Endometrial cancer staging is a critical aspect of managing endometrial cancer, as it helps to determine the extent of disease and a patient’s prognosis, ultimately guiding treatment decisions. At the recent Society of Gynecologic Oncology (SGO) 2025 Annual Meeting on Women’s Cancer, researchers highlighted how staging has been evolving since the integration of molecular profiling.

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Following these presentations, featured expert Alexander B. Olawaiye, MD, FRCOG, FACOG, FACS, was interviewed by Conference Reporter Medical Director Lauren Weinand, MD. Dr Olawaiye’s clinical perspectives on these findings are presented here.

The primary staging approach for endometrial cancer is surgical because the purpose of staging is to define the extent of disease. We are then able to triage patients for adjuvant therapy, including adjuvant systemic therapy, such as chemotherapy, immunotherapy, and targeted therapy, and, sometimes, adjuvant radiotherapy or other treatments. When surgical staging is not feasible in, for example, patients who are unable to undergo surgery, we may stage them based on clinical examination and imaging findings. Three-dimensional imaging modalities are used to get a sense of disease distribution. There is also a molecular classification of endometrial cancer based on The Cancer Genome Atlas (TCGA) program publication, which divides endometrial cancers into 4 separate groups. So, we have surgical and clinical staging and molecular classification.

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At the SGO 2025 Annual Meeting on Women’s Cancer, a study presented by Allison Roy, MD, and colleagues used a large data set to evaluate the impact of the 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system on early-stage endometrial cancer (poster 204). Credit has to be given to FIGO for revising endometrial cancer staging and incorporating molecular classification into the most recently updated staging system. However, the study by Roy et al reported that the 2023 FIGO staging system may result in overtreatment compared with the 2009 FIGO staging system. The adoption of the FIGO staging system is not universal, and this study probably indirectly speaks to the areas of significant concern behind this.

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It is important to note that if you have any ability or opportunity to perform molecular classification on the cancer tissue from your patients with endometrial cancer, you must take that opportunity. A 2013 publication clearly showed that some endometrial cancers are wolves in sheep’s clothing molecularly and may be more aggressive than they appear histologically. Conversely, other endometrial cancers are sheep in wolf’s clothing and may look aggressive, but they are not.

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As mentioned previously, the TCGA molecular classification divides endometrial cancer into the following 4 categories: POLE-ultramutated, microsatellite instability–hypermutated (MSI-H)/mismatch repair–deficient (dMMR), copy number–low/nonspecific molecular profile, and copy number–high/serous-like endometrial cancer. The POLE-ultramutated group has the best prognosis but only represented 7% of endometrial cancers in the study. The MSI-H/dMMR and the copy number–low/nonspecific molecular profile groups have an intermediate prognosis, and the copy number–high/serous-like group has the worst prognosis.

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A study presented by Oleksandra Dzyubak, MD, and colleagues at the SGO meeting evaluated whether there is sufficient evidence to tailor lymph node staging based on a person’s molecular status (poster 230). The idea is that you could potentially de-escalate the surgical intensity in the group of patients with POLE-ultramutated endometrial cancer, for example, and reserve it for those who have intermediate- to high-risk tumors. However, this presupposes that you can obtain the molecular profile of the tumor before surgery, which is a monumental task for many—if not most—people. At some institutions, this may be doable and potentially even easy, but, at most institutions, this is difficult, as most institutions are not in the position of being able to do it. The authors concluded that there is insufficient evidence to tailor lymph node staging based on molecular status. We need robust data and feasibility assessments before we can make that kind of huge change.