Minimal Residual Disease Detection: Bridging Molecular and Clinical Strategies for Recurrence Prevention in Gynecologic Cancers.

Gynecologic cancers remain a major global health burden, particularly in low- and middle-income countries, with high incidence and mortality rates around 45-50%. The detection of minimal residual disease (MRD) is transforming the management of recurrence risk in gynecologic cancers through highly sensitive molecular technologies. MRD encompasses small populations of residual cancer cells or post-treatment molecular traces but remain undetectable by conventional methods. Its detection relies on circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and advanced next-generation sequencing (NGS), with ctDNA-based MRD assays having sensitivity levels between 85% and over 99%. Other technologies, such as liquid biopsies and digital PCR, are also in development. MRD status has demonstrated high predictors of recurrence and survival with positive MRD strongly associated with poor outcomes and negative MRD indicates sustained remission. However, MRD detection faces significant limitations, such as tumor heterogeneity, inconstant ctDNA levels, technical issues of false-negative results, and limited clinical accessibility. Therefore, this review presents current evidence regarding the molecular detection of MRD in gynecologic malignancies and assesses its prognostic and predictive relevance. Ultimately, MRD continuous integration into clinical practice offers a promising modality to enable early relapse detection, more precise therapeutic decision-making, and the improvement of personalized medicine access to gynecologic cancers worldwide.