Abstract Background: Atypical endometrial hyperplasia (AEH) and early endometrial cancer (EEC) are common disease in menopausal women, however, are gradually increasing in women aged under 40 years. The standard treatment for AEH/EC is hysterectomy, but hormonal therapy is performed for preserving fertility. In general, fertility-preserving treatment is considered for AEH or EEC with well-differentiation and lesions confined to the endometrium without myometrial invasion. According to previous studies, hormonal therapy in these patients responded relatively well. Nevertheless, recurrence was not uncommon, accounting for 26.0% in AEH and 40.6% in EC. The standard treatment for these recurrent patients is hysterectomy, but if there is no myometrial invasion and no extrauterine lesions, repeated hormonal treatment can be considered. However, studies targeting these patients have been very scarce. The purpose of this study was to evaluate the efficacy and safety of high-dose progesterone therapy in recurrence following fertility preserving therapy for AEH or EEC. Methods: KGOG2031 is a multi-center and prospective phase 2 trial. The primary endpoint is a 2-year disease free survival. The secondary endpoints were duration of disease-free survival, overall survival, response rate, adverse events, and infertile rates. Patients with recurrent AEH or EEC without myometrial invasion or extrauterine lesions who underwent high-dose MPA therapy for primary lesions were included. The inclusion criteria are limited to patients with less than two recurrences. The pathologic type for EEC was confined to endometrioid type. The patients should be confirmed histologically at least one complete remission after first treatment. Patients with myometrial invasion, cervical involvement, or extrauterine lesions observed on abdominal/chest computed tomography or pelvic magnetic resonance imaging were excluded. Furthermore, grade 2 or 3 of endometrioid or any grade of other pathologic type of endometrial cancer or non-atypical endometrial hyperplasia were excluded. The enrolled patients should take medroxyprogesterone acetate 500mg every day. D&CB will be performed after anesthesia every 8 weeks to determine the effectiveness, and treatment will be continued for up to 40 weeks until complete remission is achieved. The target number of enrollment is 115 cases, and the recruitment period is 3 years. The follow-up duration is 2 years after the end of treatment, and the total study duration was up to 5 years. Citation Format: Min Kyu Kim, Yung-Taek Ouh. KGOG2031 A phase II trial of repeated high dose luteal hormone therapy for intrauterine recurrence following fertility preserving therapy for atypical endometrial hyperplasia or endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT044.