Deep cervical stromal invasion predicts poor prognosis in endometrioid endometrial cancer with cervical stromal involvement: a risk-stratification model for adjuvant therapy decision-making in endometrial carcinoma.

Background: Endometrioid endometrial cancer with cervical stromal invasion (CSI) has heterogeneous prognoses, but current models inadequately incorporate CSI depth. We evaluated whether deep CSI (≥50% stromal thickness) predicts poor prognosis and developed a risk-stratification model integrating molecular classification to guide adjuvant therapy. Methods: We conducted a single-center retrospective cohort study of 412 patients with endometrioid endometrial cancer with cervical stromal invasion treated between January 2021 and January 2023. CSI depth was categorized as deep (≥50%) versus superficial (<50%) based on standardized pathological review. Molecular subtyping was performed per 2023 FIGO criteria. The primary endpoint was 3-year recurrence-free survival (RFS). Multivariable Cox regression identified independent prognostic factors. A weighted four-factor risk score was developed incorporating deep CSI (2 points), G3 histology (1 point), substantial lymphovascular space invasion (LVSI, 1 point), and p53-aberrant subtype (1 point). Propensity score-matched analysis (1:1 matching) evaluated external beam radiotherapy (EBRT) efficacy in deep CSI patients. Results: Deep CSI was present in 71 patients (17.2%) and was associated with aggressive pathological features: higher grade (G3: 35.2% vs. 18.5%, Conclusions: Deep CSI provides critical prognostic information in endometrioid endometrial cancer. Integration of CSI depth with molecular classification enables actionable risk stratification and identifies patients who benefit from EBRT.