Molecular Stratification and Surgical Management of Endometrial Cancer: Advances and Challenges

Endometrial cancer represents the most prevalent gynecologic malignancy in high-income regions, where its management conventionally hinges on clinicopathologic risk factors to define surgical strategy. The landscape has shifted in recent years with the advent of molecular classification systems, which offer improved prognostic capability and have begun to inform treatment algorithms, particularly regarding adjuvant therapies. This molecular revolution, however, has only partially permeated surgical decision-making, creating a gap between risk stratification and individualized patient management. Accumulating evidence suggests that molecular profiling—especially when available preoperatively—holds the potential to tailor the extent and nature of surgical interventions, such as the extent of hysterectomy, lymph node evaluation, and eligibility for fertility-sparing procedures. Despite these advancements, the practical integration of molecular data into routine surgical planning remains inconsistent, hampered by variations in clinical adoption, unresolved debates, and evolving guidelines.This Research Topic aims to bridge the divide between molecular stratification and evidence-based surgical management in endometrial cancer. The central objective is to clarify how molecular data, when coupled with clinical assessment and imaging, can inform and optimize operative approaches, minimize overtreatment, and reduce surgical morbidity. We seek to advance the conversation from theoretical promise to clinical application by examining how preoperative molecular testing may influence surgical extent, guide lymph node staging strategies (including sentinel node mapping), and support personalized, fertility-sparing management for select patient populations. The ultimate goal is to develop a practical, multidisciplinary roadmap that enables surgeons and care teams to operationalize molecular insights and meet the demands of precision medicine in everyday practice.This Research Topic is focused on the surgical application of molecular risk profiling in endometrial cancer management, emphasizing the translation of molecular, pathological, and clinical information into actionable surgical pathways. Submissions should provide a clear link to surgical planning, intraoperative decision-making, or postoperative outcomes, integrating molecular insights with multidisciplinary perspectives. To gather further insights, we welcome articles addressing, but not limited to, the following themes:o Preoperative molecular classification from biopsy and its impact on surgical planning;o Tailoring the extent of primary surgery according to molecular risk;o Lymph node assessment (including sentinel node mapping) in the molecular era;o Integration of molecular data with imaging and clinicopathologic factors;o Molecular profiling in fertility-sparing and less invasive management strategies;o Practical challenges, controversies, and evolving guidelines in molecularly informed surgery;o Translational and clinical studies linking molecular subtype to surgical outcomes.We invite the submission of original research articles, systematic and narrative reviews, meta-analyses, clinical trial reports, and expert opinions with clear relevance to surgical decision-making. Both translational and clinical studies are encouraged, provided they offer practical insights into the implementation, limitations, and future perspectives of molecularly guided surgical management in endometrial cancer. Topic editors: Matteo Marchetti, Marco Noventa, Matteo Loverro Source: https://www.frontiersin.org/research-topics/76918/molecular-stratification-and-surgical-management-of-endometrial-cancer-advances-and-challenges