Supplemental Table 2 shows the weighted prevalence of LNG-IUS use by different sociodemographic characteristics as stratified by race/ethnic groups.

Supplemental Table 1 shows the sociodemographic and medical history characteristics of the NSFG sample as stratified by race/ethnic groups.

BACKGROUND:This is the third updated enhanced recovery after surgery (ERAS®) society guideline presenting a consensus for optimal perioperative care in gynecologic oncology surgery. METHODS:A database search of publications using Embase and PubMed was performed (2018-2025). Studies for key elements within the ERAS gynecologic oncology protocol were selected with emphasis on meta-analyses, randomized controlled trials, and large prospective cohort studies. These studies were then reviewed and graded according to the grading of recommendations, assessment, development and evaluation (GRADE) system. RESULTS:All recommendations on ERAS protocol items are based on best available evidence. The level of evidence for each item is presented accordingly. CONCLUSIONS:The updated evidence base and recommendation for items within the ERAS gynecologic oncology perioperative care pathway are presented by the ERAS® society in this consensus review. Gynecologic surgeons may consider incorporating these recommendations into perioperative pathway design, with efforts to achieve consensus within their practice where feasible.

Objective Same-day discharge after minimally invasive hysterectomy has become increasingly feasible with the implementation of enhanced recovery after surgery (ERAS) pathways. However, predictors of same-day discharge within standardized ERAS programs remain incompletely defined. We aimed to identify patient, surgical, and perioperative factors associated with same-day discharge following minimally invasive hysterectomy for uterine cancer at a tertiary cancer center. Methods We conducted a retrospective cohort study of women undergoing minimally invasive hysterectomy for uterine cancer within a standardized ERAS pathway between January 2020 and December 2024. Demographic, clinical, operative, and ERAS compliance data were extracted from electronic medical records. Patients were categorized by discharge status (same-day discharge vs non-same-day discharge). Univariable and multivariable logistic regression analyses were performed to identify predictors of same-day discharge, reporting odds ratios (OR) with 95% confidence intervals (CI). Results Among 972 patients, 633 (65%) achieved same-day discharge. In univariable analysis, later surgery start time, older age, higher body mass index, non-Hispanic ethnicity, higher Charlson Comorbidity Index, longer operative time, greater estimated blood loss, and postoperative nausea and vomiting were associated with reduced odds of same-day discharge, while ERAS compliance was not. In multivariable analysis, later surgery start time (10:00 AM–1:59 PM: OR 0.68, 95% CI 0.49–0.95; p=0.001; 2:00 PM–midnight: OR 0.16, 95% CI 0.11–0.24; p<0.001), non-Hispanic ethnicity (OR 0.67, 95% CI 0.46–0.99; p=0.024), higher Charlson Comorbidity Index (OR 0.84, 95% CI 0.77–0.92; p<0.001), and PONV (OR 0.67, 95% CI 0.49–0.90; p=0.009) remained independently associated with lower likelihood of same-day discharge. Conclusion Approximately two-thirds of patients achieved same-day discharge following minimally invasive hysterectomy for uterine cancer within an ERAS pathway. Higher comorbidity burden, postoperative nausea and vomiting, and later surgery start time were key barriers to same-day discharge, highlighting opportunities for improved risk stratification, perioperative symptom management, and surgical scheduling.

Leiomyosarcoma is a smooth muscle-derived malignancy marked by significant clinical heterogeneity. The extent and nature of cellular heterogeneity and molecular underpinnings remain poorly understood. To address this at transcriptomic and epigenomic levels, we performed single-nucleus multiome sequencing on untreated primary leiomyosarcoma tissues. Malignant cells segregated almost exclusively into two previously unrecognized and epigenetically distinct states: a dedifferentiated, mesenchymal-like subtype (MES) and a differentiated smooth muscle-enriched subtype (SMC). Chromatin accessibility profiling revealed strong enrichment of nuclear factor I (NFI) transcription factor motifs in MES cells, whereas AP-1 family motifs-most prominently FOSL2-were selectively accessible in SMC cells. Established leiomyosarcoma cell lines faithfully recapitulated these subtypes, and targeted depletion of NFI or AP-1 factors suppressed proliferation, invasion, and in vivo tumor growth, demonstrating functional dependency on these transcriptional programs. Spatial transcriptomics across 328 tissue cores from 128 leiomyosarcomas showed that immunosuppressive macrophages preferentially cluster around MES regions, revealing a subtype-specific tumor-immune niche. Clinically, MES-dominant tumors were associated with significantly worse patient outcomes. Through an epigenetic inhibitor screen, we identify and validate SMARCA4/2 inhibition as a promising therapeutic vulnerability for MES leiomyosarcomas. Together, this work defines two epigenetically driven, transcription factor-regulated, and clinically relevant states of leiomyosarcoma, revealing mechanistic underpinnings of tumor heterogeneity and uncovering actionable therapeutic strategies.

Supplemental Table 3 shows the association of demographic and health predictors on current LNG-IUS use as stratified by race/ethnic groups.

OBJECTIVE:Small cell neuroendocrine carcinoma is a rare, aggressive histologic sub-type of cervical cancer. Although a standard frontline regimen exists, no standard highly active agent is available for recurrent disease. Single-agent anti-programmed cell death 1 therapy has also failed to demonstrate efficacy in this population; however, dual immune checkpoint blockade of programmed cell death 1 and cytotoxic T-lymphocyte-associated protein 4 has shown promising activity in high-grade neuroendocrine neoplasms. Data specific to recurrent small cell neuroendocrine cervical cancer remain sparse. We examined the safety and efficacy of cadonilimab, a bispecific antibody targeting programmed cell death 1 and cytotoxic T-lymphocyte-associated protein 4, in recurrent or metastatic small cell neuroendocrine cervical cancer. METHODS:This was a phase 2, open-label, single-arm study of cadonilimab monotherapy in patients with recurrent or metastatic high-grade small cell neuroendocrine cervical cancer. Eligible patients received 6 mg/kg of cadonilimab on days 1 and 15 of each 28-day treatment cycle for up to 24 months. The primary objective was to estimate the 6-month progression-free survival probability using Kaplan-Meier analysis. Progression-free survival was defined as the time from treatment initiation to disease progression or death from any cause. RESULTS:Among 9 patients who initiated treatment, 8 were evaluable for efficacy. One patient remained progression-free at 6 months (probability 0.125, 95% confidence interval 0.02 to 0.78). The median progression-free survival for the efficacy cohort was 2.19 months (95% confidence interval 1.84 to not available). The objective response rate was 0% (95% confidence interval 0% to 37%). Two patients experienced stable disease lasting 9.4 and 16.2 weeks, resulting in a disease control rate of 25% (2/8; 95% confidence interval 3% to 65%). One patient (1/9, 11%) experienced grade 3 fatigue. No grade 4 or 5 adverse events occurred. CONCLUSIONS:Cadonilimab monotherapy for recurrent or metastatic small cell neuroendocrine cervical cancer was safe; however, no objective responses were observed.

Objective To analyze molecular, clinicopathologic, and survival characteristics of patients with endometrial neuroendocrine tumors (ENETs) and evaluate outcomes by stage and treatment modality. Methods This retrospective cohort study included 97 individuals with histologically confirmed ENETs who received treatment at MD Anderson Cancer Center between January 1994 and October 2023. Clinicopathologic, molecular, treatment and outcome data were abstracted. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier curves, and associations with stage and treatment were evaluated using Cox proportional hazards models. Results 64% (62/97) of patients had FIGO stage III/IV disease. Large cell (31%), small cell (14%), and neuroendocrine carcinoma not otherwise specified (56%) were among histologic subtypes. 34% (33/97) received surgery followed by chemotherapy, 22% (22/97) were treated with surgery alone, and 23% (22/97) underwent surgery followed by both chemotherapy and radiation. 37 patients (38.1%) experienced disease progression on primary therapy, and 22 patients (22.6%) had recurrent disease. Advanced disease (Stages III and IV) was associated with shorter PFS (HR = 1.74, p = 0.0446). Adjuvant radiation, with or without chemotherapy, improved PFS (HR = 0.36, p = 0.003) and OS (HR = 0.43, p = 0.022). No significant differences were observed between carboplatin/paclitaxel and cisplatin/etoposide for PFS (p = 0.57) or OS (p = 0.77). Mutations in PTEN, ARID1A, and PIK3CA were most common. 53% of tumors were mismatch repair deficient, primarily MLH1/PMS2 loss. Conclusions ENETs are rare, aggressive tumors often diagnosed at an advanced stage. Combined adjuvant chemotherapy and radiotherapy were associated with improved outcomes. Molecular profiling may identify potential therapeutic targets.

BACKGROUND:Standardized prescribing models can reduce discharge opioid prescriptions and excess pill volumes, mitigating potential opioid dependence and diversion after abdominal operations. This study's objective was to determine which of 2 validated discharge prescribing models resulted in fewer opioids prescribed and consumed after major abdominal surgery. METHODS:This was a pragmatic single-center, phase II randomized clinical trial comparing 2 discharge opioid prescribing models: linear 5x-multiplier algorithm [last 24 h oral morphine equivalents (OME) times 5] versus capped 3-tier model (5/15/30 pills depending on 0/1-29/≥30 mg OME in last 24 h). Adults undergoing open abdominal cancer resections by 25 surgeons (5 specialties) were included. A nonopioid analgesic bundle was used perioperatively and at discharge. Coprimary endpoints were discharge opioid volume and 14-day post-discharge consumption. Secondary endpoints included patient satisfaction and symptom inventory. The power (80%) calculation was performed using the 2-sample t -test to detect a mean difference in OME with 0.05 significance (0.025 per co-primary outcomes). RESULTS:From April to December 2024, 150 patients (52% female; median age 63) were randomized: 73 to 5x-multiplier; 77 to 3-tier model. Operations included hepatectomy (32%), pancreatectomy (29%), nephrectomy (13%), thoracoabdominal sarcoma resection (15%), and ovarian cytoreduction (11%). Median discharge OME was 25 mg (5x-multiplier) versus 75 mg (3-tier, P <0.001), with 44% of 5x-multiplier patients discharged opioid-free (1% in 3-tier). Median post-discharge 14-day opioid consumption was 0 mg (5x-multiplier) versus 10 mg (3-tier, P =0.496). Refill rates were 24% (5x-multiplier) versus 18% (3-tier, P =0.426), consistent with historical rates, with no differences in satisfaction or symptom inventory scores. CONCLUSION:The 5x-multiplier algorithm resulted in fewer prescribed discharge opioids with similar 14-day consumption, refill rates, and satisfaction, compared with a 3-tier model after intra-abdominal cancer surgery.

BACKGROUND: Ovarian cancer is associated with delayed diagnosis and poor survival; thus, interest is high in identifying predictive and prognostic biomarkers and novel therapeutic agents. Although the costs of ovarian cancer care are likely to increase as newer, more effective, but more expensive treatment regimens become available, information on the current costs of care for ovarian cancer-across the care continuum from diagnosis to the end of life-are lacking. OBJECTIVE: This study aimed to estimate real-world mean and median costs of ovarian cancer care within the first 5 years after diagnosis by patients' phase of care, age, race/ethnicity, and geographic region. STUDY DESIGN: We performed a retrospective cohort study of ovarian cancer patients diagnosed between January 1, 2015 and December 31, 2020. We used claims data from Optum's deidentified Clinformatics Data Mart database, which includes inpatient, outpatient, and prescription claims for commercial insurance and Medicare beneficiaries nationwide. Cost of ovarian cancer care were calculated for the start of care (ie, the first 6 months), continuing care (ie, period between the initial and end-of-life care), and end-of-life care (ie, the last 6 months) phases and reported in 2021 U.S. dollar amounts. Ovarian cancer care costs were stratified by age, race/ethnicity, and geographic region. Due to the skewed nature of cost data, the mean cost data were log-transformed for modeling. Ordinary least-squares regression was conducted on the log costs, adjusting for patient categorical age, race/ ethnicity, and geographic region. RESULTS: A total of 7913 patients were included in the analysis. The mean cost per year for ovarian cancer care was >$200,000 during the start of care, between $26,000 and $88,000 during the continuing care phase, and >$129,000 during the end-of-life care phase. There were statistically significant associations between age and costs during each phase of care. Compared to younger patients, older patients incurred higher costs during the continuing care phase and lower costs during the end-of-life care phase. Geographic differences in the costs of ovarian cancer care were also noted regardless of the phase of care. There were no associations between cost and race/ethnicity in our cohort. CONCLUSION: Ovarian cancer care costs are substantial and vary by the phase of care, age category, and geographic region. As more effective but expensive treatment options for ovarian cancer become available with potential survival benefit, sustainable interventions to reduce the cost of care for ovarian cancer will be needed throughout the cancer care continuum.

Objectives: Current, real-world healthcare cost information is needed to project future expenditures and inform policy. We estimated the healthcare costs for adults in 2019 in the United States by age, sex, race/ethnicity, geographic region, and comorbidity. Methods: We aggregated and summarized the healthcare costs in 2021 US dollars using claims data derived from Optum's deidentified Clinformatics (R) Data Mart Database, which includes inpatient, outpatient, and prescription claims for commercial and Medicare Advantage beneficiaries nationwide. Results: A total of 9 227 901 adults were included in the analysis. The largest group represented was 71 to 75 years old (13%), female (53%), White (68%), received care in the South (41%), and had commercial health insurance (56%). There was a positive relationship between healthcare cost and age. Females had a 1.3-fold multiplicative increase in costs than males (95% CI 1.33-1.34). There were 92.5% of individuals who had health claims in the Northeast, 89.6% in the Midwest, 88.9% in the South, 77.1% in the West, and 12.7% with unknown geographic region. Patients with severe renal failure, heart failure, or metastatic cancer incurred the highest mean yearly costs ($139 844, $113 031, and $85 299, respectively). Metastatic cancer and severe renal failure were associated with a 5.3-fold multiplicative increase in costs than not having these conditions, after adjusting for potential confounders (95% CI 5.26-5.41 and 4.98-5.16, respectively). Conclusions: We identified patient characteristics and medical conditions that are associated with high healthcare cost burden and could benefit from tailored interventions. We provided detailed cost estimates to aid healthcare modeling, cost projection, and cost-minimizing interventions.

(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.

11508 Background: Leiomyosarcoma (LMS) is a smooth muscle-derived tumor with significant heterogeneity and limited treatment options for recurrent/metastatic disease. A lack of targetable driver mutations and prognostic and predictive biomarkers have hampered the care of patients with LMS. There is a great need to better understand the biology of LMS and develop novel therapeutics. Advances in single cell RNA sequencing (scRNA-seq) have allowed for better understanding of intratumoral heterogeneity in diverse cancer subtypes. However, tissue dissociation during this process leads to loss of spatial context. Spatial gene expression analysis builds upon scRNA-seq and has the potential to yield information about tissue organization, cell-cell interactions, niches, and cell states. To date there have been limited application of spatial transcriptomics to sarcoma. Methods: We performed single nucleus multiome (snRNA-seq and snATAC-seq) on a cohort of 16 primary, untreated LMS samples including 12 soft tissue (STLMS) and 4 uterine (ULMS) tumors. We then designed a custom 480-gene panel using the differentially expressed genes from clusters identified in snRNA-seq data to be able to identify spatial relationships between these clusters and to assess these clusters on a larger scale. We utilized the 10x Genomics Xenium platform. This was applied to LMS tissue microarrays (TMAs) comprising a total of 326 tissue cores from 127 unique patients. Matched primary and metastatic samples from the same patient were available for 33 patients. Results: Analysis of scRNAseq data identified 2 distinct subtypes: a dedifferentiated subtype with mesenchymal features (MES) and a differentiated subtype with enrichment of smooth muscle cell markers (SMC). Integration of chromatin accessibility data from snATACseq showed enrichment of nuclear factor I (NFI) transcription factor (TF) motifs in the MES and AP-1 motifs in the SMC group. Whole genome sequencing did not reveal an obvious genomic etiology for these subtypes. Spatial transcriptomics was able to identify these 2 subtypes in a larger cohort of tumors. Consistent with snRNAseq data, we find that most tumors had almost exclusively either MES or SMC cells. We assessed spatial relationships between these subtypes and infiltrating immune cells. This revealed an enrichment in immunosuppressive macrophages and exhausted T cells in MES tumors compared to SMC tumors. Analysis of matched primary and metastatic tumors demonstrated that the subtype (MES or SMC) generally remains consistent between different sites of disease. Conclusions: We identify 2 novel LMS subtypes (MES and SMC) driven by distinct TFs. Spatial transcriptomic analysis confirmed the presence of these 2 subtypes in a larger cohort and demonstrated that MES tumors are associated with a more immunosuppressive tumor microenvironment.

11564 Background: ULMS is an aggressive uterine smooth muscle cancer. Surgery is standard for localized/advanced ULMS, and the use of adjuvant chemotherapy is controversial. Treatment may involve combination cytotoxic chemotherapy, typically doxorubicin-based regimens (D) or gemcitabine plus docetaxel (GT), which have poor (20-30%) response rates and high toxicity. Given the lack of randomized trial data, this single-center retrospective study compared D vs GT in the adjuvant and metastatic settings of ULMS. Methods: We included patients with confirmed histologic diagnosis of uterine leiomyosarcoma between 2000 and 2024 treated at MD Anderson Cancer Center with either D or GT. Patients were stratified by localized disease and receipt of adjuvant chemotherapy or metastatic disease and receipt of palliative chemotherapy with D or GT in the first-line setting. The primary objective was to assess recurrence-free survival (RFS) in those with localized tumors and progression-free survival (PFS) in those with metastatic tumors treated with either D or GT. RFS and PFS were defined as the time interval from the start time of first line chemotherapy (D or GT) to the time of recurrence/progression or death, whichever occurred first. Kaplan Meier and log rank tests were used to assess survival outcomes. Cox proportional hazards (PH) modeling evaluated whether either regimen independently predicted survival with adjustment for age, primary tumor size, and mitotic index. Data collection is ongoing, and propensity score matching will be performed. Results: We included 76 patients, including 36 with primary localized ULMS and 40 with advanced ULMS. In patients with localized disease, there was no significant difference in RFS between those treated with D vs GT in univariate (p = 0.17) or multivariate (HR (95% CI) = 1.21 (0.35, 4.15), p = 0.76) analyses. In patients with metastatic disease, GT was associated with inferior PFS than those treated with D (HR (95% CI) = 4.45 (1.38, 14.29), p = 0.01) after adjusting for age and primary tumor size in the multivariate Cox PH model. Conclusions: Treatment with D was associated with improved PFS for metastatic ULMS compared to treatment with GT. No significant difference in RFS was observed between the two regimens for localized disease. However, the study may have limited power to detect differences due to small sample size. Updated data analyses with a larger cohort will be presented at the meeting. Localized ULMS (n = 36) Metastatic ULMS (n = 40) Age of diagnosis (median, years) 51.0 52.3 Primary tumor size (median, cm) 10.1 11.0 Mitotic Index (>10 per 10 HPF) 77.8% (n = 28) 82.5% (n = 33) D GT D GT 16.7% (n = 6) 83.3% (n = 30) 30% (n = 12) 70% (n = 28) RFS/PFS (median, months) 10.8 (7.8, 23.0) 7.2 (4.5, 9.2) HR (95% CI) 1.21 (0.35, 4.15) 4.45 (1.38, 14.29) p-value 0.7612 0.0122 Overall Survival (median, years) 6.6 (2.5, 10.3) 4.6 (3.7, 6.7)

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.