{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:04:48Z","timestamp":1789538688151,"version":"build-2803163510"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Endometrioid endometrial cancer with cervical stromal invasion (CSI) has heterogeneous prognoses, but current models inadequately incorporate CSI depth. We evaluated whether deep CSI (\u226550% stromal thickness) predicts poor prognosis and developed a risk-stratification model integrating molecular classification to guide adjuvant therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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 (\u226550%) versus superficial (&amp;lt;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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Deep CSI was present in 71 patients (17.2%) and was associated with aggressive pathological features: higher grade (G3: 35.2% vs. 18.5%,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.003), deeper myometrial invasion (\u226550%: 67.6% vs. 34.9%,\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001), and substantial LVSI (33.8% vs. 12.9%,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.002). Deep CSI independently predicted 3-year recurrence (adjusted HR 2.45, 95% CI 1.52\u20133.95,\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001) after adjusting for molecular subtype and adjuvant therapy. The three-tier risk stratification identified distinct prognostic groups: low risk (0 points,\n                      <jats:italic>n<\/jats:italic>\n                      = 198, 48.1%): 3-year RFS 91.2%; intermediate risk (1\u20132 points,\n                      <jats:italic>n<\/jats:italic>\n                      = 163, 39.6%): 79.4%; high risk (3\u20135 points,\n                      <jats:italic>n<\/jats:italic>\n                      = 51, 12.4%): 52.8% (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001). In propensity score-matched analysis, EBRT significantly improved 3-year RFS in deep CSI patients (78.6% vs. 48.2%,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.012; HR 0.42, 95% CI 0.20\u20130.88), with particular benefit for locoregional control (89.3% vs. 62.5%,\n                      <jats:italic>P<\/jats:italic>\n                      = 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1851729","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:31:54Z","timestamp":1789536714000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["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"],"prefix":"10.3389","volume":"13","author":[{"given":"Yanjiao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Gynecology, Anxi County Hospital","place":["Quanzhou, China"]},{"name":"Sun Yat-sen University Cancer Center","place":["Guangzhou, 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