Objective:Cesarean hysterectomy for placenta accreta spectrum (PAS) is associated with significant morbidity. The role of adjunctive procedures, including tranexamic acid administration, ureteral stent placement, and endoarterial embolization or balloon placement, in mitigating surgical morbidity during cesarean hysterectomy for PAS is currently under active investigation. This study aimed to assess temporal trends, characteristics, and outcomes associated with adjunctive procedures during cesarean hysterectomy for PAS. Study Design:This retrospective study used the Premier Perspective database in the United States. The study population included pregnant patients who underwent cesarean hysterectomies for PAS between 2016 and 2023. Targeted adjunctive procedures included tranexamic acid administration, ureteral stent placement, and endoarterial embolization or balloon placement. A multivariate model was created to assess the association between adjunctive procedures and surgical morbidity. Results:Among 4,337 cesarean hysterectomies for PAS, 39.3%, 24.6%, and 16.1% received tranexamic acid, ureteral stent placement, and endoarterial embolization or balloon placement, respectively. During the 8-year study period, tranexamic acid administration increased 5.7-fold from 11.7% to 66.4%, and ureteral stent placement increased 1.6-fold from 19.2% to 30.3% (both p-trend <0.001). Nearly two-thirds of patients had postpartum hemorrhage (62.6%), and nearly one in five had urinary tract injury (18.7%). These three adjunctive procedures were not associated with decreased postpartum hemorrhage or urinary tract injury. Conclusion:These data suggest that the utilization of tranexamic acid and ureteral stent placement is increasing during cesarean hysterectomy for PAS in the United States. Reflecting the increases in real-world practice, whether these adjunctive procedures improve surgical morbidity of cesarean hysterectomy for PAS warrants further investigation with prospective studies. Key Points:· Tranexamic acid and ureteral stent use increased during PAS cesarean hysterectomy.. · Endoarterial procedures showed no significant temporal increase.. · Surgical morbidity remained substantial despite adjunctive procedure use..

Objective:Updated ACOG guidelines recommend a combined approach of transvaginal ultrasound (TVUS) and endometrial sampling for evaluation of most postmenopausal bleeding (PMB). Although prior studies investigating the reliability of TVUS suggest that non-endometrioid endometrial cancer subtypes present with thinner endometrium, some included cases with incomplete endometrial visualization. We therefore evaluated endometrial thickness (ET) by cancer subtype while controlling for incomplete endometrial visualization. Methods:We performed a retrospective cohort study of patients with PMB who underwent TVUS followed by tissue-confirmed endometrial cancer at three academic centers (2013-2022). Cancers were classified as endometrioid or non-endometrioid (serous, clear cell, carcinosarcoma, undifferentiated). Fibroid presence, endometrial visualization, and race/ethnicity were recorded. Patients with incomplete endometrial visualization were excluded from endometrial thickness analysis. Appropriate nonparametric statistical comparisons were performed. Results:Among 171 analysis-eligible patients (121 endometrioid, 50 non-endometrioid), non-endometrioid cancers were more common among non-Hispanic Black (53%) than non-Hispanic White (20%) or Hispanic patients (25%). Patients with non-endometrioid cancers were more likely to have incompletely visualized endometria (34% vs 9.1%, p < 0.01). Among patients with complete visualization, mean ET did not differ between endometrioid and non-endometrioid cancers (16.9 vs 19.5 mm) or by race/ethnicity. ET ≤4 mm occurred in 5.6% of cancers with fully visualized endometria, without differences between subtypes. Conclusion:When endometrium was fully visualized, non-endometrioid cancers did not present with thinner ET than endometrioid cancers, and a 4 mm cutoff may miss 5.6% of cancers. Incomplete visualization, more common in non-endometrioid disease, may lead to additional missed diagnoses, supporting universal endometrial sampling for PMB.

To evaluate the association between intrauterine manipulator use and survival outcomes in patients undergoing minimally invasive hysterectomy for endometrial cancer because the oncologic effects of intrauterine manipulator use remain controversial. A comprehensive systematic review of the literature published up to December 31, 2024, was conducted with the PubMed, Scopus, Web of Science, and Cochrane Library databases. Two independent investigators screened comparative studies, including prospective or retrospective studies and randomized controlled trials, examining oncologic outcomes in patients with endometrial cancer who underwent minimally invasive hysterectomy with or without an intrauterine manipulator. Studies with insufficient outcome data, including those involving patients who underwent open abdominal hysterectomy and those published in languages other than English, were excluded. Data extraction and synthesis were performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. Random-effects analysis was used for data pooling. The primary outcomes were disease-free survival and overall survival. Confounding factors affecting prognosis and risk of bias were also evaluated. Between 2013 and 2024, 12 eligible studies, including 10 retrospective studies and two randomized controlled trials, enrolled 6,029 patients who underwent minimally invasive hysterectomy with an intrauterine manipulator and 4,776 patients without one. In the unadjusted pooled analysis, disease-free survival was lower in patients who underwent surgery with an intrauterine manipulator than in those without (nine studies, hazard ratio 1.18, 95% CI, 1.01–1.38, P =.04). Albeit statistically nonsignificant, the hazard ratio for all-cause mortality comparing intrauterine manipulator use with nonuse was 1.27 (six studies, 95% CI, 0.99–1.62, P =.06). Only a limited number of studies (4 of 12 studies, 33.3%) examined survival outcomes after adjustment for factors such as adjuvant treatment and tumor histology. Most studies (7 of 12, 58.3%) had a moderate risk of bias, and five (41.6%) had a serious risk of bias. This meta-analysis suggests that intrauterine manipulator use during minimally invasive hysterectomy may be associated with decreased disease-free survival in patients with endometrial cancer; however, the association with overall survival is marginal and did not reach statistical significance. Considering that most studies included in this meta-analysis were retrospective, did not adjust for prognostic factors such as postoperative treatment, and were of low to moderate quality, the associations found in this study warrant further investigation in future prospective trials. PROSPERO, CRD42023428140.

OBJECTIVE:Malignant ovarian germ cell tumors (MOGCTs) are rare non-epithelial ovarian malignancies. Although comprehensive surgical staging, including lymphadenectomy, is recommended by current guidelines, the prognostic benefit in early-stage disease remains uncertain. We evaluated patterns of lymphadenectomy use and its association with survival in stage T1 MOGCTs. METHODS:Using the National Cancer Database, we identified women with stage T1 MOGCTs diagnosed between 2018 and 2022. Multivariable log-linear regression was used to identify factors associated with lymphadenectomy. Propensity score inverse probability of treatment weighting (IPTW) was applied to estimate the association between lymphadenectomy and survival using weighted Kaplan-Meier and Cox proportional-hazards models. RESULTS:Among 740 patients, 47.3% underwent lymphadenectomy, with use declining from 53.3% in 2018 to 36.2% in 2022 (P = 0.02). Dysgerminoma histology (aRR 1.78, 95% CI: 1.19-2.66), larger tumor size (>150 mm, aRR 1.44, 95% CI: 1.03-2.01), and performance of hysterectomy (aRR 1.40, 95% CI: 1.04-1.87) were associated with increased likelihood of undergoing lymphadenectomy. The median number of nodes examined was 9 (IQR 4-16), with nodal metastases identified in 6.6% of cases, most commonly among dysgerminomas. After PS IPTW, patients who underwent lymphadenectomy were more likely to receive adjuvant chemotherapy (52.8% vs. 44.7%; SMD = 0.16), and lymphadenectomy was not associated with improved survival (aHR 1.23, 95% CI: 0.38-4.06). CONCLUSIONS:In stage T1 MOGCTs, lymphadenectomy was not associated with improved survival but was associated with higher rates of adjuvant chemotherapy use. Given the low rate of nodal metastasis and excellent survival outcomes, a selective approach to lymphadenectomy may be appropriate.

OBJECTIVE:We sought to identify efficient tumor molecular profiling strategies for patients with newly diagnosed stage III-IVA endometrial cancer. METHODS:We constructed a decision tree model to compare molecular profiling strategies. We considered testing options of mismatch repair (MMR), p53, and HER2 immunohistochemistry (IHC), and next generation sequencing (NGS, assessing for MMR protein, TP53 and POLE mutations). Strategies included (1) MMR/p53: MMR/p53 IHC at diagnosis, with HER2 IHC if p53 abnormal and NGS reserved for first progression/recurrence; (2) Selective NGS: MMR/p53 IHC at diagnosis, with immediate NGS and HER2 IHC if p53 abnormal, otherwise NGS at recurrence; (3) Universal NGS: NGS and HER2 IHC at diagnosis for all. Molecular subtype prevalence and six-year recurrence-free survival by subtype were derived from the GOG-0258 randomized trial. Outcomes included costs (2024 US$), timely NGS results (results available at recurrence/progression), and unnecessary NGS (NGS performed in patients who remained recurrence-free). RESULTS:Universal NGS resulted in unnecessary NGS in 57% of patients who remained recurrence-free, compared with 7% under the Selective NGS strategy and 0% with MMR/p53. MMR/p53 was the least costly strategy (mean cost $3772), followed by Selective NGS ($4186) and Universal NGS ($6250). Compared with MMR/p53, Selective NGS cost $2571 per additional timely NGS result, while Universal NGS cost $7600 per additional timely NGS result compared with Selective NGS. CONCLUSIONS:Selective molecular profiling of newly diagnosed stage III-IVA endometrial cancers using MMR and p53 IHC with reflex to NGS for p53-abnormal tumors improves testing efficiency and reduces unnecessary NGS compared with universal upfront NGS testing.

In 2003, the U.S. Food and Drug Administration (FDA) issued a black box warning on menopausal hormone therapy (MHT) products based on putative harm of secondary outcomes and incompletely collected and adjudicated data from the Women's Health Initiative (WHI) oral conjugated equine estrogens and medroxyprogesterone acetate study. Despite the specific parameters and limitations of the WHI study, these warnings were inappropriately generalized across all doses, formulations, and routes of administration, including local vaginal therapies, under the mandate to prescribe the "lowest effective dose for the shortest duration." After 22 years of clinical controversy, the U.S. Department of Health and Human Services and the FDA announced removal of the boxed warning on November 10, 2025. This decision was based on the FDA's independent and comprehensive review of the scientific literature, deliberations from an expert panel on July 17, 2025, and a 60-day public comment period. The FDA's transition to product-specific labeling, the removal of the mandate for the lowest effective dose for the shortest duration, and the inclusion of guidance on the optimal timing of MHT initiation within 10 years of menopause or before age 60 years, represent critical steps toward evidence-based menopause management. By replacing misleading information with accurate data, this regulatory shift facilitates individualized benefit-risk assessments and empowers shared decision making. Ultimately, these updates ensure that MHT use is optimized for the specific needs of each patient, integrating modern risk assessment with the latest clinical evidence to improve long-term health outcomes.

OBJECTIVE:To examine real-world patterns of systemic hormone therapy (HT) initiation and continuation among women with a diagnosis of menopause. METHODS:Using the Merative™ MarketScan® Research Databases (2009-2022), we identified women aged 45-60 years with menopause-related claims and at least 12 months of continuous enrollment. Patients with bilateral oophorectomy, breast or gynecologic cancers, or HT contraindications were excluded. Multivariable regression analyzed factors associated with HT initiation, formulation, and duration. RESULTS:Of 318,621 eligible women, 21.7% initiated systemic HT within 1 year. Predictors of HT initiation included younger age (adjusted odds ratio [aOR] 2.17; 95% CI, 2.12-2.23), prior hysterectomy (aOR 1.98; 95% CI, 1.77-2.21), and local hormone use (aOR 3.25; 95% CI, 3.05-3.47). Initiation was significantly lower among women with obesity (aOR 0.78; 95% CI, 0.75-0.81), diabetes (aOR 0.69; 95% CI, 0.66-0.72), and Black racial identification (aOR 0.78; 95% CI, 0.68-0.89). Initial formulations were estrogen plus progestogen (52.5%), estrogen-alone (32.4%), and progestogen-alone (15.1%). The median first-episode duration was 6.6 months; 38.8% of patients continued at 12 months. Black racial (adjusted hazard ratio [aHR] 1.52; 95% CI, 1.34-1.73) and Hispanic ethnic (aHR 1.43; 95% CI, 1.14-1.80) identities predicted faster discontinuation. Conversely, prior hysterectomy (aHR 0.75; 95% CI, 0.68-0.83) and concurrent local hormone use (aHR 0.84; 95% CI, 0.80-0.89) reduced discontinuation risk. CONCLUSION:Although one-fifth of women initiated systemic HT shortly after their diagnosis, low persistence and racial disparities among those who initiated reveal critical gaps in long-term menopause management. Furthermore, true real-world utilization is likely even lower due to underdocumentation in clinical coding. These findings underscore an urgent need for targeted, equitable interventions to improve treatment adherence and ensure consistent, comprehensive care for menopausal women.

OBJECTIVE:To evaluate the association between intrauterine manipulator use and survival outcomes in patients undergoing minimally invasive hysterectomy for endometrial cancer because the oncologic effects of intrauterine manipulator use remain controversial. DATA SOURCES:A comprehensive systematic review of the literature published up to December 31, 2024, was conducted with the PubMed, Scopus, Web of Science, and Cochrane Library databases. METHODS OF STUDY SELECTION:Two independent investigators screened comparative studies, including prospective or retrospective studies and randomized controlled trials, examining oncologic outcomes in patients with endometrial cancer who underwent minimally invasive hysterectomy with or without an intrauterine manipulator. Studies with insufficient outcome data, including those involving patients who underwent open abdominal hysterectomy and those published in languages other than English, were excluded. TABULATION, INTEGRATION, AND RESULTS:Data extraction and synthesis were performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. Random-effects analysis was used for data pooling. The primary outcomes were disease-free survival and overall survival. Confounding factors affecting prognosis and risk of bias were also evaluated. Between 2013 and 2024, 12 eligible studies, including 10 retrospective studies and two randomized controlled trials, enrolled 6,029 patients who underwent minimally invasive hysterectomy with an intrauterine manipulator and 4,776 patients without one. In the unadjusted pooled analysis, disease-free survival was lower in patients who underwent surgery with an intrauterine manipulator than in those without (nine studies, hazard ratio 1.18, 95% CI, 1.01-1.38, P =.04). Albeit statistically nonsignificant, the hazard ratio for all-cause mortality comparing intrauterine manipulator use with nonuse was 1.27 (six studies, 95% CI, 0.99-1.62, P =.06). Only a limited number of studies (4 of 12 studies, 33.3%) examined survival outcomes after adjustment for factors such as adjuvant treatment and tumor histology. Most studies (7 of 12, 58.3%) had a moderate risk of bias, and five (41.6%) had a serious risk of bias. CONCLUSION:This meta-analysis suggests that intrauterine manipulator use during minimally invasive hysterectomy may be associated with decreased disease-free survival in patients with endometrial cancer; however, the association with overall survival is marginal and did not reach statistical significance. Considering that most studies included in this meta-analysis were retrospective, did not adjust for prognostic factors such as postoperative treatment, and were of low to moderate quality, the associations found in this study warrant further investigation in future prospective trials. SYSTEMATIC REVIEW REGISTRATION:PROSPERO, CRD42023428140.

The 2023 International Federation of Gynecology and Obstetrics revision introduced stage IA3 to recognize a biologically favorable subset of low-grade endometrioid endometrial cancers characterized by superficial myometrial invasion, absence of substantial lymphovascular space invasion, and unilateral, intra-capsular ovarian involvement. This reclassification reflects an evolving understanding, shaped by pathology, molecular profiling, and outcomes research that many uterus-ovary endometrioid pairs are clonally related yet clinically indolent, challenging historical assumptions that all adnexal involvement warrants intensified adjuvant treatment. Emerging molecular data suggest that this pattern of disease reflects a form of restricted metastatic spread limited to the endometrium-ovary interface, where a uniquely compatible microenvironment allows localized implantation without widespread peritoneal dissemination. In this narrative review, we synthesize the current literature and prevailing schools of thought regarding the prognostic meaning of adnexal involvement, the distinction between synchronous double primaries and limited metastatic spread, and the implications of molecular classification for risk assessment. We summarize evidence indicating favorable survival in rigorously defined IA3 cohorts, while underscoring persistent uncertainties arising from retrospective study designs, variable pathologic thresholds, and incomplete molecular annotation. Rather than prescribing definitive management, this review frames IA3 as a testing ground for risk-adapted care that integrates meticulous pathology with molecular context, acknowledges areas of controversy, and identifies priorities for future research. Collectively, these perspectives aim to support thoughtful, individualized decision-making as the field converges on when "less may be more" for appropriately selected IA3 patients. Given the limited and retrospective nature of available data, definitive treatment recommendations cannot yet be made, reinforcing the need for prospective, molecularly stratified studies to inform future practice.

Given the challenges in accurately predicting birth timing, we sought to quantify the proportion of individuals who receive late-preterm steroids in routine clinical practice who ultimately deliver at term. This retrospective cohort study of singleton gestations used data from January 2021 to December 2024 from the Premier Healthcare Database. We calculated the proportion of late-preterm steroid exposures in women who delivered at term and analyzed rates by hospital. The cohort included 519 hospitals and 97,322 singleton delivery hospitalizations of women with late-preterm betamethasone exposure. Of these, 28.8% (28,021) delivered at term, which equated to 1.0% (28,021 of 2,800,799) of all singleton term births being exposed to late-preterm steroids. Adjusted hospital-level proportions of singleton term births in individuals exposed to late-preterm steroids ranged from 0% to 63% with a median of 29%, reflecting substantial heterogeneity in late-preterm steroid use. This study highlights the need to develop accurate prediction methods for preterm birth timing and policies to inform optimal late-preterm steroid use.

OBJECTIVE:To estimate the real-world incidence of abnormal uterine bleeding after oral anticoagulant initiation with a large national claims database, stratified by agent and age group. METHODS:We conducted a nested matched case-control study using the MarketScan Research Databases (2008-2022). Women 18 years of age or older initiating oral anticoagulants (warfarin, apixaban, rivaroxaban, dabigatran, and edoxaban) for deep venous thrombosis, pulmonary embolism, or atrial fibrillation or flutter were matched 1:5 to anticoagulant nonusers. The primary outcome was abnormal uterine bleeding (AUB) within 1 year. Secondary outcomes included the risk of hospitalizations, emergency department visits, and outpatient encounters related to AUB. All estimates were derived from conditional logistic regression models adjusted for matching factors and baseline clinical covariates. RESULTS:Among 276,911 anticoagulant users and 1,384,555 matched controls, the incidence of AUB was significantly higher in anticoagulant users (6.1% vs 3.0%, adjusted odds ratio [AOR] 1.81, 95% CI, 1.69-1.93). Anticoagulant users had higher odds of AUB-related hospitalization (0.8% vs 0.01%, AOR 62.32, 95% CI, 30.94-125.53), emergency department visits (0.9% vs 0.2%, AOR 5.78, 95% CI, 4.02-8.31), and outpatient encounters (4.6% vs 2.8%, AOR 1.42, 95% CI, 1.32-1.52). Women younger than 50 years of age had a greater relative increase in AUB (19.7% vs 9.2%, AOR 1.96, 95% CI, 1.79-2.14) compared with women 50 years of age or older (3.8% vs 2.0%, AOR 1.63, 95% CI, 1.50-1.78). Among all agents, rivaroxaban was associated with the highest risk of AUB. CONCLUSION:Oral anticoagulant therapy is associated with significantly increased odds of AUB, particularly among younger women. Rivaroxaban conferred the highest AUB risk.

BACKGROUND:It is unknown to what extent the surgical management of endometriosis occurs in the outpatient settings and which factors are associated with ambulatory vs inpatient surgical care. OBJECTIVE:The objective of this study was to perform a nationwide analysis comparing trends, clinical factors, disease manifestations, surgical approaches, and hospital charges between ambulatory and inpatient surgical cases for endometriosis. STUDY DESIGN:This serial cross-sectional study analyzed inpatient and ambulatory surgeries from 2016 to 2022 with a primary diagnosis of endometriosis. Inpatient surgeries were analyzed using the National Inpatient Sample, a nationally representative inpatient database. Ambulatory surgeries were analyzed using the Nationwide Ambulatory Surgery Sample, a nationally representative ambulatory surgical database. Surgical trends were analyzed using joinpoint regression and presented as the average annual percent change. Demographic and clinical characteristics associated with inpatient vs ambulatory surgery were reported. Surgical procedures, endometriosis involvement sites, and surgical complications were also compared between inpatient and ambulatory surgeries. RESULTS:A nationwide total of 70,535 weighted inpatient and 561,894 weighted ambulatory surgical encounters for endometriosis were identified between 2016 and 2022. Over the study period, inpatient surgical volume decreased by 49% from 14,080 cases in 2016 to 7110 cases in 2022 (average annual percent change, -11.5% [95% confidence interval, -14.4% to -8.7%]), whereas outpatient surgical volume increased by 17% from 73,270 cases in 2016 to 85,896 cases in 2022 (average annual percent change, 2.8% [95% confidence interval, 0.2%-5.4%]). Inpatient surgical cases were more likely to occur among patients who were older (median age, 40 vs 37 years), who had a higher Elixhauser comorbidity index, who were more likely to be enrolled in Medicaid insurance (20% vs 16%), and who lived in the lowest median income ZIP code quartile (26% vs 21%). Ovarian involvement (37% vs 26%), bowel involvement (10% vs 3%), multiorgan involvement (40% vs 30%), concurrent pelvic infection (3.0% vs 1.4%), and intraoperative complications were all more common among patients undergoing inpatient compared with ambulatory surgery. Hysterectomy with salpingo-oophorectomy was most frequent in the inpatient setting but also accounted for a large proportion of ambulatory procedures (61% vs 47%), with a significant shift of this operation from inpatient to ambulatory care over the study period. CONCLUSION:An increasing proportion of surgeries for endometriosis, including hysterectomy, is now being performed in the outpatient setting. Inpatient surgical cases are more common among medically complex patients and those with distinct socioeconomic characteristics.

BACKGROUND:With evolving prescription policies, the clinical utility of patient-centered opioid prescribing remains unclear. We evaluated whether a patient-centered opioid prescribing approach improves outcomes compared to default strategies: "treat all" (emulating opioid over-prescribing practices in the late 1990s and 2000s) or "treat none" (reflecting prescribing restrictions in Centers for Disease Control and Prevention 2016 guideline). METHODS:We conducted a decision curve analysis using electronic medical data from 1136 adult patients undergoing laparoscopic cholecystectomy for benign indications (October 2015 - December 2018) at an urban tertiary care center. Perioperative opioid needs were categorized as "none/low" or "medium/high" based on pain scores and opioid prescriptions/administrations from 30 days pre-operative to two weeks postoperative. RESULTS:Of 803 patients in the training dataset, 63.9 % required medium/high opioid levels. Key predictors included sex, preoperative medication use (opioids, acetaminophen, other nonsteroidal anti-inflammatory drug, antidepressants), emergent surgery, anesthesia type, and surgical indications. The prediction model's c-statistic was 0.65 (95 %CI: 0.58-0.71) and Brier score was 0.20 (95 % CI: 0.009-0.71) in the testing dataset. At an optimal threshold probability of 0.60, the prediction model correctly identified 16 more true positive cases per 100 patients needing medium/high opioid prescriptions than the "treat all" strategy, accounting for false positives. Across a threshold range of 0.18-0.91, the model-based strategy constantly outperformed both default strategies. CONCLUSION:Prediction-based, patient-centered opioid prescribing provides greater clinical utility across most thresholds.

OBJECTIVE:To compare end-of-life (EOL) care quality indicators for patients with gynecologic malignancies whose primary oncologist spoke their preferred language (language-concordant care) versus those who did not (language-discordant care). METHODS:We conducted a retrospective chart review of patients with gynecologic malignancies who died between March 1, 2020, and May 30, 2024. The primary outcome was performance on National Quality Forum (NQF) quality indicators, a composite of six measures of aggressive EOL care. We used multivariable logistic regression to examine associations between language-discordant care and aggressive EOL care, adjusting for age, insurance status, and cancer stage at diagnosis. RESULTS:Briefly, 83 patients met inclusion criteria; 60 (72.3%) received care from a language-concordant oncologist and 23 (27.7%) from a language-discordant oncologist. Discordant patients were more likely to identify as Hispanic or Asian and to have Medicaid insurance. Aggressive EOL care, defined as an NQF score ≥1, occurred in 87.0% of discordant patients compared with 60.0% of concordant patients (p = 0.0174). After adjusting for age, insurance, and cancer stage, language-discordant care was associated with more than six-fold higher odds of aggressive EOL care (adjusted odds ratios: 6.05, 95% confidence intervals: 1.38-26.53). CONCLUSION:Language discordance between patients and oncologists was associated with greater likelihood of aggressive EOL care in gynecologic oncology. Addressing language barriers is essential to improving equity and aligning care with patients' goals at the end of life.

OBJECTIVE:We assessed the underlying etiology of MMR deficiency (dMMR), genetic (germline/somatic) versus epigenetic hMLH1, and associations between response rate, and survival outcomes in patients with advanced and recurrent dMMR endometrial adenocarcinoma treated with immune checkpoint inhibitors. METHODS:The Endometrial Cancer Molecularly Targeted Therapy Consortium (ECMT2) database was used to identify patients with mismatch repair deficient (dMMR) tumors treated with pembrolizumab or dostarlimab from 2016 to 2023. Cases were categorized into two groups- germline Lynch Syndrome mutation (gLS) and somatic Lynch Syndrome mutation (sLS), or MLH1 promoter hypermethylation (hMLH1). Clinical and pathologic data included patient demographics, tumor characteristics, recurrence date, survival, and treatment. RESULTS:A total of 133 patients were included: gLS/sLS (n = 34, 25.6%) or hMLH1 (n = 99, 74.4%). Demographic and tumor characteristics, including stage at diagnosis and histology were similar between groups. The response rate was 57.1% for the entire cohort [55.9% gLS/sLS, 57.6% hMLH1; (p = 0.90)]. The survival outcomes were not significantly different in the gLS/sLS and hMLH1 groups [2-year progression-free survival: 68.0% and 59.0% (p = 0.77); 2-year overall survival: 70.9% and 62.2% (p = 0.55)], respectively. CONCLUSION:Our findings suggest that response to immune checkpoint inhibitors and survival outcomes are not associated with different mechanisms of dMMR.

Recent evidence suggests that use of menopausal estrogen-only therapy in patients who have undergone hysterectomy reduces breast cancer risk among patients at population risk for breast cancer as well as in those with pathogenic high-risk BRCA variants. A meta-analysis of 10 randomized trials of estrogen therapy compared with placebo among 14,282 participants at population risk noted that 3.6% those randomized to estrogen alone were diagnosed with breast cancer, compared with 4.7% of those randomized to placebo (relative risk 0.77; 95% CI, 0.65-0.91, P=.002). A matched prospective cohort study of 676 patients with BRCA mutations and intact breasts who used menopausal hormone therapy (MHT) found that the estimated 15-year cumulative incidence of breast cancer with estrogen alone compared with no MHT was 24.3%, compared with 47.3% in the matched nonusers of MHT (P<.0001). This evidence underscores the need for more data that specifically assess the effect of estradiol therapy among patients who have undergone hysterectomy. Until such data are available, counseling patients at risk for breast cancer who have completed childbearing and are planning surgery for benign gynecologic conditions should involve shared decision-making that addresses the future risk of breast and endometrial cancers, cardiovascular disease, as well as the morbidity associated with hysterectomy. When appropriate, such counseling should also describe the availability of uterine-sparing alternatives.