Yiqin Wang

Analysis of fertility-preserving treatment outcomes in patients with POLE-mutated endometrioid carcinoma

To explore the clinical outcomes of fertility-sparing treatment (FST) in patients with POLE-mutated endometrioid carcinoma (EEC). A total of 9 EEC patients who received FST and were classified to the POLE-mutated subtype in Peking University People's Hospital from April 2020 to October 2023, were retrospectively collected. Clinical and pathological data were analyzed to describe the outcomes of FST in patients with POLE-mutated EEC. A total of 9 patients with EEC including 6 cases with well-differentiated (G1) and 3 cases with moderately-differentiated (G2). The average age was 34.8±2.1 years. POLE mutation sites were P286R (5 cases), V411L (2 cases), L424I (1 cases), and S459F (1 cases), respectively. The median follow-up time was 16 months (9-41 months). The complete response (CR) rate was 88.9% (8/9), with a median time to CR of 5.5 months (3-18 months). The partial response (PR) rate was 11.1% (1/9). The relapse rate was 50.0% (4/8), with a median recurrence time of 9.5 months (5-25 months). Of these, 75% (3/4) underwent secondary FST, with all achieving CR again (3/3). Three of 5 who were out-of-indication patients achieved CR by individual therapy. FST in patients with POLE-mutated EEC achieve a CR rate of 88.9% in this study, the largest number of retrievable reports. In certain patients who are out-of-indication, individualized treatment may also result in remission. However, unlike surgical patients, some patients experience disease recurrence and whether POLE-mutated EEC is sensitive to conventional therapy in FST is controversial given its pathogenesis.

Diagnostic significance and predictive efficiency of metabolic risk score for fertility-sparing treatment in patients with atypical endometrial hyperplasia and early endometrial carcinoma

This study aims to assess the impact of the metabolic risk score (MRS) on time to achieve complete remission (CR) of fertility-sparing treatments for atypical endometrial hyperplasia (AEH) and early endometrial cancer (EC) patients. Univariate and multivariate cox analyses were employed to identify independent risk factors affecting the time to CR with patients at our center. These factors were subsequently incorporated into receiver operator characteristic curve analysis and decision curve analysis to assess the predictive accuracy of time to CR. Additionally, Kaplan-Meier analysis was utilized to determine the cumulative CR rate for patients. The 173 patients who achieved CR following fertility preservation treatment (FPT) were categorized into three subgroups based on their time to CR (9 months). Body mass index (hazard ratio [HR]=0.20; 95% confidence interval [CI]=0.03, 0.38; p=0.026), MRS (HR=0.31; 95% CI=0.09, 0.52; p=0.005), insulin resistance (HR=1.83; 95% CI=0.05, 3.60; p=0.045), menstruation regularity (HR=3.77; 95% CI=1.91, 5.64; p=0.001), polycystic ovary syndrome (HR=-2.16; 95% CI=-4.03, -0.28; p=0.025), and histological type (HR=0.36; 95% CI=0.10, 0.62; p=0.005) were identified as risk factors for time to CR, with MRS being the independent risk factor (HR=0.29; 95% CI=0.02, 0.56; p=0.021). The inclusion of MRS significantly enhanced the predictive accuracy of time to CR (area under the curve [AUC]=0.789 for Model 1, AUC=0.862 for Model 2, p=0.032). Kaplan-Meier survival curves revealed significant differences in the cumulative CR rate among different risk groups. MRS emerges as a novel evaluation system that substantially enhances the predictive accuracy for the time to achieve CR in AEH and early EC patients seeking fertility preservation.

Molecular Classification Guides Fertility-Sparing Treatment for Endometrial Cancer and Atypical Hyperplasia Patients

Objectives: The objective of this study was to investigate the significance of molecular classification in guiding treatment decisions for patients with endometrial cancer (EC) or atypical hyperplasia (AH) undergoing fertility-sparing treatment (FST), particularly for those with non-NSMP subtypes. Methods: We conducted a retrospective cohort study involving EC/AH patients undergoing FST and molecular classification using next-generation sequencing at Peking University People’s Hospital between June 2020 and September 2023. Results: A total of 118 EC/AH patients were included, including 92 cases with NSMP, 11 with MMRd, 11 with POLEmut, and 4 with p53abn. (1) Of the 11 patients with MMRd, 6 achieved a complete response (CR) with 1 case receiving progestin, 3 cases showed insensitivity to the initial progestin before transitioning to a combined regimen of progestin and a PD-1 inhibitor, and 2 cases initially received progestin plus a PD-1 inhibitor. There were no significant differences in the cumulative CR rates between the MMRd and NSMP subgroups but a trend of a lower relapse-free-survival (RFS) rate for the MMRd subgroup (p = 0.074). (2) Of the 11 cases with POLEmut, 10 achieved CR but 4 relapsed. There was also a trend for a lower RFS rate in the POLEmut patients (p = 0.069) compared with the NSMP subgroup. (3) Three of the four patients with p53mut achieved CR after treatment with the GnRHa plus LNG-IUS regimen. Conclusion: The selection of appropriate regimens may improve FST outcomes in EC/AH patients with molecular classification of non-NSMP subtypes. Immunotherapy is an effective fertility-preserving approach for patients with MMRd.

Fertility-sparing treatment outcomes using immune checkpoint inhibitors in endometrial cancer patients with Lynch syndrome

To evaluate the efficacy of immune checkpoint inhibitors (ICIs) for fertility-sparing treatment in Lynch syndrome-associated endometrial cancer (LS-EC). Four LS-EC cases received programmed cell death protein 1 (PD-1) inhibitors for fertility preservation at the Obstetrics and Gynecology Hospital of Fudan University from 2017 to 2023. The clinical data and long-term outcomes were retrospectively reviewed. Case 1, carrying germline ICIs might be an effective choice for LS-EC patients desiring fertility preservation.

Constructing a prediction model for lymph node metastasis in patients with incidental finding of endometrial cancer based on Fully-Connected Network

Rare studies focused on patients with incidental diagnosis of endometrial cancer (EC) after hysterectomy. We intended to construct a prediction model of lymph node metastasis (LNM) based on Fully-Connected Network (FC Network) for these patients. A total of 3,920 cases of EC that met the criteria from Obstetrics & Gynecology Hospital of Fudan University between January 2016 and February 2023 and 1995 cases from Fudan University Shanghai Cancer Center between January 2013 and October 2020 were retrospectively included for the construction of a predicting model which was based on FC Network. At the same time, 572 cases were prospectively collected for external validation. The sensitivity of the model was 0.946. Lympho-vascular space invasion, myometrial invasion, tumor grade, microcystic elongated and fragmented invasion, progesterone receptor, and cancer antigen 125 were used to construct a simplified nomogram. The area under the curve of the nomogram was 0.890 and 0.885 in validation and prospective cohorts, respectively. The model we proposed has good sensitivity and can be used to predict the risk of LNM in patients with incidentally found EC. The simplified nomogram can be used as a substitute in certain situations. Based on another study, the threshold of 5% and 25% can be used for risk stratification.

Is it safe to preserve uterus after live birth following progestin‐based fertility‐sparing treatment for endometrial cancer or atypical hyperplasia: A long‐term retrospective cohort study

Abstract Introduction We aimed to assess the safety of continuous uterus‐preserving treatment among patients with endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) who gave birth after progestin‐based fertility‐sparing treatment (FST). Material and Methods From January 2005 to June 2020, we conducted a retrospective cohort study at Peking University People's Hospital, China, comprising 212 patients with EC or AEH who underwent FST. The participants were categorized into two groups based on the reproductive outcome of live birth. Risk factors were analyzed for disease recurrence in the entire cohort, and additional analysis was conducted on postpartum recurrence specifically in the live birth group. Results Of 212 eligible patients, 73 had a live birth, and 139 did not have a live birth after FST. Multivariable Cox analysis showed that live birth significantly reduced the risk of disease recurrence (HR 0.326, p  = 0.011), while insulin resistance was identified as an adverse factor (HR 3.216, p  = 0.014). Except for two patients who underwent hysterectomy, among 71 patients undergoing uterus preservation after live birth, five (7%) patients experienced disease relapse (two EC and three AEH) after a median follow‐up of 26 (11, 47.5) months. Four out of these five patients with recurrence achieved a complete response after a second round of FST. Eight other patients (11.3%) experienced hyperplasia without atypical (EH) after live birth. Potential risk factors for postpartum recurrence of EC/AEH included irregular menstruation (80% vs. 39%; p  = 0.153), abnormal ultrasonographic findings (60% vs. 18.6%; p  = 0.065), and increased endometrial thickness (0.82 cm vs. 0.55 cm; p  = 0.017). While postpartum maintenance therapy was identified as a protective factor against recurrence (0% vs. 62.5%; p  = 0.012). Notably, patients with postpartum recurrence may achieve a complete response with repeat FST. Conclusions Although live birth was associated with improved recurrence‐free survival in patients with EC or AEH receiving FST, postpartum recurrence remains a concern. Irregular menstruation and abnormal ultrasound findings were identified as key risk factors for recurrence, while maintenance therapy exhibited a protective effect. These findings highlight the need for vigilant postpartum monitoring in this population.