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Endometrial cancer stage is a strong prognostic factor; however, the current stage classification does not incorporate transtubal spread as determined by intraluminal tumor cells (ILTCs). We examined relationships between ILTCs and survival outcomes according to histological subtype and stage and examined whether identification of ILTCs improves prognostic accuracy of endometrial cancer staging. We conducted a retrospective cohort study of women diagnosed with endometrial cancer at five academic hospitals between 2007 and 2012. Pathologists determined ILTC presence (no vs. yes) and location (free in lumen vs. attached to epithelial surface) based on pathology review of hematoxylin and eosin-stained sections of fallopian tubes. Associations between ILTCs with time to recurrence (TTR) and overall survival (OS) were examined with Cox proportional hazards models adjusted for other prognostic factors. Model discrimination metrics were used to assess the addition of ILTCs to stage for prediction of 5-year TTR and OS. In the overall study population (N = 1303), ILTCs were not independently associated with TTR (HR = 0.95, 95% CI = 0.69–1.32) or OS (HR = 0.97, 95% CI = 0.72–1.31). Among 805 women with stage I disease, ILTCs were independently associated with worse TTR (HR = 2.31, 95% CI = 1.06–5.05) and OS (HR = 2.16, 95% CI = 1.14–4.11). Upstaging early-stage cases with ILTCs present did not increase model discrimination. While our data do not suggest that endometrial cancer staging guidelines should be revised to include ILTCs, associations between ILTCs and reduced survival observed among stage I cases suggest this tumor feature holds clinical relevance for subgroups of endometrial cancer patients. • In endometrial cancer, the role of transtubal spread as determined by intraluminal tumor cell presence is controversial. • Presence of intraluminal tumor cells was not related to recurrence or overall survival in the overall study population. • Among women with stage 1 disease, intraluminal tumor cells were related to worse recurrence and overall survival. • Upstaging women with early-stage endometrial cancer with intraluminal tumor cells did not affect model discrimination. [ABSTRACT FROM AUTHOR]

Background Although unopposed estrogen exposure is considered a major driver of endometrial carcinogenesis, chronic inflammation and insulin resistance and hyperinsulinemia are also major endometrial cancer risk factors. However, it is unclear whether diets with inflammatory or insulinemic potential are associated with risk of endometrial cancer. Methods We followed 48 330 women from the Nurses' Health Study (1984-2016) and 85 426 women from the Nurses' Health Study II (1989-2017). Using food frequency questionnaires, we calculated repeated measures of empirical dietary inflammatory pattern (EDIP) and empirical dietary index for hyperinsulinemia (EDIH) scores, which characterize the potential of the whole diet to modulate circulating biomarkers of inflammation or C-peptide, respectively. We used multivariable-adjusted Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for type I endometrial cancer risk. Results We documented 1462 type I endometrial cancer cases over 2 823 221 person-years of follow-up. In the pooled multivariable-adjusted analyses, women in the highest compared with lowest quintiles were at higher risk of type I endometrial cancer (EDIP HRQ5vsQ1 = 1.46, 95% CI = 1.24 to 1.73; P trend <.001; EDIH HRQ5vsQ1 = 1.58, 95% CI = 1.34 to 1.87; P trend <.001). Additional adjustment for body mass index attenuated the associations (EDIP HR = 1.03, 95% CI = 0.87 to 1.22; EDIH HR = 1.01, 95% CI = 0.85 to 1.21), and mediation analyses showed that body mass index may explain 60.4% (95% CI = 37.4% to 79.6%; P <.001) and 71.8% (95% CI = 41.0% to 90.4%; P <.001) of the association of endometrial cancer with EDIP and EDIH, respectively. Conclusions In this large cohort study, higher dietary inflammatory and insulinemic potential were each associated with increased endometrial cancer incidence, and this association may be almost entirely mediated by adiposity. [ABSTRACT FROM AUTHOR]

To determine associations between adoption of Medicaid expansion (ME) and changes in insurance status, early stage diagnosis, and cancer survival among women with endometrial carcinoma (EC). The National Cancer Database (NCDB) was queried for patients diagnosed with EC between the age 40–64 from 2004 to 2015. Difference-in-differences analysis quantified the impact of ME on the proportion of new EC diagnoses with insurance (vs. uninsured), the proportion diagnosed with stage I (vs. II-IV), and overall survival. 156,253 patients were included. Among 65,019 women living in ME states, ME is associated with an increase in the percent of EC cases who are insured of 1.4% (95% CI 0.9–2.0%, p < 0.0001), with strongest effects among Hispanic women, women in the lowest income quartile, and women in the second age quartile (age 53–57). There was no overall impact of ME on stage, though an increase of early stage diagnoses by 2.4% (95% CI 0.3–4.5%, p = 0.022) was observed among women age 53–57. There was a trend towards improved overall survival with ME, which was strongest in women age 53–57 (HR = 0.83, 95% CI 0.70–0.99, p = 0.037). Among women with EC, ME positively impacted insurance coverage, an important hurdle in accessing health care. In women aged 53–57, ME was associated with earlier stage at diagnosis and improved survival, suggesting that the magnitude of the improvement in insurance coverage may correlate with important clinical outcomes. Efforts should continue to understand the complexity of barriers to health care access and to develop effective strategies to surmount them. • Medicaid expansion improves insurance coverage for endometrial cancer patients. • Expansion improves coverage to a larger extent for some groups. • Some groups that experience a larger increase in coverage present at earlier stage. [ABSTRACT FROM AUTHOR]

Background Women with endometrial cancer (EC) are the second largest population of female cancer survivors in the United States. However, the outcomes of EC survivors, from the patient perspective, are not well-understood. Therefore, we conducted a systematic review of patient-reported outcomes (PROs) following an EC diagnosis. Methods We searched MEDLINE, EMBASE, Scopus, CINAHL, and reference lists to identify published observational studies that examined PROs among women with EC. Reviewers independently reviewed eligible full-text study articles and conducted data extraction. We qualitatively summarized included articles according to exposures [e.g. body mass index (BMI), treatment, etc.] or specific PROs (e.g. sexual function). Results Of 1722 unique studies, 102 full-text articles were reviewed, of which a total of 27 studies fulfilled the inclusion criteria. The most commonly used PRO questionnaires were the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) ( n = 9), Short Form 36 Questionnaire (SF-36, n = 8), the Functional Assessment of Cancer Therapy-General (FACT-G, n = 5), and the Female Sexual Function Index (FSFI, n = 4). Obesity was associated with lower quality of life (QOL) and physical functioning. Treatment type affected several outcomes. Laparoscopy generally resulted in better QOL outcomes than laparotomy. Likewise, vaginal brachytherapy was associated with better outcomes compared to external beam radiation. Sexual function outcomes were dependent on age, time since diagnosis, and having consulted a physician before engaging in sexual activities. In addition, a physical activity intervention was associated with improved sexual interest but not sexual function. Conclusions Our review provides insight into the experience of EC survivors from the patient perspective. Factors that contribute to QOL, such as pain, fatigue, emotional and social functioning, should be monitored following an EC diagnosis. [ABSTRACT FROM AUTHOR]

Background: Disparities in adjuvant treatment between Black and White women with endometrial cancer exist and contribute to worse outcomes among Black women. However, factors leading to disparate treatment receipt are understudied.Objective: We examined whether patient refusal of adjuvant treatment (chemotherapy or radiation) differed between Black and White women and whether treatment refusal mediated racial disparities in survival among women with endometrial cancer.Study Design: We used the National Cancer Database, a hospital-based cancer registry, to identify non-Hispanic Black and non-Hispanic White women diagnosed with endometrial cancer from 2004 to 2016 who either received or refused recommended radiation or chemotherapy. We used logistic regression to estimate multivariable-adjusted odds ratios and 95% confidence intervals for associations between race and treatment refusal. We also examined predictors of treatment refusal in race-specific models. Accelerated failure time models were used to estimate absolute differences in overall survival by race. We used causal mediation analysis to estimate the proportion of racial differences in overall survival attributable to racial differences in adjuvant treatment refusal. We considered the overall study population and strata defined by histology, and adjusted for sociodemographic, tumor, and facility characteristics.Results: Our analysis included 75,447 endometrial cancer patients recommended to receive radiation and 60,187 endometrial cancer patients recommended to receive chemotherapy, among which 6.4% and 11.4% refused treatment, respectively. Among Black women recommended for radiation or chemotherapy, 6.4% and 9.6% refused, respectively. Among White women recommended for radiation or chemotherapy, 6.4% and 11.8% refused, respectively. After adjusting for sociodemographic variables, facility characteristics, and tumor characteristics, Black women were more likely to refuse chemotherapy than White women (adjusted odds ratio, 1.26; 95% confidence interval, 1.15-1.37), but no difference in radiation refusal was observed (adjusted odds ratio, 1.00; 95% confidence interval, 0.91-1.11). Some predictors of radiation refusal varied by race, namely income, education, histology, stage, and chemotherapy receipt (P interactions<.05), whereas predictors of chemotherapy refusal were generally similar between Black and White women. Among women recommended for radiation, Black women survived an average of 4.3 years shorter than White women, which did not seem attributable to differences in radiation refusal. Among women recommended for chemotherapy, Black women survived an average of 3.2 years shorter than White women of which 1.9 months (4.9%) could potentially be attributed to differences in chemotherapy refusal.Conclusion: We observed differences in chemotherapy refusal by race, and those differences may be responsible for up to about 2 months of the overall 3.2-year survival disparity between White and Black women. Radiation refusal did not explain any of the 4.3-year disparity among women recommended for radiation. Treatment refusal accounts for, at most, a small fraction of the total racial disparity in endometrial cancer survival. Although a better understanding of the reasons for patient treatment refusal and subsequent intervention may help improve outcomes for some women, other causes of disparate outcomes, particularly those reflecting the social determinants of health, must be investigated. [ABSTRACT FROM AUTHOR]

Disparities in adjuvant treatment between Black and White women with endometrial cancer (EC) are well documented and contribute to worse outcomes among Black women. However, factors leading to disparate treatment patterns are understudied. We examined whether patient refusal of adjuvant treatment (chemotherapy or radiation) differed between Black and White women and whether refusal differences mediate racial disparities in EC survival. We used the National Cancer Database (NCDB), a hospital-based registry covering ~70% of U.S. cancer diagnoses, to identify non-Hispanic Black (NHB) and non-Hispanic White (NHW) women diagnosed with EC from 2004 to 2015 who either received or refused chemotherapy or radiation. NCDB data are abstracted from medical records by tumor registrars. We used logistic regression to estimate adjusted odds ratios (aOR) of patient refusal of treatment associated with race, and accelerated failure time models to estimate differences in overall survival (OS) by race. We used causal mediation analysis to estimate how much of the difference in OS by race could be attributed to racial differences in treatment refusal. We considered the overall study populations as well as strata defined by histology, and adjusted for factors assessed at diagnosis, including age, comorbidity burden, insurance, hospital characteristics, stage, histology, and zip code-level income and education. We identified 49,518 women (83% NHW, 17% NHB) who received adjuvant chemotherapy and 12,710 women with documented refusal (90% NHW, 10% NHB). After adjusting for covariates, NHB women were more likely to refuse chemotherapy than NHW women (aOR=1.12, p=0.005), particularly among those with low-grade endometrioid (aOR = 1.22, p=0.02) or serous (aOR = 1.38, p<0.001) EC. Mean OS for NHB women was 43.5 months shorter than for NHW women. Of this disparity, 0.9 months of may be attributable to differences in chemotherapy refusal (p=0.01). Among women with serous EC, NHB race was associated with 17.6 months shorter OS, with 1 month potentially attributable to refusal differences (p=0.002). We identified 66,839 women (88% NHW, 12% NHB) receiving adjuvant radiation and 4,471 (88% NHW, 12% NHB) who refused. Among women with serous EC, NHB women were more likely to refuse radiation (OR = 1.39, p=0.01), and NHB women had mean OS 13.2 months shorter than NHW women, 0.4 months of which may be attributable to differences in treatment refusal (p=0.03). We observed differences in treatment refusal by race, and those differences may be responsible for up to 1 month of the OS disparity between NHW and NHB women. This represents a small fraction of the dramatic racial disparity in EC survival. While a better understanding of the reasons for patient treatment refusal and subsequent intervention may help improve outcomes for some women, other causes of disparate outcomes warrant further investigation. [ABSTRACT FROM AUTHOR]