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Introduction/Background* In 2021, a joint ESGO/ESTRO/ESP committee updated their evidence-based guidelines for endometrial cancer, recommending a new risk grouping incorporating both clinicopathologic and molecular parameters. We applied the new risk grouping and compared the results to those of the prior 2016 clinicopathologic system. Methodology We classified molecularly a cohort of 604 women diagnosed with endometrial cancer using immunohistochemistry for TP53 and MMR proteins on a tissue microarray, as well as Sanger sequencing for POLE mutations. These results, combined with clinicopathologic data, allowed the patients to be risk grouped using both the new 2021 molecular/clinicopathologic parameters and the prior 2016 clinicopathologic system. Result(s)* The application of the 2021 molecular markers shows Kaplan-Meier curves with a significant difference between the groups for all survival. Molecular classification under the 2021 guidelines revealed a total of 39 patients (39/594, 7%) with a change in risk group in relation to the 2016 classification system: the shift was alone due to either P53abn or POLEmut molecular marker. In order to ensure correct 2021 molecular risk classification, not all patients with endometrial cancer need a molecular diagnostic: 433 (72.9%) cases would need to be analyzed by TP53 IHC, only 46 (7.7%) by MMR IHC and 286 (48.1%) POLE sequencing reactions. Conclusion* Application of the 2021 molecular risk groups is feasible and shows significant differences in survival. IHC for TP53 and MMR and applying POLE sequencing is only needed in selected cases and leads to shifting risk groups both upward and downward for a sizeable number of patients. It is possible to significantly reduce the number of analyses required to implement the classification if resources are limited.

Introduction/Background The role of lymphadenectomy in surgical staging for endometrial cancer remains controversial. The standard of care – consisting of a pelvic and para-aortic lymphadenectomy (LND) – has failed to show survival advantage while leading to an increased peri- and postoperative morbidity. Sentinel lymph node (SLN) mapping has gained popularity, offering a compromise between no nodal staging and complete LND. Multiple studies have demonstrated high detecection rates and negative predictive values of SLN mapping with near-infrared fluorescence imaging and indocyanine green (ICG) in endometrial cancer. However, the literature contains limited data on its safety and oncological outcomes. Aim of this study is to evaluate the oncological outcome of SLN mapping in patients with intermediate-risk endometrial cancer. Methodology In a retrospective, single-center study, we investigated the oncological outcome of patients with stage I intermediate-risk endometrial cancer who underwent surgical staging at our institution between February 2013 and July 2020. Results Out of a total number of 306 patients with endometrial cancer, 57 patients were diagnosed with node-negative intermediate-risk endometroid endometrial cancer (FIGO IA grade 3, FIGO IB grade 1 or 2). All patients were treated with laparoscopic hysterectomy and bilateral salpingo-oophorectomy with ICG SLN mapping. 31 patients additionally underwent comprehensive surgical staging (four systematic pelvic lymphadenectomies and 27 pelvic and para-aortic lymphadenectomies, LND group). Mean follow up time was 38.0 months. Adjuvant treatment consisted of vaginal brachytherapy in 49 patients, additional chemotherapy in four patients and no adjuvant treatment in eight patients. Between the two cohorts, there were no differences in age or BMI. The mean number of lymph nodes removed (4.04 vs. 45.5), the duration of the surgical procedure (131.3 vs. 287 minutes) as well as the intraoperative blood loss (101.9 vs. 258.1 ml) were significantly higher in the LND group (p=0.000, 0.000 and 0.026, respectively). Recurrence rates (7.7% SLN, 9.7% LND, p=0.585) and death due to disease (3.8% SLN, 3.2% LND, p=0.709) were similar between the two groups. Further on, there was no statistically significant difference in overall and recurrence free survival for patients with SLN mapping only compared to the LND cohort (p=0.541 and 0.480, respectively). Conclusion In our cohort, the use of ICG SLN mapping alone did not impair oncological outcome compared to a complete lymphadenectomy. It therefore might provide an efficient alternative of nodal staging with less morbidity in intermediate-risk endometrial cancer patients. However, prospective studies on larger numbers of patients are needed to confirm our findings. Disclosures No disclosures.