Cervical stromal invasion and molecular characterization in stage II-IV endometrial cancers

Objective: The optimal treatment for patients with cervical stromal invasion (CSI) in endometrial cancer (EC) remains unclear. We aimed to test the prognostic role of molecular classification in EC patients with CSI. Methods: A retrospective, multicenter review of EC patients with CSI was performed. EC cases were assigned to one of the molecular classes: POLE mutated (POLEmut), MMR deficient (MMRd), p53 abnormal (p53abn), or no specific molecular profile (NSMP). Three-year recurrence-free survival (RFS) from surgery was estimated using the Kaplan-Meier method. Cox proportional hazards regression models were fit to adjust for confounders. Results: Overall, 162 EC patients with CSI were identified: 70 (43.2 %) NSMP, 49 (30.2 %) p53abn, 40 (24.7 %) MMRd, 3 (1.9 %) POLEmut. POLEmut cases were excluded from further analysis, because of the small number of patients identified. At univariate analysis, molecular class was significantly associated with recurrence within 3 years after surgery (p = 0.04). Three-year RFS was 59.9 % (95 % confidence interval [CI], 46.1–77.8 %) for NSMP, 50.6 % (95 % CI, 34.9–73.2 %) for MMRd, and 33.1 % (95 % CI, 19.7–55.3 %) for p53abn. After adjusting for stage and grade, molecular class was no longer significantly associated with recurrence within three years (p = 0.28). Conclusions: Traditional risk factors such as grade and stage remain critical in determining the prognosis of endometrial cancer with cervical stromal invasion. This study highlights the importance of integrating both molecular and morphological features in determining the prognosis of endometrial cancer, with particular emphasis on endometrioid histotypes.