To evaluate the efficacy and safety of lenvatinib plus pembrolizumab (LP) for recurrent endometrial cancer, focusing on nonendometrioid histologic types such as carcinosarcoma and other rare variants. Patients with recurrent endometrial cancer treated with LP at Jichi Medical University Hospital between December 2021 and August 2025 were retrospectively reviewed. Out of 26 patients, 15 had endometrioid carcinoma, whereas 11 had nonendometrioid carcinoma, specifically carcinosarcoma (n=6), mesonephric-like adenocarcinoma (n=2), dedifferentiated carcinoma (n=1), mixed carcinoma (clear cell and endometrioid histology, n=1), and clear cell carcinoma (n=1). Clinical outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Prognostic factors for PFS were explored using Cox regression. The ORR and disease control rates, respectively, were 33.3% and 90.9% in nonendometrioid carcinoma, compared to 22.2% and 100% in endometrioid carcinoma. The median PFS was 6.2months for nonendometrioid and 11.5months for endometrioid carcinoma (hazard ratio [HR] 1.75, P=.295), while the median OS was 12.0 and 38.2months, respectively (HR 2.41, P=.202). On multivariate analysis, histology, platinum-free interval, and eight-week relative dose intensity were not identified as independent prognostic factors. The most frequent AEs were hypertension (92.3%) and hypothyroidism (65.4%). LP therapy demonstrated clinical activity in nonendometrioid carcinoma, including rare subtypes such as carcinosarcoma and mesonephric-like adenocarcinoma. Further accumulation of patients is warranted to validate its efficacy in these uncommon histologic types.

Background Predictive value of IGF2BP2 in combination with clinicopathological parameters for postoperative recurrence in endometrial cancer (EC): development and validation of a prognostic model. Methods This multicenter study retrospectively enrolled patients with endometrial cancer who underwent standard surgical treatment between January 2016 and January 2023. The cohort included 545 patients from the First Affiliated Hospital of Chongqing Medical University (training set) and 315 patients from two independent centers—Liangjiang Hospital of Chongqing Medical University and Women and Children’s Hospital of Chongqing Medical University (validation set). Univariate and multivariate Cox regression analyses were conducted to identify independent prognostic factors associated with recurrence-free survival (RFS), followed by the development of a nomogram-based prediction model. Model discrimination was evaluated using the area under the receiver operating characteristic curve (AUC), and calibration curves were used to assess the agreement between predicted and observed outcomes. Risk stratification was performed according to nomogram-derived scores, and the clinical applicability of the model was further validated through Kaplan-Meier survival analysis. Results Multivariate Cox regression analysis identified International Federation of Gynecology and Obstetrics(FIGO) stage (p=0.001), depth of myometrial invasion (p=0.004), histologic type (p=0.001), CA125 level (p=0.001), p53 status (p=0.013), lymphovascular space invasion (p=0.007), and IGF2BP2 expression (p<0.001) as independent prognostic factors for RFS in endometrial cancer patients. The integrated prediction model incorporating these factors demonstrated excellent performance in predicting 1-, 3-, and 5-year RFS, with significantly superior discriminative ability (AUC = 0.884) compared to single-parameter models. Conclusion The nomogram integrating IGF2BP2 with clinicopathological parameters demonstrates robust accuracy for predicting recurrence-free survival in endometrial cancer patients. This tool provides a quantitative risk stratification framework that could potentially contribute to prognostic assessment, though its clinical implementation awaits validation in prospective studies.

DNA methylation analysis of self-collected samples has shown potential for primary endometrial cancer detection. Here, we aimed to explore DNA methylation testing as a non-invasive alternative for post-treatment surveillance. Endometrial cancer patients (n = 43) without recurrence collected pre- and post-treatment cervicovaginal self-samples and urine at home. Additionally, 17 patients with recurrence provided these samples at the time of recurrence. Healthy controls were used as reference. In total, 207 cervicovaginal self-samples and 203 urine samples were tested for nine markers (ADCYAP1, BHLHE22, CDH13, CDO1, GALR1, GHSR, HAND2, SST and ZIC1) using quantitative methylation-specific PCR. Diagnostic performance was assessed using previously established logistic regression models. In patients without recurrence, most marker levels decreased post-treatment compared to pre-treatment, in both sample types. DNA methylation positivity in cervicovaginal self-samples reduced from 90.7% pre-treatment to 19.5% post-treatment (p < .0001). In urine, a decrease from 80.5% to 20.9% was observed (p < .0001). In patients with recurrence, DNA methylation levels of CDH13, CDO1, GALR1, GHSR and HAND2 in cervicovaginal self-samples, and CDO1, GHSR and HAND2 in urine, were higher than in patients without recurrence. DNA methylation positivity was 62.5% in cervicovaginal self-samples and 58.8% in urine among patients with any recurrence, and 100% in cervicovaginal self-samples and 90.0% in urine of patients with a local recurrence specifically. These findings support methylation-based testing as a promising post-treatment surveillance method for endometrial cancer patients. This non-invasive approach could reduce the follow-up burden on patients and healthcare, alleviating challenges related to resource constraints while improving patient comfort.

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