Objective: Low-grade uterine endometrial stromal sarcoma (LG-ESS) is a rare tumor characterized by an overall good survival but showing a indolent behavior and a variable risk of recurrence. There is no clear consensus on the optimal management of these tumors and no prognostic or predictive factors have been established. With this study, we evaluated the prognostic relevance of several clinical, surgical, and pathological features in patients affected by LG-ESS to identify risk factors associated with recurrence. Methods: We retrospectively analyzed 52 LG-ESS cases, treated from January 1st, 1994, to May 31st, 2020, in two referral centers. The relationship between recurrence and clinicopathological characteristics as well as surgical treatment was investigated. Risk of recurrence and disease-free survival (DFS) were estimated by Cox regression and the Kaplan-Meier analysis, respectively. Results: Of 52 patients with LG-ESS, 8 experienced recurrence (15%). The median follow-up was 100 months (SD ± 96, range: 15–336). By univariate analysis, fragmentation/morcellation, tumor size, FIGO stage, higher mitotic count, presence of necrosis, and lymphovascular space invasion (LSVI) resulted associated with a poorer outcome. Conversely, the surgical modality (laparotomic vs laparoscopic and hysterectomy with bilateral salpingo-oophorectomy vs local excision) and pelvic lymphadenectomy were not. Even the different modalities of adjuvant therapy (hormonal therapy, radiotherapy, and chemotherapy) showed no prognostic significance. Tumor fragmentation/morcellation and higher mitotic count resulted independent prognostic variables at multivariate analysis. Conclusions: This data supports the avoidance of any type of morcellation if LG-ESS is suspected preoperatively. Higher mitotic count and, possibly, tumor size, advanced FIGO stage, necrosis, and LVSI could be exploited to tailor the adjuvant therapy, but these results need to be confirmed in larger prospective studies.

Background: There is poor evidence about sensitivity to chemotherapy according to microsatellite instability (MSI)/mismatch repair (MMR) status in endometrial cancer (EC). Methodology: The RAME study is a retrospective analysis aiming to assess response to chemotherapy in MSI-high (h) /deficient (d) MMR and MSI- low (l)/proficient (p)MMR EC patients. Primary endpoints were recurrence-free survival (RFS) for patients with localized disease and progression-free survival (PFS) and overall survival (OS) in patients with advanced/recurrent disease. Results: 312 patients treated between 2010-2022 in 4 high volume Multicenter Italian Trial in Ovarian cancer and gynecological malignancies (MITO) centers were selected. 239 patients had endometrioid EC (76.6%), 151 had FIGO stage I at diagnosis (48.9%) and 71 were MSI-h/dMMR (22.8%). Median age was 65 (range 31–91) years. Among patients with localized disease, median RFS was 100.0 months (95%CI 59.4–140.7) for MSI-l/pMMR and 120.9 months (60.0-181.8) for MSI-h/dMMR (p=0.39). Seventy-seven patients received first-line chemotherapy for advanced/recurrent disease. Patients with MSI-h/dMMR ECs had a significantly worse OS (p=0.039). In patients receiving platinum-based chemotherapy, no statistically significant difference in PFS (p=0.21) and OS (p=0.057) were detected, although PFS and OS were numerically longer in the MSI-l/pMMR population. Conclusion: Patients with metastatic MSI-h/dMMR EC receiving first-line chemotherapy had a significantly worse OS.

Background: atypical endometrial hyperplasia (AEH) is a precancerous condition implying a high risk of concurrent endometrial cancer (EC), which might be occult and only diagnosed at postoperative histopathological examination after hysterectomy. Our study aimed to investigate potential differences in preoperative clinical, sonographic, and hysteroscopic characteristics in patients with AEH and postoperative diagnosis of EC. Methods: a retrospective single-center study was carried out on a case series of 80 women with AEH undergoing diagnostic workup, including ultrasonography and hysteroscopy, with subsequent hysterectomy. Women with AEH confirmed at the histopathological examination were compared with patients with a postoperative diagnosis of EC. Results: in our population, EC was diagnosed in 53 women, whereas the preoperative diagnosis of AEH was confirmed in 27 cases. At ultrasonography, women with occult EC showed greater endometrial thickness (20.3 mm vs. 10.3 mm, p 0.001) and size of the endocavitary lesion (maximum diameter 25.2 mm vs. 10.6 mm, p 0.001), and a higher prevalence of irregular endometrial-myometrial junction (40.5% vs. 6.7%, p 0.022) and endouterine vascularization at color Doppler (64.2% vs. 34.6%, p 0.017). At hysteroscopy, patients with occult EC showed a higher prevalence of necrosis (44.2% vs. 4.2%, p 0.001) and atypical vessels (70.6% vs. 33.3%, p 0.003), whereas true AEH mainly presented as a protruding intracavitary lesion (77.8% vs. 50.9%, p 0.029). In EC, subjective assessment by the operator was more frequently indicative of cancer (80.0% vs. 12.5%). No difference was found for clinical variables. Conclusions: occult EC in AEH may exhibit some differences in ultrasonographic and hysteroscopic patterns of presentation compared with real AEH, which could prompt a more significant suspect for the possible presence of concurrent EC at preoperative diagnostic workup.

This study aimed to determine if the waist-to-hip ratio, an emerging indicator of abdominal obesity, predicts poor outcomes, such as sentinel node mapping failure, post-operative complications, conversion to laparotomy, and increased operative time, in endometrial cancer surgery. This retrospective study included patients with apparent early-stage endometrial carcinoma who underwent minimally invasive surgery at the Mauriziano Umberto I Hospital in Turin, Italy from January 2021 to January 2025. The waist-to-hip ratio was calculated using pre-operative computed tomography scans with previously described methods. Two cohorts based on a waist-to-hip ratio cutoff of 0.85, as defined by the World Health Organization, were identified and compared with statistical tests as appropriate. Univariate and multi-variable linear regression models were fit to evaluate predictors of poor surgical outcomes. A total of 151 patients were included in the study. Abdominal obesity, as defined by an abnormal waist-to-hip ratio, was identified in 127 patients (84%), of whom 62 also had obesity according to the body mass index. Patients with abnormal waist-to-hip ratios were significantly older (median: 69 vs 61 years; p = .03), had higher body mass index (median: 29 vs 21 kg/m²; p < .001), and had higher comorbidity rates (67.7% vs 33.3%; p < .001) than patients with normal ratios. Their surgical procedures were significantly longer (median: 196 vs 174 minutes; p = .01), although no differences in sentinel node mapping or post-operative complication rates were found. After adjusting for potential confounders including body mass index, an abnormal waist-to-hip ratio remained significantly associated with increased operative time, corresponding to an average increase of 22 minutes (adjusted β coefficient: 22; 95% confidence interval; 2.3-42; p = .03). An abnormal waist-to-hip ratio was significantly associated with increased operative time during minimally invasive surgery for endometrial cancer, whereas body mass index was not. Further research is needed to determine the predictive potential of the waist-to-hip ratio for personalized surgical planning.

(1) Background: In intermediate–high- and high-risk endometrial cancer (EC), radiotherapy (RT) and chemotherapy (CT) play a basic role. However, there is controversy regarding the optimal timing of their combination. The “sandwich” schedule involves adjuvant CT followed by RT and subsequent CT. The aim of this study is to assess the tolerability and efficacy of the “sandwich” schedule. (2) Methods: A retrospective study was conducted in two gynecological oncology units in Torino, Italy, from 1 January 2003 until 31 December 2021. Intermediate–high- and high-risk patients with available clinical data were included. Compliance with treatment, CT and RT toxicities, disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS) were analyzed. (3) Results: A total of 118 patients were selected: 27.1% FIGO I-II stages and 72.9% III-IV. Most of the patients (75.4%) received a carboplatin–paclitaxel combination, and as much as 94.9% of CT cycles were completed. Chemotherapy-related G3-4 toxicities were detected in 5.3% of the patients, almost half of which were hematological. Grade 2 gastrointestinal and genitourinary toxicities were reported in 8.4% and 4.2% of cases, respectively. With a median follow-up of 46 months, DFS was 77.6%, CSS was 70% and 5-year OS was 54%. (4) Conclusions: The “sandwich” schedule for CT and RT combination is an effective adjuvant treatment with low toxicity both in intermediate–high- and high-risk EC.