International Journal of Gynecological Cancer最新文献

Mucinous ovarian cancer is a rare and molecularly distinct sub-type of epithelial ovarian cancer, characterized by intrinsic resistance to cytotoxic chemotherapy and poor prognosis in advanced stages, with a median overall survival of 12 to 34 months. Its low incidence (<3% of advanced epithelial ovarian cancers) limits the feasibility of large-scale clinical trials, underscoring the need for molecularly informed therapeutic strategies. Oncogenic activation of the mitogen-activated protein kinase (MAPK) pathway (most commonly through KRAS mutations [50%-65%] and near-universal MAPK hyperactivation) constitutes a defining feature of mucinous ovarian cancer biology and a rational therapeutic target. Despite this, there are no clinical data specifically evaluating MAPK-targeted therapies to date. Insights from other KRAS-driven malignancies reveal major challenges, including adaptive resistance, activation of compensatory signaling pathways (eg, PI3K/AKT), and intratumoral heterogeneity. This review synthesizes translational evidence for MAPK pathway targeting in mucinous ovarian cancer and proposes a clinical framework for treatment selection by integrating KRAS/MAPK activation with epidermal growth factor receptor/human epidermal growth factor receptor 2 (EGFR/HER2) signaling, PI3K pathway alterations, and tumor-immune features. As comprehensive molecular profiling advances, integrated targeting of the rat sarcoma-rapidly accelerated fibrosarcoma-mitogen-activated protein kinase kinase-extracellular signal-regulated kinase (RAS-RAF-MEK-ERK) cascade may offer promising and urgently needed therapeutic strategies for this rare malignancy.

Objective: The 2025 endometrial carcinoma risk classification by the European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) integrates new pathologic and molecular features. We evaluated its clinical impact and prognostic performance in comparison with the 2021 system.

Methods: This retrospective single-center cohort study included patients categorized according to the 2021 and 2025 risk classifications. Immunohistochemistry and POLE sequencing were conducted for molecular classification and estrogen receptor determination.

Results: We identified 1115 patients with 2021 and 2025 risk classifications (median follow-up: 66 months; range; 0-136). The update re-classified 117 patients (10.5%) into a different risk group: 68 (6.1%) downward, 24 (2.2%) upward, 16 (1.4%) from uncertain to defined, and 9 (0.8%) from defined to uncertain. Both classification systems were prognostic (pooled p < .001 across strata). In pairwise comparisons, the 2025 system did not distinguish high-intermediate-risk from high-risk disease (p = .15 and p = .25 for progression-free survival and disease-specific survival). The 2021 system showed better progression-free survival for high-intermediate-risk compared with high-risk disease (p = .026), but not disease-specific survival (p = .06). Estrogen receptor negativity, which modifies risk in localized low-grade no-specific-molecular-profile carcinomas, was rare in this category (4 [1.3%] negative vs 307 [98.7%] positive). Lymph node involvement (stage IIIC1i-IIIC2ii) differed across molecular tumor categories: 3.0% in POLE-ultra-mutated, 8.7% in mismatch repair-deficient, 5.0% in low-grade and estrogen receptor-positive no-specific-molecular-profile, 13.0% in high-grade or estrogen receptor-negative no-specific-molecular-profile, and 16.5% in p53-abnormal tumors (p < .001).

Conclusions: The ESGO-ESTRO-ESP 2025 classification re-assigns approximately one-tenth of patients, with a meaningful impact on adjuvant therapy. The rarity of estrogen receptor negativity limits its role in no-specific-molecular-profile stratification. Variation in lymph node involvement across molecular tumor categories highlights opportunities for individualized surgical staging.

Objective: Single-port robotic surgery is an emerging technology in Europe, offering potential advantages for minimally invasive gynecologic procedures. However, its application in gynecologic oncology remains limited, and evidence regarding its feasibility, safety, and technical challenges is scarce. This study aimed to prospectively evaluate the feasibility and safety of single-port robotic surgery in gynecologic oncology within a high-volume referral center.

Methods: We conducted a prospective cohort study of all consecutive patients who underwent a single-port robotic approach for suspected or confirmed gynecologic cancer at the European Institute of Oncology, Milan, between July 2024 and June 2025. Surgical procedures were performed by a dedicated gynecologic oncology team following international guidelines. Patient demographics, intra-operative characteristics, and post-operative outcomes were prospectively collected.

Results: A total of 63 patients were included, with a median age of 57 years (inter-quartile range, [IQR]; 46-65) and a median body mass index of 24.4 kg/m² (IQR; 22.0-27.3). Endometrial cancer was the most common indication (47.6%). All procedures were completed without conversion to multi-port or open surgery. Median operative time was 131 minutes (IQR; 105-155), and median estimated blood loss was 50 mL (IQR; 30-100). No intra-operative complications occurred. Post-operative pain was minimal, with median Numerical Rating Scale scores of 1 at all assessed time points. The median hospital stay was 2 days (IQR; 2-2). Three major post-operative complications occurred within 30 days (4.8%), all managed surgically: 2 pelvic hematomas and 1 pelvic abscess.

Conclusions: Single-port robotic surgery appears feasible and safe for selected patients with gynecologic malignancies, with no conversions and no intra-operative complications. However, larger, multi-institutional studies with longer follow-up are needed to confirm oncologic safety and define its role in practice.

Ovarian cancer is a leading cause of cancer-related mortality among women, with poor prognosis and limited survival in advanced stages. The integration of artificial intelligence with omics data offers new opportunities to enhance the diagnosis, prognosis, and treatment of this disease. This narrative review synthesizes evidence from 14 studies published between 2021 and 2024 that applied artificial intelligence to genomic, transcriptomic, metabolomic, micro-biomic, and epigenomic data sets in patients with epithelial ovarian cancer. These studies explored artificial intelligence models for disease detection, chemotherapy response prediction, and genetic risk stratification. Despite promising results (eg, high classification accuracy and area under the curve values in some models), significant limitations were observed, including small sample sizes, retrospective and single-center designs, and inconsistent use of validation data sets. The review highlights critical methodological considerations such as data preprocessing, normalization, and feature selection, which substantially influence model performance and reproducibility. Although classification models (eg, deep learning, random forest, and support vector machines) were most commonly used, regression approaches were less frequent and under-used, despite their value for modeling continuous outcomes such as survival time. Overall, artificial intelligence-based approaches demonstrate great potential for advancing personalized medicine in ovarian cancer. However, future research must prioritize larger, multi-center, prospective studies with robust validation strategies and improved model interpretability to enable clinical implementation.

Objective: Platinum-resistant ovarian cancer remains a major therapeutic challenge, with limited benefit from currently available cytotoxic agents. Elenagen is a newly developed plasmid DNA-based anti-cancer agent that encodes p62/SQSTM1 protein, a multi-functional adapter protein involved in selective autophagy, signal transduction, and modulation of the inflammatory response. We previously reported the progression-free survival outcomes of patients with platinum-resistant ovarian cancer treated with Elenagen. We report the overall survival results from a phase II randomized controlled trial comparing Elenagen plus gemcitabine with gemcitabine alone.

Methods: This open-label, prospective, randomized, 2-center study enrolled women with platinum-resistant ovarian cancer. Patients were randomly assigned (1:1) to receive gemcitabine monotherapy (1000 mg/m² on days 1 and 8 every 21 days) or gemcitabine plus Elenagen (2.5 mg intra-muscularly weekly). The primary end point was overall survival; secondary end points included safety, post-progression outcomes, and time-dependent analyses of Elenagen exposure. Survival was analyzed using Kaplan-Meier and Cox proportional hazards models.

Results: Thirty patients (15 per arm) were evaluable for overall survival. Baseline demographic and clinical characteristics were balanced between groups. Among patients with elevated CA-125 levels (> 35 U/mL), median overall survival was 13 months (95% confidence interval [CI] 10 to 27) in the gemcitabine arm and 25 months (95% CI 17 to not reached) in the Elenagen plus gemcitabine arm (log-rank p = .031). Treatment with Elenagen was associated with a 59% reduction in the risk of death (hazard ratio 0.41, 95% CI 0.18 to 0.94, p = .036). Time-dependent and landmark analyses demonstrated a positive association between longer Elenagen exposure and improved survival (p < .001). No additional safety signals were observed compared with gemcitabine alone. Post-progression survival and subsequent therapy patterns were comparable between arms.

Conclusions: The addition of Elenagen to gemcitabine prolonged overall survival in patients with platinum-resistant ovarian cancer without increasing toxicity.

Trial registration: NCT05979298, 2023-08-07.