High-Risk Early-Stage Endometrial Cancer: Role of Adjuvant Therapy and Prognostic Factors Affecting Survival

<b>Background/Objectives:</b> High-grade endometrial cancer, including non-endometrioid and grade 3 endometrioid histologies, is associated with poor prognosis despite early-stage diagnosis. This study assessed the prognosis of early-stage high-grade endometrial cancer, identified prognostic factors, and evaluated the optimal candidates for adjuvant therapy. <b>Methods:</b> We retrospectively analyzed 106 patients with 2018 FIGO stage I-II high-grade endometrial cancer who underwent hysterectomies between 2008 and 2022. Adjuvant therapy was determined by a multidisciplinary team. Survival outcomes were evaluated using the Kaplan-Meier method and Cox regression model. <b>Results:</b> Of 106 patients, 60 had non-endometrioid, and 46 had grade 3 endometrioid carcinoma; 69 (65.1%) received adjuvant therapy. After a median follow-up of 48.8 months, 37 patients experienced disease progression, and 21 died. Non-endometrioid histology was significantly associated with worse overall survival (<i>p</i> = 0.002). Lack of lymph node dissection, deeper invasion, and the omission of adjuvant therapy were additional adverse prognostic factors. Adjuvant therapy improved the overall survival (<i>p</i> = 0.009), disease-free survival (<i>p</i> = 0.021), and locoregional recurrence-free survival (<i>p</i> = 0.034) in patients with one or two risk factors. <b>Conclusions:</b> Non-endometrioid histology, deep invasion, and the lack of lymph node dissection are associated with worse survival in early-stage high-grade endometrial cancer. Adjuvant therapy should be considered in patients with these risk factors.