Real-world use of immune checkpoint inhibitors in advanced or recurrent endometrial cancer.

OBJECTIVE: The aim of this study was to describe real-world use of immune checkpoint inhibitors for women with advanced or recurrent endometrial cancer. METHODS: Adult women with advanced or recurrent endometrial cancer who received at least one line of systemic treatment between January 1, 2014 and November 1, 2020, then followed to May 31, 2021 in a nationwide electronic health record-derived de-identified database. Chi-Squared test or Welch's 2-sample t-tests were used to compare patient and clinical factors associated with immune checkpoint inhibitor treatment. Time to next treatment analyses were performed based on the treatment line of the immune checkpoint inhibitor. Sankey plots depicted patient-level temporal systemic treatment. RESULTS: During our study period, 326 women received their first immune checkpoint inhibitor treatment, increasing from 12 patients in 2016 to 148 in 2020. Factors associated with ever receiving immune checkpoint inhibitors included disease stage (p=0.002), mismatch repair (MMR)/microsatellite instability (MSI) status (p<0.001), performance status (p=0.001), and prior radiation receipt (p<0.001) and modality (p=0.003). The most common immune checkpoint inhibitor regimen was pembrolizumab (47.9%) followed by pembrolizumab and lenvatinib (34.7%). Immune checkpoint inhibitors were given as first, second, and third or greater lines of therapy in 24.5%, 41.7%, and 46.1% of evaluable patients. The median time to next treatment was significantly longer if given as an earlier line of treatment (p=0.008). There were significant differences in treatment line of immune checkpoint inhibitor by region (p=0.004), stage (p<0.001), and prior radiation receipt (p=0.014) and modality (p=0.009). Among 326 patients who received immune checkpoint inhibitors, 114 (34.9%) received subsequent treatment including chemotherapy (43.9%), additional immune checkpoint inhibitors (29.8%), and other (26.3%) with no differences in demographic or clinical characteristics based on the type of post-immune checkpoint inhibitor treatment. CONCLUSION: In an observational retrospective real-world database study, immune checkpoint inhibitors were used in 14.7% of patients with advanced or recurrent endometrial cancer across multiple lines of treatment, including after initial immune checkpoint inhibitor treatment.

Fifth Edition of the World Health Classification of Tumors of the Hematopoietic and Lymphoid Tissues: Mature T-cell, NK-cell and Stroma-Derived Neoplasms of Lymphoid Tissues.

This review focuses on mature T-cell, NK cell, and stroma-derived neoplasms in the 5th edition of the World Health Organization (WHO) classification of hematolymphoid tumors (WHO-HEM5), including changes from the revised 4th edition (WHO-HEM4R). Overall, information has expanded, primarily due to advancements in genomic understanding. The updated classification adopts a hierarchical format. The updated classification relies on a multidisciplinary approach, incorporating insights from a diverse group of pathologists, clinicians, and geneticists. Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract, EBV-positive nodal T- and NK-cell lymphoma, and several stroma-derived neoplasms of lymphoid tissues have been newly introduced or included. The review also provides guidance on how the WHO-HEM5 can be applied in routine clinical practice.

Disease progression, survival, and molecular disparities in Black and White patients with endometrioid endometrial carcinoma in real-world registries and GOG/NRG oncology randomized phase III clinical trials.

OBJECTIVE: Investigate racial disparities in outcomes and molecular features in Black and White patients with endometrioid endometrial carcinoma (EEC). METHODS: Black and White patients diagnosed with EEC who underwent hysterectomy ± adjuvant treatment in SEER, National Cancer Database (NCDB), the Genomics Evidence Neoplasia Information Exchange (GENIE) project (v.13.0), and eight NCI-sponsored randomized phase III clinical trials (RCTs) were studied. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for cancer-related death (CRD), non-cancer death (NCD), and all-cause death. RESULTS: Black (n = 4397) vs. White (n = 47,959) patients in SEER had a HR (95% CI) of 2.04 (1.87-2.23) for CRD and 1.22 (1.09-1.36) for NCD. In NCDB, the HR (95% CI) for death in Black (n = 13,468) vs. White (n = 155,706) patients was 1.52 (1.46-1.58) dropping to 1.29 (1.23-1.36) after propensity-score matching for age, comorbidity, income, insurance, grade, stage, LVSI, and treatment. In GENIE, Black (n = 109) vs. White (n = 1780) patients had fewer PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K-pathway-related gene mutations. In contrast, TP53 and DNA-repair-related gene mutation frequency as well as tumor mutational burden-high status were similar in Black and White patients. In RCTs, Black (n = 187) vs. White (n = 2877) patients were more likely to have advanced or recurrent disease, higher grade, worse performance status and progressive disease. Risk of death in Black vs. White patients in RCTs was 2.19 (1.77-2.71) persisting to 1.32 (1.09-1.61) after matching for grade, stage, and treatment arm while balancing age and performance status. CONCLUSIONS: Differences exist in clinical presentation, outcomes, and molecular features in Black vs. White patients with EEC in real-world registries and RCTs. Targeted-drug development, strategies to modify social determinants, and diverse inclusion in RCTs are approaches to reduce disparities.

What is new in the 5th edition of the World Health Organization classification of mature B and T/NK cell tumors and stromal neoplasms?

The classification of tumors is essential in the diagnosis and clinical management of patients with malignant neoplasms. The World Health Organization (WHO) provides a globally applicable classification scheme of neoplasms and it was updated several times. In this review, we briefly outline the cornerstones of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours on lymphoid neoplasms. As is adopted throughout the 5th edition of the WHO classification of tumors of all organ systems, entities are listed by a hierarchical system. For the first time, tumor-like lesions have been included in the classification, and modifications of nomenclature for some entities, revisions of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities are presented along with mesenchymal lesions specific to the stroma of lymph nodes and the spleen. In addition to specific outlines on constitutional and somatic genetic changes associated with given entities, a separate chapter on germline predisposition syndromes related to hematologic neoplasms has been added.

Immuno-Molecular Targeted Therapy Use and Survival Benefit in Patients with Stage IVB Cervical Carcinoma in Commission on Cancer®-Accredited Facilities in the United States.

PURPOSE: To investigate IMT use and survival in real-world stage IVB cervical cancer patients outside randomized clinical trials. METHODS: Patients diagnosed with stage IVB cervical cancer during 2013-2019 in the National Cancer Database and treated with chemotherapy (CT) ± external beam radiation (EBRT) ± intracavitary brachytherapy (ICBT) ± IMT were studied. The adjusted hazard ratio (AHR) and 95% confidence interval (CI) for risk of death were estimated in patients treated with vs. without IMT after applying propensity score analysis to balance the clinical covariates. RESULTS: There were 3164 evaluable patients, including 969 (31%) who were treated with IMT. The use of IMT increased from 11% in 2013 to 46% in 2019. Age, insurance, facility type, sites of distant metastasis, and type of first-line treatment were independently associated with using IMT. In propensity-score-balanced patients, the median survival was 18.6 vs. 13.1 months for with vs. without IMT (p < 0.001). The AHR was 0.72 (95% CI = 0.64-0.80) for adding IMT overall, 0.72 for IMT + CT, 0.66 for IMT + CT + EBRT, and 0.69 for IMT + CT + EBRT + ICBT. IMT-associated survival improvements were suggested in all subgroups by age, race/ethnicity, comorbidity score, facility type, tumor grade, tumor size, and site of metastasis. CONCLUSIONS: IMT was associated with a consistent survival benefit in real-world patients with stage IVB cervical cancer.

Survival disparities in non-Hispanic Black and White cervical cancer patients vary by histology and are largely explained by modifiable factors.

PURPOSE: We investigated racial disparities in survival by histology in cervical cancer and examined the factors contributing to these disparities. METHODS: Non-Hispanic Black and non-Hispanic White (hereafter known as Black and White) patients with stage I-IV cervical carcinoma diagnosed between 2004 and 2017 in the National Cancer Database were studied. Survival differences were compared using Cox modeling to estimate hazard ratio (HR) or adjusted HR (AHR) and 95% confidence interval (CI). The contribution of demographic, socioeconomic and clinical factors to the Black vs White differences in survival was estimated after applying propensity score weighting in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC). RESULTS: This study included 10,111 Black and 43,252 White patients with cervical cancer. Black patients had worse survival than White cervical cancer patients (HR = 1.40, 95% CI = 1.35-1.45). Survival disparities between Black and White patients varied significantly by histology (HR = 1.20, 95% CI = 1.15-1.24 for SCC; HR = 2.32, 95% CI = 2.12-2.54 for AC, interaction p < 0.0001). After balancing the selected demographic, socioeconomic and clinical factors, survival in Black vs. White patients was no longer different in those with SCC (AHR = 1.01, 95% CI 0.97-1.06) or AC (AHR = 1.09, 95% CI = 0.96-1.24). In SCC, the largest contributors to survival disparities were neighborhood income and insurance. In AC, age was the most significant contributor followed by neighborhood income, insurance, and stage. Diagnosis of AC (but not SCC) at ≥65 years old was more common in Black vs. White patients (26% vs. 13%, respectively). CONCLUSIONS: Histology matters in survival disparities and diagnosis at ≥65 years old between Black and White cervical cancer patients. These disparities were largely explained by modifiable factors.

Uterine cancer among Asian Americans - Disparities & clinical characteristics.

OBJECTIVE: To evaluate the patterns and trends of uterine cancer among Asian subgroups living in the U.S. METHODS: Data were obtained from United States Cancer Statistics (2001-2017), National Cancer Database (2004-2015), and World Population Review (2023). SEER*Stat version 8.3.9.2, Joinpoint regression program 4.9.0.0, and SAS v 9.4 were employed for statistical analysis. RESULTS: Based on data from 778,891 women in the United States Cancer Statistics database, Asians had a 3.4-fold higher rate of incident uterine cancer compared to White populations (2.14% vs. 0.63%; p < 0.001). Using the National Cancer Database, 7,641 Asian women from six subgroups were analyzed: Filipino, Korean, Indian/Pakistani, Vietnamese, Chinese, and Japanese. Indian and Pakistani women had the greatest increase in the proportion of cancer diagnoses (5.0% to 14.4%; p = 0.0003). Additionally, Indian and Pakistani patients had higher comorbidity scores while Koreans had the lowest (22.7% vs. 10.7%, p < 0.0001). Regarding stage of disease, 25.3% of Filipinos presented with advanced stage disease compared to 19.2% of Indians and Pakistanis (p = 0.0001). Furthermore, Filipinos had the highest proportion of non-endometrioid cancers at 18.4% compared to other subgroups (p = 0.0003). Using the World Population Review, female obesity was highest in Pakistan (8.6%) and the Philippines (7.5%) and lowest in Vietnam (2.6%). CONCLUSION: Uterine cancer incidence increased at higher rates among Asians compared to White populations. Specifically, Indian and Pakistani uterine cancer patients were more likely to have higher comorbidity rates and Filipino patients had more advanced stage cancer with non-endometrioid histologies than other Asian subgroups. Further research is warranted to better understand these trends.

Racial, ethnic and country of origin disparities in aggressive endometrial cancer histologic subtypes.

OBJECTIVE: This study investigated the risk of an aggressive endometrial cancer (EC) diagnosis by race, ethnicity, and country of origin to further elucidate histologic disparities in non-Hispanic Black (NHB), Hispanic, Asian/Pacific Islander (API), American Indian/Alaskan Native (AIAN) vs. non-Hispanic White (NHW) patients, particularly in Hispanic or API subgroups. METHODS: Patient diagnosed between 2004 and 2020 with low grade (LG)-endometrioid endometrial cancer (ECC) or an aggressive EC including grade 3 EEC, serous carcinoma, clear cell carcinoma, mixed epithelial carcinoma, or carcinosarcoma in the National Cancer Database were studied. The odds ratio (OR) and 95% confidence interval (CI) for diagnosis of an aggressive EC histology was estimated using logistic modeling. RESULTS: There were 343,868 NHW, 48,897 NHB, 30,013 Hispanic, 15,015 API and 1646 AIAN patients. The OR (95% CI) for an aggressive EC diagnosis was 3.07 (3.01-3.13) for NHB, 1.08 (1.06-1.11) for Hispanic, 1.17 (1.13-1.21) for API and 1.07 (0.96-1.19) for AIAN, relative to NHW patients. Subset analyses by country of origin illustrated the diversity in the OR for an aggressive EC diagnosis among Hispanic (1.18 for Mexican to 1.87 for Dominican), Asian (1.14 Asian Indian-Pakistani to 1.48 Korean) and Pacific Islander (1.00 for Hawaiian to 1.33 for Samoan) descendants. Hispanic, API and AIAN patients were diagnosed 5-years younger that NHW patients, and the risk for an aggressive EC histology were all significantly higher than NHW patients after correcting for age. Insurance status was another independent risk factor for aggressive histology. CONCLUSIONS: Risk of an aggressive EC diagnosis varied by race, ethnicity, and country of origin. NHB patients had the highest risk, followed by Dominican, South/Central American, Cuban, Korean, Thai, Vietnamese, and Filipino descendants.

The 5th edition of the World Health Organization Classification of mature lymphoid and stromal tumors - an overview and update.

The purpose of this review is to give an overview on the conceptual framework and major developments of the upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid tumours (WHO-HAEM5) and to highlight the most significant changes made in WHO-HAEM5 compared with the revised 4th edition (WHO-HAEM4R) of lymphoid and stromal neoplasms. The changes from the revised 4th edition include the reorganization of entities by means of a hierarchical system that is realized throughout the 5th edition of the WHO classification of tumors of all organ systems, a modification of nomenclature for some entities, the refinement of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities. For the first time, tumor-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms are included in the classification.

Preoperative and pre-chemotherapy CA-125 levels in high-risk early-stage ovarian cancer - An NRG/GOG study.

OBJECTIVES: To determine clinical significance of preoperative and pre-chemotherapy CA-125 in high-risk early-stage epithelial ovarian cancer patients. METHODS: All patients with stage IA/IB and grade 3, stage IC, clear cell, or completed resected stage II cancer were enrolled in a phase III trial and treated with chemotherapy. Kaplan-Meier method and Cox proportional hazards model were used for statistical analyses. RESULTS: 427 patients with high-risk early-stage ovarian cancer were enrolled. Of 213 patients with preoperative CA-125 data, 79% had elevated CA-125. Median preoperative CA-125 level was 103 U/mL. Patients with ≤10, 11-15, and > 15 cm tumors had median preoperative CA-125 levels of 62, 131 and 158 U/mL, respectively (p = 0.002). For the 350 patients with data for pre-chemotherapy CA-125 level, 69% had elevated pre-chemotherapy CA-125 above 35 U/mL with median value of 65 U/mL. However, age, race, stage, cell type and grade of disease were not correlated with CA-125 levels before and after surgery. On multivariate analysis, elevated pre-chemotherapy CA-125 independently predicted worse recurrence-free survival (HR = 2.13, 95% CI: 1.23-3.69; p = 0.007) and overall survival (HR = 1.99, 95% CI: 1.10-3.59; p = 0.022) after adjusting for age, stage, cell type and grade of disease. Compared to those with normal CA-125, patients with elevated pre-chemotherapy CA-125 had lower recurrence-free survival (RFS, 87% vs. 75%; p = 0.007) and overall survival (OS, 88% vs. 82%; p = 0.02). However, preoperative CA-125 was not prognostic of RFS (p = 0.699) or OS (p = 0.701). CONCLUSIONS: Preoperative CA-125 was elevated in nearly 80% of high-risk early-stage ovarian cancer patients. Pre-chemotherapy CA-125 was associated with recurrence-free and overall survival; however, preoperative CA-125 was not prognostic.

Exploring U.S. Hispanic origin groups diagnosed with uterine cancer - Are there disparities?

OBJECTIVE: To evaluate patterns and trends of uterine cancer among Hispanic subgroups. METHODS: The United States Cancer Statistics (USCS), National Cancer Database (NCDB), and World Population Review were used to obtain data on incidence, demographic characteristics, and cancer histology. Joinpoint regression program was used for statistical analysis. RESULTS: Based on 2001-2017 USCS data, the overall incidence of uterine cancer was 27.46 vs. 23.29/100,000 in Hispanics vs. non-Hispanic Whites. There was an over 2-fold higher annual increase in the incidence in Hispanics (1.94%; p < 0.001) vs. Whites (0.85%; p < 0.001), particularly in local stage disease. There was an increase in grade 1 endometrioid carcinoma (1.48%; p < 0.001 vs. -0.52%; p = 0.1) and aggressive histologic subtypes (4.04% p = 0.000 vs. 2.53% p = 0.000) in Hispanics vs. Whites. Using the NCDB (2004-2015), we analyzed 17,351 Hispanics by subgroup (Mexican, South/Central American, Puerto Rican, Cuban, and Dominican). Over the 12 years, there was an increase in the proportion of uterine cancer diagnoses in all Hispanics (5.2% to 11.0%; p < 0.0001). Dominican patients experienced the largest increase in diagnosis (2.6% to 14.9%; p < 0.0001), the highest proportion of advanced disease at 28.0% (p < 0.0001), and the highest incidence of non-endometrioid histologies at 37.1% (p < 0.0001). World Population Review 2023 revealed the highest female obesity rates in Puerto Rico (51.4%), the Dominican Republic (34.1%), and Mexico (32.8%). CONCLUSION: Uterine cancer incidence is increased in Hispanics, with the largest increase in Dominican women with more advanced stages and high-risk histologic subtypes. The impact of obesity on cancer risk, especially in Puerto Ricans, Dominicans, and Mexicans, warrants further investigation.

Underrepresentation of racial and ethnic minority groups in gynecologic oncology: An analysis of over 250 trials.

OBJECTIVE: To describe the participation of racial and ethnic minority groups (REMGs) in gynecologic oncology trials. METHODS: Gynecologic oncology studies registered on ClinicalTrials.gov between 2007 and 2020 were identified. Trials with published results were analyzed based on reporting of race/ethnicity in relation to disease site and trial characteristics. Expected enrollment by race/ethnicity was calculated and compared to actual enrollment, adjusted for 2010 US Census population data. RESULTS: 2146 gynecologic oncology trials were identified. Of published trials (n = 252), 99 (39.3%) reported race/ethnicity data. Recent trials were more likely to report these data (36% from 2007 to 2009; 51% 2013-2015; and 53% from 2016 to 2018, p = 0.01). Of all trials, ovarian cancer trials were least likely to report race/ethnicity data (32.1% vs 39.3%, p = 0.011). Population-adjusted under-enrollment for Blacks was 7-fold in ovarian cancer, Latinx 10-fold for ovarian and 6-fold in uterine cancer trials, Asians 2.5-fold in uterine cancer trials, and American Indian and Alaska Native individuals 6-fold in ovarian trials. Trials for most disease sites have enrolled more REMGs in recent years - REMGs made up 19.6% of trial participants in 2007-2009 compared to 38.1% in 2016-2018 (p < 0.0001). CONCLUSION: Less than half of trials that published results reported race/ethnicity data. Available data reveals that enrollment of REMGs is significantly below expected rates based on national census data. These disparities persisted even after additionally adjusting for population size. Despite improvement in recent years, additional recruitment of REMGs is needed to achieve more representative and equitable participation in gynecologic cancer clinical trials.

Trends in Uterine Cancer Mortality in the United States: A 50-Year Population-Based Analysis.

OBJECTIVE: To analyze mortality trends in uterine cancer in the United States over 50 years with an emphasis on age and race and ethnicity. METHODS: Data on uterine cancer deaths from 1969 to 2018 were obtained from the National Center for Health Statistics. Trends were examined by age and race and ethnicity after adjustment for the hysterectomy rate and pregnancy. RESULTS: Uterine cancer mortality decreased between 1969 and 1997 (from 6.03 to 4.00/100,000) but increased between 1997 and 2018 (from 4.00 to 5.02/100,000). From 2001 to 2018, mortality rates increased by 1.25-fold across all age groups. In 2018, the mortality rate from uterine cancer for patients aged 70 years or older and 60-69 years was sixfold and threefold higher, respectively, than in younger patients (aged 50-59 years) (54.87/100,000 vs 27.80/100,000 vs 8.70/100,000). The mortality rate for non-Hispanic Black women was 2.2-fold higher than for non-Hispanic White, Hispanic, and non-Hispanic Asian or Pacific Islander women (17.6/100,000 vs 7.82/100,000, 6.54/100,000, and 4.24/100,000, respectively). On an intersection analysis of age and race, non-Hispanic Black women aged older than 60 years had a threefold higher mortality rate than non-Hispanic White women (72/100,000 vs 24/100,000). A notable finding was that young non-Hispanic Black and Hispanic women (30-39 years) had the highest annual increases in mortality at 3.3% and 3.8% per year compared with 2.2% in non-Hispanic White women. CONCLUSION: Since 2001, the uterine cancer mortality rate has increased across all four racial and ethnic groups examined, with the highest increase seen among non-Hispanic Black women. The largest increase in mortality was observed among younger non-Hispanic Black and Hispanic women.

Sequential Targeted Therapy for Advanced, Metastatic, and Recurrent Cervical Cancer: A Cost-Effectiveness Analysis of the Patient Journey.

OBJECTIVES: To evaluate outcomes and cost-effectiveness of targeted therapy sequencing for metastatic and recurrent cervical cancer. METHOD: Models were simulated based on phase II and III trials on bevacizumab (bev) from GOG-240, cemiplimab (cemi) from GOG 3016, pembrolizumab (pembro) from KEYNOTE-826, and tisotumab vedotin (tiso) from GOG 3023. Costs were based on IBM Micromedex RED BOOK™ and company listed costs. RESULTS: For [chemo + bev → chemo], total cost was $125,918.04, with median overall survival (mOS) of 21.8 months, and cost-effectiveness ratio (CER) of $119,835.79. For [chemo + bev → cemi], total cost was $187,562.99 with mOS of 28.5 months and CER of $162,039.16. For [chemo + bev + pembro → chemo], total cost was $319,963.78 with mOS 32.9 months and CER of $249,930.10. For [chemo + bev + pembro → tiso], total cost was $455,204.45, with mOS 36.5 months and CER of $320,072.99. CONCLUSION: The combination of immunotherapies and biologics have significantly increased overall survival, but with associated higher costs, primarily related to drug costs.

Real-world Outcomes Associated With Poly(ADP-ribose) Polymerase Inhibitor Monotherapy Maintenance in Patients With Primary Advanced Ovarian Cancer.

OBJECTIVE: This study used real-world population data to assess the trends of first-line (1L) poly(ADP-ribose) polymerase inhibitor (PARPi) maintenance treatment uptake and outcomes in patients with primary advanced ovarian cancer (AOC). METHODS: Patients diagnosed with AOC between January 1, 2017, and June 30, 2021, who completed 1L chemotherapy were selected from a real-world database. Descriptive analyses were performed to evaluate patient demographics, clinicopathological characteristics, and 1L treatment patterns. Time to next treatment or death was used as a proxy for real-world progression-free survival (rwPFS). Kaplan-Meier methods and Cox models were used for statistical analyses. RESULTS: Of 705 patients who completed 1L chemotherapy, 166 received PARPi monotherapy and 539 underwent active surveillance (AS). Median follow-up was 10.9 months for PARPi monotherapy and 20.6 months for AS. PARPi monotherapy use increased from 6% in 2017 to 53% in 2021. Overall, patients receiving PARPi monotherapy had longer rwPFS than those who underwent AS (not reached vs 9.53 mo) respectively. rwPFS was also longer in patients who received PARPi monotherapy compared with AS in patients with BRCA- mutated disease (not reached vs 11.4 mo), BRCA- wild-type disease (13.5 vs 9.1 mo), homologous recombination-deficient tumors (not reached vs 10.2 mo), and homologous recombination-proficient or unknown status tumors (13.5 vs 9.3 mo). CONCLUSIONS: Our real-world analysis suggested that 47% of patients with primary AOC did not receive PARPi maintenance in the year 2021. PARPi use was associated with significantly improved outcomes compared with AS.

Factors Associated With Survival Disparities Between Non-Hispanic Black and White Patients With Uterine Cancer.

Importance: Disparities in survival exist between non-Hispanic Black (hereafter, Black) and non-Hispanic White (hereafter, White) patients with uterine cancer. Objective: To investigate factors associated with racial disparities in survival between Black and White patients with uterine cancer. Design, Setting, and Patients: This cohort study used data from the National Cancer Database on 274 838 Black and White patients who received a diagnosis of uterine cancer from January 1, 2004, to December 31, 2017, with follow-up through December 2020. Statistical analysis was performed in July 2022. Main Outcomes and Measures: Overall survival by self-reported race and evaluation of explanatory study factors associated with hazard ratio (HR) reduction for Black vs White patients. A propensity scoring approach was applied sequentially to balance racial differences in demographic characteristics, comorbidity score, neighborhood income, insurance status, histologic subtype, disease stage, and treatment. Results: The study included 32 230 Black female patients (mean [SD] age at diagnosis, 63.8 [10.0] years) and 242 608 White female patients (mean [SD] age at diagnosis, 63.5 [10.5] years) and had a median follow-up of 74.0 months (range, 43.5-113.8 months). Black patients were more likely than White patients to have low income (44.1% vs 14.0%), be uninsured (5.7% vs 2.6%), present with nonendometrioid histologic characteristics (46.1% vs 21.6%), have an advanced disease stage (34.1% vs 19.8%), receive first-line chemotherapy (33.8% vs 18.2%), and have worse 5-year survival (58.6% vs 78.5%). Among patients who received a diagnosis at younger than 65 years of age, the HR for death for Black vs White patients was 2.43 (95% CI, 2.34-2.52) in a baseline demographic-adjusted model and 1.29 (95% CI, 1.23-1.35) after balancing other factors. Comorbidity score, neighborhood income, insurance status, histologic subtype, disease stage, treatment, and unexplained factors accounted for 0.8%, 7.2%, 11.5%, 53.1%, 5.8%, 1.2%, and 20.4%, respectively, of the excess relative risk (ERR) among the younger Black vs White patients. Among patients 65 years or older, the HR for death for Black vs White patients was 1.87 (95% CI, 1.81-1.93) in the baseline model and 1.14 (95% CI, 1.09-1.19) after balancing other factors. Comorbidity score, neighborhood income, insurance status, histologic subtype, disease stage, treatment, and unexplained factors accounted for 3.0%, 7.5%, 0.0%, 56.2%, 10.6%, 6.9%, and 15.8%, respectively, of the ERR among Black vs White patients aged 65 years or older. Conclusions and Relevance: This study suggests that histologic subtype was the dominant factor associated with racial survival disparity among patients with uterine cancer, while insurance status represented the main modifiable factor for women younger than 65 years. Additional studies of interactions between biology and social determinants of health are merited.