Study case flow diagram for WES of translational specimens from patients enrolled in GOG281. One hundred thirty-four samples underwent successful WES, of which 112 were also evaluable for pERK via IHC. Additionally, 36 samples were evaluable for pERK IHC that did not have matching WES.

Purpose: Low-grade serous ovarian carcinoma (LGSOC) is a distinct form of ovarian cancer characterized by younger patient age and relative chemoresistance. The GOG281/LOGS trial (NCT02101788) investigated the efficacy of the MEK inhibitor trametinib compared with physician's choice standard-of-care (SOC) in patients with LGSOC with persistent/recurrent disease. The study demonstrated significantly improved progression-free survival (PFS) in the trametinib-treated arm. Experimental Design: Two hundred and sixty patients with recurrent/persistent LGSOC were enrolled and randomly assigned in GOG281. We performed molecular analysis of 170 patients with available tumor specimens, comprising whole-exome sequencing and phospho-ERK (pERK) IHC, to identify biomarkers of clinical benefit from trametinib. The demographics of the translational cohort (n = 170) were comparable with those of the total trial cohort. Results: High tumor pERK expression (greater than the median histoscore of 140) was associated with significantly prolonged PFS with trametinib treatment versus SOC (median 20.1 vs. 5.6 months, log-rank P < 0.0001; test for interaction P = 0.023). Tumors harboring canonical RAS-RAF-MAPK mutations (KRAS/BRAF/NRAS: 44/134, 32.8% of cases) had a higher response rate to trametinib (50.0% vs. 8.3%; Barnard's P = 0.0004; test for interaction P = 0.054), but KRAS/BRAF/NRAS status was not predictive of prolonged PFS (test for interaction P = 0.719). KRAS amplification (n = 5 without KRAS/NRAS/BRAF mutation) and mutation of MAPK-associated genes (n = 25 without KRAS/NRAS/BRAF mutation or KRAS copy number gain) expanded the number of cases with identifiable MAPK defects to 55.2%, but consideration of these events did not improve the discrimination of trametinib responders. Chr1p loss (49% of cases) was associated with lower pERK expression (P = 0.021). Conclusions: This exploratory analysis suggests that pERK expression and mutation of KRAS/BRAF/NRAS are candidate biomarkers of improved PFS and response to trametinib, respectively.

OBJECTIVE:Dostarlimab+carboplatin-paclitaxel (CP) demonstrated significant improvement in progression-free survival (PFS) and clinically meaningful improvement in overall survival (OS) vs CP alone among patients with dMMR/MSI-H primary advanced/recurrent endometrial cancer (EC) in Part 1 of the randomized phase 3 RUBY trial (NCT03981796). We report updated efficacy and safety data with approximately 4 years of follow-up. METHODS:Patients were randomized 1:1 to receive dostarlimab+CP or placebo+CP followed by dostarlimab or placebo up to 3 years or until disease progression. Descriptive analyses of OS and PFS were conducted in the dMMR/MSI-H population (median follow-up, 55.6 months). Post hoc conditional survival analyses and a mixture cure model (MCM) fitted to PFS data to estimate the proportion of patients who had curative potential are presented to provide prognostic insights into long-term survival. RESULTS:Dostarlimab+CP demonstrated sustained OS and PFS benefits. Median PFS and OS were not reached with a 66% reduction in risk of death vs placebo+CP. PFS curve plateauing (only 4 progression events with additional 2.5 years follow-up since the previous PFS analysis at interim analysis 1) demonstrated durable disease control. Patients alive at the 1- and 2-year landmarks had >80% probability of remaining alive an additional 3 and 2 years, respectively. At 4 years, the MCM analysis estimated a cure rate with dostarlimab of 54% (95% CI 35%-72%). No new safety signals were observed. CONCLUSIONS:At 4 years, RUBY demonstrated sustained remission and long-term survival benefit, suggesting the potential for curative intent with dostarlimab+CP in patients with dMMR/MSI-H primary advanced or recurrent EC.

Impact of pERK status and KRAS/BRAF/NRAS mutation status on GOG281 patient outcome. A, PFS of GOG281/LOGS patients with low-pERK tumors (pERK ≤ 140) in trametinib versus SOC arms. B, PFS of GOG281/LOGS patients with high-pERK tumors (pERK > 140) in trametinib versus SOC arms. C, PFS of GOG281/LOGS patients with KRAS/BRAF/NRAS WT tumors in trametinib versus SOC arms. D, PFS of GOG281/LOGS patients with KRAS/BRAF/NRAS-mutant tumors in trametinib versus SOC arms. Labeled HR refer to comparison of trametinib versus SOC arm.

Abstract Background: In RUBY Part 1 (NCT03981796), dostarlimab + carboplatin-paclitaxel (D+CP) significantly improved PFS and OS vs CP alone in pts with primary advanced or recurrent endometrial cancer (EC). Although MMR deficiency (dMMR) is a predictive biomarker for clinical response, benefit is also observed in the MMR proficient (MMRp) subgroup. Additional insights into the underlying biology and heterogeneity of these tumors are needed to inform potential drivers of response to D+CP. Methods: RNA sequencing (RNASeq) and whole exome sequencing were performed on 400 tumor samples from RUBY Part 1. Tumors were categorized as dMMR or MMRp per the testing method used for study enrollment. Genomic alterations and RNAseq signatures associated with infiltrating cell types or oncogenic processes were analyzed. Results: Unsupervised clustering of tumor transcriptional profiles revealed two distinct histological subtype-associated clusters. dMMR tumors were predominantly in the endometrioid cluster; MMRp tumors were distributed across both clusters. Gene signature analysis revealed significant enrichment for tumors with high immune cell signature scores in the dMMR subgroup (Table); however, considerable overlap was observed with a subset of MMRp tumors demonstrating similarly high signature scores. Conversely, signatures associated with tumor senescence and interferon-stimulated genes were enriched in the MMRp subgroup. Genomic analysis revealed frequent alterations in TP53, PTEN, PIK3CA, and ARID1A, with higher mutation rates of several genes (eg, JAK1 and RNF43) observed in dMMR tumors, concomitant with higher tumor mutational burden. Conclusions: These results highlight the molecular and transcriptomic heterogeneity of EC, providing hypotheses to explore the impact of tumor characteristics beyond MMR status on response to dostarlimab+CP in EC. Exploration of the association between these biomarkers and outcomes is ongoing. Citation Format: Lucy Gilbert, Annika Auranen, Mitchell I. Edelson, Mikalai Pishchyk, Joseph Buscema, Tamar Safra, Nicole S. Nevadunsky, Christine Gennigens, Kari Ring, Line Bjørge, Bhavana Pothuri, Helen D. Eshed, Iwona Podzielinski, Noelle G. Cloven, Tashanna K. Myers, Kathryn P. Pennington, Claire Rooney, Rumen Kostadinov, Robert W. Holloway, Trine Nøttrup. Heterogeneity in tumor microenvironment across MMR subtypes of endometrial cancer: Analysis from the ENGOT-EN6-NSGO/GOG-3031/RUBY trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3881.

Demographics of translational research population.

Unsupervised hierarchical clustering of chromosome arm-level copy-number alterations across biospecimens from patients enrolled in GOG281/LOGS.

Molecular landscape of tumor samples from patients enrolled in GOG281/LOGS. MAPK-associated, MAPK-associated genes as defined in the Gene Ontology Term GO:0000165; Chr1pq-aberrant, chr1p-loss with concurrent chr1q-gain.

pERK and other potential biomarkers of therapy response in LGSOC. A, pERK IHC examples demonstrating negative (0), weak (1+), moderate (2+), and intense (3+) positivity for histoscore calculation. Scale bars, 50 µm. B, Response to trametinib (top) and physician’s choice SOC (bottom) according to KRAS/BRAF/NRAS mutation status (left), pERK status (middle), and chr1 abnormalities (right). C, pERK histoscore according to KRAS/BRAF/NRAS mutation type. Labels specify the numbers within each group that were evaluable for pERK expression levels. D, pERK histoscore by chr1p-loss status. E, Frequency of pERK status between chr1p-loss and -intact groups. Chr1pq-aberrant, chr1p-loss with concurrent chr1q-gain.

INTRODUCTION:We evaluated the efficacy of the addition of the anti-diabetic drug metformin to standard-of-care paclitaxel and carboplatin (PC) in patients with advanced and recurrent endometrial cancer (EC). METHODS:In this phase II/III trial, EC patients with chemotherapy-naïve stage III/IVA (with measurable disease) and stage IVB or recurrent (with or without measurable disease) disease were randomly assigned to PC/metformin (850 mg BID) versus PC/placebo. Metformin or placebo was continued as maintenance therapy after completion of PC until disease progression. The primary endpoint of phase II was progression-free survival (PFS). The primary endpoint of phase III was overall survival (OS). Secondary endpoints were objective response, duration of response, and toxicity. RESULTS:From 3/17/2014 to 12/22/2017, 448 patients were randomized to phase II/III studies, and the data were frozen for interim analysis. The phase II study deemed metformin worthy of further investigation in the phase III study. The interim phase III analysis stopped accrual for futility on 2/1/2018. The addition of metformin to PC had a slightly higher hazard of death compared to the PC regimen (HR = 1.088; 90% CI 0.803 to 1.475), which was sufficient to close the study early. The PFS had (HR = 0.814; 90% CI 0.635 to 1.043). At a median follow-up of 10 months and 121 deaths, median OS was not determined and 28 months, on PC/placebo and PC/metformin, respectively. CONCLUSION:The hazard ratios for PFS and OS endpoints was not sufficiently decreased with the addition of metformin to PC to justify continuing the trial.

(Abstracted from J Clin Oncol 2025;43(7):868–891 Diagnosis and treatment of ovarian cancer are challenging due to the lack of effective screening tools for advanced stages of disease. Advanced ovarian cancer, classified as the International Federation of Gynecology and Obstetrics stage III or IV, is traditionally treated with primary cytoreductive surgery (PCS) followed by chemotherapy.

PURPOSE:To provide updated guidance regarding neoadjuvant chemotherapy (NACT) and primary cytoreductive surgery (PCS) among patients with stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer (epithelial ovarian cancer [EOC]). METHODS:A multidisciplinary Expert Panel convened and updated the systematic review. RESULTS:Sixty-one studies form the evidence base. RECOMMENDATIONS:Patients with suspected stage III-IV EOC should be evaluated by a gynecologic oncologist, with cancer antigen 125, computed tomography of the abdomen and pelvis, and chest imaging included. All patients with EOC should be offered germline genetic and somatic testing at diagnosis. For patients with newly diagnosed advanced EOC who are fit for surgery and have a high likelihood of achieving complete cytoreduction, PCS is recommended. For patients fit for PCS but deemed unlikely to have complete cytoreduction, NACT is recommended. Patients with newly diagnosed advanced EOC and a high perioperative risk profile should receive NACT. Before NACT, patients should have histologic confirmation of invasive ovarian cancer. For NACT, a platinum-taxane doublet is recommended. Interval cytoreductive surgery (ICS) should be performed after ≤four cycles of NACT for patients with a response to chemotherapy or stable disease. For patients with stage III disease, good performance status, and adequate renal function treated with NACT, hyperthermic intraperitoneal chemotherapy may be offered during ICS. After ICS, chemotherapy should continue to complete a six-cycle treatment plan with the optional addition of bevacizumab. Patients with EOC should be offered US Food and Drug Administration-approved maintenance treatments. Patients with progressive disease on NACT should have diagnosis reconfirmed via tissue biopsy. Patients without previous comprehensive genetic or molecular profiling should be offered testing. Treatment options include alternative chemotherapy regimens, clinical trials, and/or initiation of end-of-life care.Additional information is available at www.asco.org/gynecologic-cancer-guidelines.This guideline has been endorsed by the Society of Gynecologic Oncology.

PURPOSE:Low-grade serous carcinoma (LGSOC) of the ovary, fallopian tube, or peritoneum is a hormonally driven, relatively chemoresistant malignancy with limited treatment options in the recurrent setting. Given frequent estrogen receptor (ER) expression and dysregulation of the cyclin-dependent kinases 4 and 6 (CDK4/6)-p16-Rb pathway, features shared with hormone receptor-positive breast cancer, dual endocrine, and CDK4/6 inhibition is a biologically rational strategy. This phase II trial evaluated ribociclib plus letrozole in recurrent LGSOC. METHODS:This open-label, single-arm, multicenter phase II study enrolled women with measurable, recurrent LGSOC. Patients received ribociclib (600 mg orally, once daily, days 1-21 of a 28-day cycle) and letrozole (2.5 mg orally, once daily). The primary end point was investigator-assessed objective response rate (ORR) per RECIST 1.1. Secondary end points included clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS:Of 74 patients screened, 51 were enrolled and 49 treated. The confirmed ORR was 30.6% (90% CI, 19.9 to 43.2), including one complete and 14 partial responses. Among responders, the median duration of response was 21.2 months. The CBR was 84% (90% CI, 72.5 to 91.6). The median PFS was 14.5 months (90% CI, 10.1 to 28.8), and the median OS was 44.5 months (90% CI, 31.8 to not reached). The most common grade ≥3 adverse event (AE) was neutropenia (47%), managed with dose modifications. Three grade 5 events (6%) occurred but were unrelated to treatment. Treatment discontinuation because of AEs occurred in 4%. No dose-limiting toxicities were observed. CONCLUSION:Ribociclib plus letrozole met the primary end point, achieving meaningful response rates and durable disease control in recurrent LGSOC. The safety profile was consistent with prior CDK4/6 inhibitor studies. This combination represents a therapeutic option in this rare and genomically distinct subtype.

5600 Background: In Part 1 of the phase 3 RUBY trial (NCT03981796) in pts with pA/rEC, dostarlimab + carboplatin-paclitaxel (DOST+CP) significantly improved progression-free survival and overall survival vs placebo (PBO)+CP. Patient-reported outcomes were a secondary endpoint. Here we present a post hoc analysis comparing timing of QoL improvement or deterioration by treatment. Methods: Pts were randomized 1:1 to receive DOST+CP or PBO+CP Q3W (6 cycles) followed by DOST or PBO monotherapy Q6W for ≤3 y. QoL was collected at each visit. Using data from the Sept 22, 2023 data cut (median follow-up 37.2 mo), analyses on time to first QoL improvement (TTI1) or deterioration (TTD1) were conducted for the EORTC QoL Questionnaire Core 30 (QLQ-C30) and Endometrial Cancer 24 (EN24) assessments using Cox regressions. Improvement or deterioration was classified ≥10-point change in the appropriate direction, per domain, from baseline. Results are reported for the primary study populations (overall and mismatch repair deficient/microsatellite instability-high [dMMR/MSI-H]). Results: A total of 494 pts were randomized, of which 118 were dMMR/MSI-H. For all QLQ-C30 and EN24 domains, TTI1 was similar between arms except pain in the overall population and role function in the dMMR/MSI-H population which reached nominal significance for earlier improvement in the DOST+CP arm (Table). The overall population had similar TTD1 in both arms, while time to deterioration was delayed in the DOST+CP arm for several domains (eg, global QoL, pain) in the dMMR/MSI-H population. Conclusions: With over 3 years of follow-up, DOST+CP was comparable to PBO+CP for TTI1 and TTD1 in the overall population of the RUBY trial and TTD1 was delayed in several QoL domains in the dMMR/MSI-H population. These results on patient experience of treatment further support the efficacy and safety data of dostarlimab for use in patients with pA/rEC. Clinical trial information: NCT03981796 . Overall population dMMR/MSI-H population DOST+CP (N=245)n PBO+CP(N=249)n HR, P value DOST+CP(N=53)n PBO+CP(N=65)n HR, P value Time to first improvementPainRole function 154111 13197 1.37, P =0.0081.28, P =0.076 3232 3726 1.20, P =0.4421.67, P =0.048 Time to first deteriorationGlobal QoLRole functionSocial functionPainSexual interestSexual activitySexual enjoymentUrological symptoms 194203200202126114105173 222219219218157143140201 0.85, P =0.1090.97, P =0.7960.97, P =0.7630.86, P =0.1190.82, P =0.1040.81, P =0.1020.77, P =0.0440.83, P =0.073 3336333719151330 5757575540343152 0.61, P =0.0270.58, P =0.0150.60, P =0.0200.63, P =0.0310.38, P =0.0010.42, P =0.0050.56, P =0.0920.50, P =0.003 n=number of patients with events. CP, carboplatin-paclitaxel; dMMR, mismatch repair deficient; DOST, dostarlimab; MSI-H, microsatellite instability-high; PBO, placebo.

ObjectiveDue to limited data on homologous recombination deficiency (HRD) in older patients (≥ 70 years) with advanced stage high grade serous ovarian cancer (HGSC), we aimed to determine the rates of HRD at diagnosis in this age group.MethodsFrom the Phase 3 trial VELIA the frequency of HRD and BRCA1/2 pathogenic variants (PVs) was compared between younger (< 70 years) and older participants. HRD and somatic(s) BRCA1/2 pathogenic variants (PVs) were determined at diagnosis using Myriad myChoice® CDx and germline(g) BRCA1/2 PVs using Myriad BRACAnalysis CDx®. HRD was defined if a BRCA PV was present, or the genomic instability score (GIS) met threshold (GIS ≥ 33 & ≥ 42 analyzed).ResultsOf 1140 participants, 21% were ≥ 70 years. In total, 26% (n = 298) had a BRCA1/2 PV and HRD, 29% (n = 329) were HRD/BRCA wild-type, 33% (n = 372) non-HRD, and 12% HR-status unknown (n = 141). HRD rates were higher in younger participants, 59% (n = 476/802), compared to 40% (n = 78/197) of older participants (GIS ≥ 42) [p < 0.001]; similar rates demonstrated with GIS ≥ 33, 66% vs 48% [p < 0.001]. gBRCA PVs observed in 24% younger vs 8% of older participants (p < 0.001); sBRCA in 8% vs 10% (p = 0.2559), and HRD (GIS ≥ 42) not due to gBRCA was 35% vs 31% (p = 0.36).ConclusionsHRD frequency was similar in participants aged < 70 and ≥ 70 years (35% vs 31%) when the contribution of gBRCA was excluded; rates of sBRCA PVs were also similar (8% v 10%), thus underscoring the importance of HRD and BRCA testing at diagnosis in older patients with advanced HGSC given the therapeutic implications.

5606 Background: MMR deficiency (dMMR) is caused by aberrant expression of MMR proteins that mediate DNA repair. The loss can be explained by epigenetic regulation (epi-dMMR; MLH1 promoter hypermethylation preventing MLH-1 expression) or mutation (mut-dMMR; MMR proteins lost through deleterious mutations) accounting for 70%–75% and 25%–30% of dMMR/microsatellite instability–high (MSI-H) EC, respectively. The GARNET trial showed that mechanism of MMR loss did not influence response of EC to monotherapy with dostarlimab (DOST), an anti-PD-1. No data exist examining OS by mechanism of MMR loss in patients (pts) with EC receiving immunotherapy. Here, we report analyses of PFS and OS in pts with primary advanced or recurrent EC (pA/rEC) in Part 1 of the RUBY trial (NCT03981796) by mechanism of MMR protein loss. Methods: Pts with pA/rEC were randomized 1:1 to receive DOST or placebo (PBO), plus carboplatin-paclitaxel (CP), followed by DOST or PBO monotherapy for up to 3 years. MMR protein status was assessed by immunohistochemistry. MMR loss of function gene mutations were determined by Personalis ImmunoID NeXT whole-exome sequencing assay. MMR protein loss without mutations in MMR genes was a surrogate indicator for epi-dMMR. Post hoc PFS and OS analyses utilized data from the data cut at which each endpoint was met (PFS at Sep 28, 2022; OS at Sep 22, 2023). Results: Part 1 of the RUBY trial included 118 pts with dMMR/MSI-H pA/rEC (DOST+CP = 53; PBO+CP = 65); 39 pts (73.6%) in the DOST+CP arm and 52 pts (80.0%) in the PBO+CP arm had MMR gene mutation data available. Substantial PFS and OS benefits were observed with DOST+CP vs PBO+CP in pts with mut-dMMR or epi-dMMR (Table). No significant differences were seen in PFS or OS in pts with mut-dMMR vs pts with epi-dMMR. Conclusions: DOST+CP led to substantial PFS and OS benefits compared with PBO+CP indMMR/MSI-H pA/rEC, regardless of mechanism of MMR protein loss. A limited number of pts with mut-dMMR treated with DOST+CP were available for analysis; however, the results support that mechanism of MMR loss does not appear to be a significant predictor of clinical benefit for dostarlimab treatment in pts with dMMR pA/rEC in Part 1 of the RUBY trial. Clinical trial information: NCT03981796 . [Table: see text]

5603 Background: The current treatment recommendation for advanced endometrial cancer is primary cytoreductive surgery, if feasible, or neoadjuvant chemotherapy (NACT) followed by surgery. To date, no randomized trials have compared these approaches in patients with stage III/IV endometrial cancer, and there is limited evidence or guidance for using NACT. The objectives of this study were to assess the national trend over time in the rates of primary surgery versus NACT in advanced endometrial cancer and to compare patient characteristics, outcomes, and complications between cohorts to provide insight into patient selection for either treatment paradigm. Methods: The National Cancer Database (NCDB) was queried for patients diagnosed with stage III/IV endometrial cancer between 2004 to 2019. Cohorts included primary surgery followed by chemotherapy, NACT followed by surgery, and chemotherapy alone. The primary outcome was the annual rate of primary surgery versus NACT followed by surgery over the study duration. Secondary outcomes were length of stay, 30-day readmission rate, and 30- and 90-day mortality following surgery. Patient characteristics, readmission rates, and mortality were compared using Chi-squared tests. A Wilcoxon Rank Test was used to assess the length of stay. Results: 23,155 patients met inclusion criteria. 3,268 received NACT followed by surgery, 13,161 received primary surgery, and 6,726 received chemotherapy alone. Age, race, ethnicity, median income, distance to a hospital, and comorbidities were similar between cohorts. The proportion of patients receiving NACT followed by surgery increased from 10.4% to 22.8%. Those undergoing primary surgery decreased from 51.7% to 40.6%. Patients receiving NACT were more likely to be stage IVB (61.0% vs. 32.70%), have serous histology (32.2% vs. 20.2%) and have public insurance (51.3% vs. 46.9%). Patients receiving NACT were less likely to be stage III (33.2% vs. 63.6%), and have endometrioid histology (37.3% vs. 47.6%). The length of stay following surgery was not significantly different between cohorts. Unplanned 30-day readmissions were higher in the primary surgery cohort (4.4% vs. 3.0%, p<0.001). 30-day mortality (0.9% vs. 0.2%, p<0.001) and 90-day mortality (5.5% vs. 2.2%, p<0.001) were higher in the NACT cohort. Conclusions: In advanced endometrial cancer, the utilization of NACT has increased nationally over the last two decades, while primary surgery has declined. Unplanned admissions were higher in the primary surgery group, but unexpectedly 30- and 90-day postoperative mortality were higher in the NACT group. Formal phase III trials to assess NACT vs surgery should be planned in patients with advanced endometrial cancer. Further research is necessary to determine baseline differences between cohorts in order to identify which patients would benefit from a neoadjuvant chemotherapy strategy.

e17596 Background: Laparoscopic surgery offers equivalent oncologic outcomes as compared to open surgery, while causing lesser morbidity and resulting in a faster recovery. However, vaginal extraction of specimens may cause vaginal or perineal lacerations (VL). To date, no studies have specifically reported the impact of vaginal laceration on local recurrence after surgical treatment for endometrial cancer. The objective of this study is to assess local recurrence rates compared between cases with or without vaginal lacerations (NL). Methods: We identified all patients with endometrial cancer who underwent laparoscopic surgical management between 2014 and 2018. We assessed the rate of local recurrence between patients in VL and NL cohorts. The study included all histologic subtypes and stages. Patients with benign final pathology, cases of synchronous primaries or cases that required laparotomy for extraction were excluded. Results: Among the 540 endometrial cancer MIS cases, 338 were evaluable. There were 40 cases of vaginal laceration during specimen extraction. There was no significant difference in age, race, presence of LVSI, stage, grade, histology or use of vaginal brachytherapy between cohorts. Cases with vaginal lacerations were significantly associated with a higher median BMI of 33.6kg/m2 (range 18.9-66) in the VL group as compared to 32.3kg/m2 (range 19.1-66) in the NL group (p=0.03). Uterine size was greater in the laceration group (VL) with a median of 150.5 g (49 - 462g) versus 110g (33 – 573g) in the NL cohort (p <0.01). The VL cohort was more likely to have received adjuvant treatment. Specifically external beam radiation therapy (EBRT) was administered 20% in the VL group versus 8.4% in the NL group (p = 0.02) and chemotherapy was used in 27.5% of the VL group versus 9.7% in the NL group (p < 0.01). In early stage disease, more cases had non-endometrioid histology in the VL group (23% versus 11.5%, p=0.043) and had increased incidence of chemotherapy and radiation use as well (EBRT 5.6% vs 23% and chemotherapy 6.7% versus 23%, both with p= <0.01). There were no cases of isolated vaginal recurrence (0/40) in the VL group as compared to an incidence of 2% (7/298) in the NL group with a relative risk of 0.48 (CI: 0.03-8.36, p=0.62). There were 4 cases of pelvic recurrence (4/40) in the VL group and 2 cases in the NL group (2/298) with a relative risk of 2.13 (CI: 0.46-9.89, p=0.34). Conclusions: In endometrial cancer cases, we did not observe a significantly increased risk of vaginal or pelvic recurrence after a vaginal laceration at the time of specimen removal. This could be attributed to the higher rate of non-endometrioid histology in early stage disease, which resulted in higher rates of adjuvant chemotherapy or radiation treatment.