Adjuvant radiotherapy for early-stage endometrial cancer based on randomized controlled trials: a narrative review

Endometrial carcinoma (EC) is the most common gynecologic malignancy in the USA, with surgical staging as the cornerstone of treatment. Although most patients are diagnosed at an early stage, adjuvant therapies, including external beam radiation therapy (EBRT), vaginal brachytherapy (VBT), and systemic treatments, are employed in select cases to reduce recurrence risk. This review highlights data from randomized controlled trials assessing the efficacy of adjuvant radiotherapy in early-stage EC. For low-risk EC, studies suggest that postoperative brachytherapy has minimal impact on locoregional recurrence and is not recommended without significant uterine risk factors. In intermediate-risk EC, trials such as GOG 99 and PORTEC-1 demonstrated reduced recurrence with pelvic RT, particularly in high-intermediate risk subsets, though overall survival benefits were not observed. For high-intermediate risk EC, PORTEC-2 showed that VBT effectively controls vaginal recurrence with less morbidity compared to EBRT, recommending VBT as the preferred modality. Medium-risk cases benefit similarly from VBT alone, as shown in Swedish trials. In high-risk EC, RCTs such as GOG 249 and PORTEC-3 examined the addition of chemotherapy to radiotherapy, finding comparable recurrence and survival outcomes between VBT with chemotherapy and EBRT, though acute toxicity was higher with combined therapy. Across these trials, the degree of lymphovascular space invasion (LVSI), patient age, tumor grade, and histology were key prognostic factors influencing treatment recommendations. Despite advancements in molecular classification and modern radiotherapy techniques, most data derive from earlier studies, emphasizing the need for updated research to refine treatment paradigms.