival. Multivariate analysis confirmed grade, distant metastasis and SIRI ≥ 1.5 as independent prognostic factors. Conclusions: Inflammation-based indices, particularly PIV and SIRI, correlated with survival outcomes in patients with EC. The SIRI retained an independent prognostic value, whereas PIV showed a strong discriminatory capacity. Incorporating these indices into established risk models may improve prognostic precision and support individualized management. Full article

Background/Objectives: Despite advances in targeted therapies, a substantial proportion of high-risk endometrial carcinomas (EC) do not respond to treatment and have a poor prognosis. The identification of prognostic and predictive biomarkers to improve patient stratification is therefore a clinical priority. L1 cell adhesion molecule (L1CAM) is a promising biomarker in EC; however, its soluble circulating form (sL1CAM) has been poorly investigated. This study aimed to evaluate the prognostic and predictive significance of sL1CAM in high-risk ECs. Methods: High-risk EC patients, treated with surgery and platinum-based adjuvant chemotherapy, were retrospectively enrolled. sL1CAM levels were quantified in 72 preoperative serum samples by enzyme-linked immunosorbent assay (ELISA). Results: High sL1CAM levels were associated with advanced age and non-endometrioid histology. Across the entire patient cohort, higher sL1CAM concentrations significantly correlated with worse prognosis in terms of DSS and PFS in univariate (DSS: HR = 2.22, p = 0.028; PFS: HR = 1.21, p = 0.041) and multivariate (DSS: HR = 2.13, p = 0.041; PFS: HR = 1.93, p = 0.048) analyses. Stratification by histological type revealed a significant prognostic association only in the endometrioid subgroup, both in univariate and multivariate analyses. Moreover, in this subgroup, elevated sL1CAM levels were associated with shorter time to recurrence after chemotherapy, both in univariate (PFI: HR = 2.69, p = 0.027) and multivariate (PFI: HR = 2.97, p = 0.017) analysis, and significantly predicted relapse within 6 months (OR = 7.83, p = 0.027). Conclusions: sL1CAM is associated with poor prognosis in high-risk EC and seems to be associated with platinum response in endometrioid tumors. These findings support its potential role as a biomarker to improve risk stratification, warranting validation in larger, prospective studies. Full article