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Life sciences · Journal article
Frontiers in Medicine · September 16, 2026
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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%, P = 0.003), deeper myometrial invasion (≥50%: 67.6% vs. 34.9%, P < 0.001), and substantial LVSI (33.8% vs. 12.9%, P = 0.002). Deep CSI independently predicted 3-year recurrence (adjusted HR 2.45, 95% CI 1.52–3.95, P < 0.001) after adjusting for molecular subtype and adjuvant therapy. The three-tier risk stratification identified distinct prognostic groups: low risk (0 points, n = 198, 48.1%): 3-year RFS 91.2%; intermediate risk (1–2 points, n = 163, 39.6%): 79.4%; high risk (3–5 points, n = 51, 12.4%): 52.8% ( P < 0.001). In propensity score-matched analysis, EBRT significantly improved 3-year RFS in deep CSI patients (78.6% vs. 48.2%, P = 0.012; HR 0.42, 95% CI 0.20–0.88), with particular benefit for locoregional control (89.3% vs. 62.5%, P = 0.008). The prognostic impact of deep CSI varied by molecular subtype: no significant effect in polymerase epsilon (POLE)-mutated, mismatch repair deficient (MMRd) tumors, but identified high-risk subsets within no specific molecular profile (NSMP) tumors. 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.