Dr. Barber on the Role of Molecular Profiling for Treatment Considerations in Endometrial Cancer

Emma L. Barber, MD, assistant professor, Gynecologic Oncology, the Northwestern University Feinberg School of Medicine, director, Robotic Surgery, the Division of Gynecologic Oncology, Northwestern Medicine, discusses the role of molecular profiling for treatment considerations in patients with endometrial cancer.

When a patient presents with endometrial cancer, the first step is to test for POLE mutations, since POLEmutations with an ultra-mutated phenotype are associated with a good prognosis, Barber begins. However, a patient’s histology and stage could take precedence over the presence of a POLE mutation in certain situations, Barber explains. For example, if patient with stage III endometrial cancer has a POLE mutation, chemotherapy could still be the preferred option. For patients with stage IB, grade 3 endometrial cancer, the current guidelines recommend vaginal brachytherapy or whole pelvic radiation; however, if a patient with stage IB, grade 3 harbors a POLE mutation, treatment could be de-escalated with vaginal brachytherapy, Barber notes. 

If a patient does not have a POLE mutation, molecular profiling could next be used to examine mismatch repair status. Patients with mismatch repair–deficient (dMMR) endometrial cancer have been shown to be more likely to respond to radiation therapy compared with chemotherapy, based on a reanalysis of data from the phase 3 PORTEC-3 trial (NCT004111380), Barber explains. Additionally, platinum-based chemotherapy remains the standard first-line therapy for patients with dMMR metastatic endometrial cancer; however, a clinical trial that adds a checkpoint inhibitor could be an options for some patients, and a single-agent checkpoint inhibitor could be considered if a patient is too sick to treat with chemotherapy, Barber notes.

After checking POLE and MMR status, copy number–high or P53 mutations could also affect treatment decisions. Although patients who are copy number–high or have P53 mutations tend to have a poorer prognosis, they may also respond better to chemotherapy, based on data from PORTEC-3, Barber notes. In patients with stage IB, grade 3 disease or isolated tumor cells in a sentinel lymph node with a P53 mutation, escalating care may be considered due to associations with a poorer prognosis, Barber concludes.