The DaPHNE study is an observational, ambispective, multicenter study designed to evaluate whether the integration of circulating tumor DNA (ctDNA) and plasma proteomic profiling with the 2023 FIGO staging system improves prognostic stratification in patients with endometrial cancer (EC) treated with curative-intent surgery. The study will compare the prognostic performance of the standard FIGO 2023 staging system with an enhanced longitudinal staging approach (L-FIGO 2023) incorporating preoperative (T0) and postoperative (T1, 4-6 weeks after surgery) liquid biopsy data, and will explore a dynamic model (Δ-FIGO) based on changes between these time points.

The study consists of two phases: (1) a retrospective cohort including approximately 300 patients with stored plasma samples and clinical data, and (2) a prospective cohort of 100 newly enrolled patients from participating centers. Plasma samples will undergo ctDNA sequencing, methylation analysis, and proteomic profiling using next-generation sequencing and Olink technologies. Molecular findings will be integrated with clinicopathological and survival data to identify biomarkers associated with minimal residual disease, recurrence, and progression-free survival, validate multimodal prognostic models across institutions, assess concordance between circulating and tissue biomarkers, and identify molecular pathways relevant for personalized treatment strategies. The primary endpoint is progression-free survival.