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Rapid Review: Endometrial Cancer

Rapid Review: Endometrial Cancer

Medscape18-07-2025
In endometrial cancer, the majority of cases are diagnosed at an early stage, largely due to the hallmark symptom of postmenopausal bleeding. Despite relatively favorable survival rates when caught early — with a 5-year relative survival rate of approximately 95% for localized disease — disparities remain in detection, treatment access, and mortality.
ctDNA testing has shown strong value as a noninvasive and highly sensitive method for detecting recurrence in endometrial cancer. ctDNA detects tumor-specific mutations in the bloodstream and is being actively evaluated to track cancer progression, detect early-stage cancers, and monitor therapeutic responses. ctDNA's role for detecting hormone receptor status and tumor histology has not been established for endometrial cancer, and it appears to not be correlated with myometrial invasion depth.
Learn more about the presentation of endometrial cancer.
In the past year, evidence has emerged which demonstrates that GLP-1 receptor agonists — medications originally approved for diabetes and obesity — reduce the risk for obesity-related cancers. A major research effort found that these drugs decreased cancer incidence, and further research found GLP-1 receptor agonists to be comparable to bariatric surgery for obesity-related cancer prevention. GLP-1 therapies now offer a less-invasive alternative to bariatric surgery. Research is ongoing to evaluate the use of GLP-1 medications as a potential therapeutic strategy for endometrial cancer. The other classes have not been shown to reduce risk or are not used in endometrial cancer management.
Learn more about the differential diagnosis for endometrial cancer.
Recent advances in molecular and genomic profiling have significantly refined the precision with which therapies can be selected for patients with endometrial cancer. These tools enable clinicians to pinpoint genetic and molecular characteristics that dictate tumor behavior and response to treatment, improving personalized treatment strategies and overall survival outcomes. Rather than uniformly applying treatments, clinicians have the ability to tailor therapies based on individual molecular profiles. Adjuvant therapy may still be warranted depending on the risk associated with the molecular/genomic subtypes identified, and best practice histopathology evaluation is still needed even when advanced profiling is done.
Further research continues to expand the depth and breadth of genomic profiling, making it a crucial element of modern oncology practice.
Learn more about the workup for endometrial cancer.
The TCGA molecular classification divides endometrial cancers into four biologically distinct subtypes: POLE-ultramutated, MSI-H, copy number-low (endometrioid), and copy number-high (serous-like). These molecular profiles provide prognostic insights and increasingly guide therapeutic strategies beyond traditional histology and staging. For example, POLE-mutated tumors, despite high mutation burdens, have excellent outcomes and may not require aggressive adjuvant therapy. In contrast, copy number-high tumors are associated with poor prognosis and may benefit from more intensive treatment and HER2-targeted therapies. This classification is part of a shift toward personalized medicine in gynecologic oncology.
Learn more about guidelines for endometrial cancer.
Compared to traditional open surgery, MIS dramatically shortens hospital stays, decreases blood loss, and has fewer overall complications, although it does lengthen operation time. Furthermore, minimally invasive approaches maintain oncologic outcomes comparable to those of traditional open surgery, providing reassurance regarding their safety and efficacy. Because endometrial cancer patients often have obesity, MIS has the potential to reduce the risk for postoperative wound complications. It also is likely to decrease other postoperative morbidities by supporting faster recovery and earlier resumption of normal daily activities. Additionally, lymph node assessment may still be needed after MIS.
Learn more about risk assessment in patients with endometrial cancer.
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