Abstract
Liquid biopsy offers a noninvasive method to identify and monitor tumor-derived biomarkers, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, microRNAs, and tumor-educated platelets, that provide real-time insights into the biological behavior of gynecological cancers. The detection of these markers has the potential to revolutionize cancer management by enabling earlier detection, providing novel data to personalize treatments, and predicting disease recurrence before clinical imaging and predicting disease recurrence before clinical imaging can confirm progression, thereby also guiding complex clinical decision-making. However, because this new "omics" layer introduces additional complexity, it must be fully understood, from its biological rationale to technical development and clinical integration, to prevent confusion or misapplication. That is why, focusing on 14 critical fields of inquiry, our goal is to map the current state of liquid biopsy from bench to bedside while highlighting practical considerations for clinical integration. Each topic integrates recent advances in assay sensitivity, biomarker variability, and data interpretation, underscoring how standardized protocols and robust analytical methods are pivotal for reliable results. We then translate these findings into disease-specific insights, examining how liquid biopsy could refine early detection, minimal residual disease assessment, and therapy guidance in endometrial, cervical, and ovarian cancers. Although several FDA-approved assays and promising commercial tests illustrate the field's rapid evolution, many translational hurdles remain, including the need for harmonized protocols, larger prospective clinical trials, and cost-effectiveness analyses. Crucially, our synthesis clarifies the pivotal role of interdisciplinary collaboration. Oncologists, laboratory scientists, and industry partners must align on standardized procedures and clinically relevant endpoints. Without such coordination, promising biomarkers may remain confined to research settings, limiting their practical benefit. Taken together, our review offers a translational view designed to contextualize liquid biopsy in gynecological oncology.