Liquid Biopsy Biomarkers in Endometrial Cancer: Current Landscape and Future Perspectives
Walter Giuseppe Giordano, Ludovica Pepe, Canio Martinelli, Valeria Zuccalà, Giuliana Ciappina, Massimiliano Berretta, Giuseppe Giuffrè, Vincenzo Fiorentino, Antonio IeniEndometrial cancer is the most common gynecologic malignancy in developed countries and remains challenging in terms of risk stratification, treatment monitoring, and early detection of recurrence. Liquid biopsy provides a minimally invasive approach for the dynamic assessment of tumor-derived biomarkers and may complement tissue-based diagnosis and molecular classification. This narrative review summarizes current evidence on circulating biomarkers in endometrial cancer, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), extracellular vesicles (EVs), circulating microRNAs, and tumor-educated platelets, with attention to validity, applicability, and implementation barriers. Among these biomarkers, ctDNA currently has the strongest evidence base, especially for longitudinal monitoring, prognostic stratification, molecular residual disease assessment, and early detection of relapse in high-risk or recurrent disease. However, its sensitivity remains limited in early-stage, low-volume, and low-shedding tumors. CTCs, EVs, microRNAs, and platelet-derived signatures are promising but still largely investigational. Artificial intelligence may support multimodal biomarker validation, although clinical adoption will require external validation, locked algorithms, standardized workflows, and prospective utility trials. Overall, liquid biopsy represents a promising adjunct to tissue-based diagnosis and molecular classification in endometrial cancer, particularly for monitoring and follow-up. Prospective studies are now needed to demonstrate whether liquid-biopsy-informed decisions can improve outcomes or safely reduce overtreatment.