Genetic Twist in Endometrial Cancer

Introduction: Identifying mutations in the POLE gene in endometrial cancer has direct implications for therapeutic management, potentially allowing clinicians to avoid aggressive adjuvant treatments in patients with a favorable molecular profile. Endometrial cancer is the most common gynecological neoplasm in developed countries, with a predominance of the endometrioid subtype. Recently, the molecular classification proposed by The Cancer Genome Atlas identified four distinct subtypes, including the group with POLE gene mutations, characterized by ultramutation, excellent prognosis, and low recurrence rates. Methods: A clinical case study involved a 58-year-old with high-grade endometrioid adenocarcinoma, stage IB. The patient underwent total hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy. Genetic sequencing of the tumor confirmed the POLE mutation. The therapeutic approach was discussed at a multidisciplinary meeting, considering clinical, histopathological, and molecular data. The team decided to proceed with observation without adjuvant therapy. The patient experienced a favorable outcome post-operatively, with no evidence of disease recurrence at follow-up. Results: The POLE mutation is associated with a robust tumor immune response and excellent overall survival, even in high-grade tumors. Several studies, including ESGO/ESTRO/ESMO guidelines, recommend that patients with this molecular profile be treated with surgery alone, without the need for radiotherapy or adjuvant chemotherapy, provided there are no high-risk clinical factors. In the case analyzed, the patient had a satisfactory surgical recovery without complications. Conclusions: The molecular characterization of endometrial cancer, especially the identification of the POLE mutation, represents a significant advance in personalized treatment. In patients with this profile, such as the 58-year-old woman analyzed, a surgical approach alone may be sufficient, avoiding unnecessary toxicities and maintaining an excellent prognosis. The incorporation of genomics into clinical practice reinforces the importance of precision medicine in gynecological oncology.