Menopausal Status Combined with Serum CA125 Level Significantly Predicted Concurrent Endometrial Cancer in Women Diagnosed with Atypical Endometrial Hyperplasia before Surgery

About 10–66% of patients with atypical endometrial hyperplasia diagnosed before surgery (preoperative-AEH) are found to have concurrent endometrial cancer (EC) at definitive hysterectomy, leading to incomplete primary surgery and delayed adjuvant treatment. This study aims to investigate the potential risk factors of concurrent EC in preoperative-AEH patients in a clinical setting with a gynecological pathology review. All patients diagnosed with AEH by endometrial biopsy or curettage that then underwent definitive hysterectomy from January 2016 to December 2019 in a tertiary hospital were retrospectively analyzed. All diagnoses were reviewed by gynecological pathologists. A total of 624 preoperative-AEH patients were included, 30.4% of whom had concurrent EC. In multivariate analysis, postmenopausal status and CA125 ≥ 35 U/mL significantly correlated with concurrent EC (OR = 3.57; 95% CI = 1.80–7.06; OR = 2.15; 95% CI = 1.15–4.03). This risk was remarkably increased in patients with both postmenopausal status and CA125 ≥ 35 U/mL (OR = 16.20; 95% CI = 1.73–151.44). Notably, concurrent EC seemed to occur more frequently in women with postmenopausal time ≥ 5 years (OR = 4.04, 95% CI = 1.80–5.85). In addition, CA125 ≥ 35 U/mL seemed to be an independent risk factor (OR = 5.74; 95% CI = 1.80–18.27) for concurrent intermediate-high-risk EC. Intermediate-high-risk EC was also more commonly seen in preoperative-AEH women with postmenopausal time ≥ 5 years (OR = 5.52, 95% CI = 1.21–25.19, p = 0.027). In conclusion, preoperative-AEH patients with postmenopausal status or elevated level of CA125 might have a high risk of concurrent EC. Adequate pre-surgical evaluation might be suggested for such patients.

Maintenance Therapy Can Improve the Oncologic Prognosis and Obstetrical Outcome of Patients With Atypical Endometrial Hyperplasia and Endometrial Cancer After Fertility-Preserving Treatment: A Multicenter Retrospective Study

ObjectiveTo evaluate the effect of maintenance therapy for patients with atypical endometrial hyperplasia (AEH) and early endometrial cancer (EC) after successful fertility-preserving management on prognosis and pregnancy outcome.MethodsWe performed a retrospectively analysis of 109 young women with atypical endometrial hyperplasia and early endometrioid endometrial cancer who had received complete response after fertility-preserving treatment at 5centers between May 2005 and March 2021. Maintenance therapy regimes included low-dose oral progesterone, levonorgestrel intrauterine device(LNG-IUD) and combination oral contraceptive (COC). The patients were divided into two groups, maintenance therapy group and non-maintenance therapy group. Clinical characteristics, treatment regimens, prognosis, and pregnancy outcome were compared between the two groups.ResultsThe overall disease recurrence rate of the maintenance therapy group was significantly lower than that of the non-maintenance therapy group (P < 0.001). The recurrence rate of atypical endometrial hyperplasia and endometrial cancer in the maintenance therapy group were significantly lower than those in the non-maintenance group (P < 0.001). Maintenance therapy can reduce pregnancy rates and live birth rates. Maintenance therapy can protect the endometrium in patients treated with assisted reproductive technology (ART), greatly reducing the recurrence rate after ART (P<0.001).ConclusionMaintenance therapy plays a very important protective role in fertility-preserving treatment for patients with atypical endometrial hyperplasia and endometrial cancer, which could significantly reduce the risk of recurrence. It is recommended that patients could receive maintenance therapy as long as possible during the period from achieving complete response to pregnancy preparation if possible. It may provide recurrence-free survival long enough for childless young women to prepare for pregnancy in the future. It can also protect the endometrium of those who are preparing to use assisted reproductive technology, possibly by reducing the risk of recurrence by excessive stimulation with assisted reproductive drugs.

Insulin Resistance and Metabolic Syndrome Increase the Risk of Relapse For Fertility Preserving Treatment in Atypical Endometrial Hyperplasia and Early Endometrial Cancer Patients

ObjectiveFertility-sparing treatment for young women with atypical endometrial hyperplasia (AEH) and early endometrial cancer (EC) is a difficult challenge. Insulin resistance (IR) and metabolic syndrome (MetS) are two potentially crucial, but currently enigmatic factors in the recurrence of AEH and early EC patients. In this study we attempt to elucidate these factors.MethodsA retrospective study was conducted from January 2010 to December 2019. Risk factors for recurrence and complete remission time after recurrence (RCR time) were investigated. ROC curves were built to estimate the accuracy of the metabolic characteristics and Kaplan–Meier (K–M) analysis was used to calculate recurrence-free survival (RFS) for patients with various IR or MetS statuses.ResultsA total of 111 AEH or early EC patients met the criteria and were enrolled in our study. Univariate analysis found that BMI ≥25 kg/m2 (OR = 2.7, 95% CI: 1.1–6.4, P = 0.03), IR (OR = 9.5, 95% CI: 3.3–27.0, P <0.001), MetS (OR = 4.9, 95% CI:1.5–15.5, P = 0.008), IR+ and MetS+ (OR = 21.0, 95% CI: 4.8–92.7, P <0.001), histological type (OR = 3.5, 95% CI: 1.5–7.9, P = 0.003), and maintenance treatment (OR = 0.3, 95% CI: 0.1–0.6, P = 0.005) were all significantly associated with recurrence and longer RCR time. Among these factors, IR and MetS were determined to be two independent risk factors for recurrence. Moreover, using IR and MetS as markers significantly improved the diagnostic accuracy of recurrence for fertility-sparing treatment patients (AUC = 0.818, P <0.05) and may play synergistic roles in suppressing treatment. K–M analysis indicated both metabolic features played important roles in RFS (P <0.05).ConclusionBoth IR and MetS were significantly associated with recurrence and longer RCR time in AEH and early EC patients receiving fertility-sparing treatment.

Outcomes of women treated with progestin and metformin for atypical endometrial hyperplasia and early endometrial cancer: a systematic review and meta-analysis

ObjectiveProgestin therapy is the recommended fertility-sparing management of atypical endometrial hyperplasia or early-stage endometrial cancer in reproductive-aged women. Our objective was to evaluate disease relapse after progestin and metformin versus progestin therapy alone in patients with endometrial hyperplasia or cancer. Our secondary outcomes were disease remission, clinical pregnancy and live birth rate.MethodsA systematic review of the literature was conducted (MEDLINE, Web of Science, Cochrane Library, CINAHL, LILACS, clinicaltrials.gov) from inception to April 2021. Studies of reproductive-aged women with atypical endometrial hyperplasia or early endometrial cancer who received progestin and metformin or progestin alone for fertility-sparing management, were included in the review. Early endometrial cancer was defined as grade 1, stage 1 disease. Exclusion criteria included women with higher grade endometrial cancer and when conservative management was not for fertility-sparing purposes. Data are presented as odds ratios (ORs) and 95% confidence intervals (CIs) with fixed or random effects meta-analysis. Quality scoring was based on the Newcastle-Ottawa and Jadad scales.ResultsIn total, 271 reports were identified and six studies met the inclusion criteria. These studies included 621 women; 241 (38.8%) patients received combined therapy and 380 (61.2%) received progestin therapy alone. Relapse rates were lower for progestin and metformin than for progestin therapy alone (pooled OR 0.46, 95% CI 0.24 to 0.91, p=0.03). The remission rates were not different (pooled OR 1.35, 95% CI 0.91 to 2.00, p=0.14). Women who received progestin and metformin achieved pregnancy and live birth rates similar to those who received progestin therapy only (pooled OR 1.01, 95% CI 0.44 to 2.35, p=0.98; pooled OR 0.46, 95% CI 0.21 to 1.03, p=0.06).ConclusionFor reproductive-aged women with atypical endometrial hyperplasia or early endometrial cancer, progestin and metformin therapy compared with progestin therapy alone is associated with lower relapse rates, and similar remission, clinical pregnancy and live birth rates.PROSPERO registration numberCRD42020179069.disease remission,