Sentinel node–positive POLE-mutated endometrial cancer

The molecular classification of endometrial cancer has revolutionized risk stratification, with POLE-mutated tumors recognized for their excellent prognosis. However, the optimal management of patients with nodal involvement remains unclear. This multi-center retrospective study evaluates the outcomes of patients with stage IIIC endometrial cancer with positive sentinel lymph nodes harboring POLE mutations. Of 164 POLE-mutated cases undergoing sentinel node mapping, 11 (6.7%) had nodal metastases (classified as isolated tumor cells [n = 6; 54.5%], micro-metastases [n = 3; 27.3%], or macro-metastases [n = 2; 18.2%]). All patients except 1 received adjuvant therapy, tailored according to molecular and pathologic risk factors. After a median follow-up of 7.6 months, no recurrences were observed. These findings suggest excellent short-term outcomes, even in node-positive POLE-mutated endometrial cancer. Nevertheless, the study does not support omitting adjuvant therapy in this setting. Larger studies and long-term data, such as those expected from the ongoing Refining Adjuvant treatment IN endometrial cancer Based On molecular features (RAINBO)/ Blue trial are needed to guide safe de-escalation strategies.