SGO Clinical Practice Committee Publishes Statement “Molecular testing for endometrial cancer”

The SGO Clinical Practice Committee recently published, “Molecular testing for endometrial cancer: An SGO clinical practice statement,” a report intended to guide appropriate testing, interpretation, and application of molecular information in endometrial cancer. The practice statement appears in the January issue of Gynecologic Oncology.

The Cancer Genome Atlas (TCGA) and the ProMisE algorithms classify endometrial cancers into four different subgroups based on POLE, mismatch repair deficiency (MMR-D), and P53 status. When it comes to how these algorithms are being utilized in practice, Christine Walsh, MD, and Kari Hacker, MD, explain, “We are using MMR-D status to make treatment decisions in recurrent and metastatic endometrial cancer and using a testing algorithm to identify patients who should undergo genetic testing for Lynch Syndrome.”

The question of who should undergo evaluation is met with the suggestion that all patients should be tested at initial diagnosis to observe loss of expression and to inform the need for genetic testing. The importance of molecular testing is the information provided to make second line treatment decisions. In other words, the course of action following chemotherapy for recurrent and metastatic endometrial cancer can lean heavily on the results of specialized classification.

According to Drs. Walsh and Hacker, biomarkers serve the following purposes:

• MMR-D, MSI, and TMB-H status are used to choose FDA-approved therapy options.
• HER2, P53, and hormone receptor status are predictive biomarkers for response to therapy.
• L1CAM, CTNNB1, POLE, and PD-L1 are prognostic and ARID1A, PI3K, AKT, and mTOR are exploratory biomarkers.
• HER2 amplification makes a patient eligible for the addition of trastuzumab to chemotherapy in patients with advanced or recurrent uterine serous carcinoma.

There are many ongoing clinical trials evaluating the effect of using molecular biomarker information to determine the need for treatment firstly and then the required nature of treatment secondly. Dr. Walsh identifies several of these trials noting, “In newly diagnosed endometrial cancer, the PORTEC-4a, RAINBO and NRG-GY010 trials are evaluating different adjuvant therapy strategies based on TCGA/ProMisE classifications, other biomarkers, and uterine risk factors. In recurrent and metastatic endometrial cancer, the KEYNOTE-C93, NRG-GY025, EndoMAP, and PODIUM-204 trials are evaluating different systemic therapy combinations for different biomarker-based groups.” The hope of these ongoing clinical trials is that the results will yield better future understanding of how to incorporate biomarker testing into treatment decision making with the ultimate goal of improving outcomes for patients.