Current recommendations and recent progress in endometrial cancer.

Endometrial cancer is the most common gynecologic cancer in the United States, and its incidence is rising. Although there have been significant recent advances in our understanding of endometrial cancer biology, many aspects of treatment remain mired in controversy, including the role of surgical lymph node assessment and the selection of patients for adjuvant radiation or chemotherapy. For the subset of women with microsatellite-instable, metastatic disease, anti- programmed cell death protein 1 immunotherapy (pembrolizumab) is now approved by the US Food and Drug Administration, and numerous trials are attempting to build on this early success.

Alterations of UHRF family Expression and was regulated by High Risk Type HPV16 in Uterine Cervical Cancer.

The altered protein expression of inverted CCAAT box-binding protein of 90 kDa/ubiquitin-like with PHD and RING finger domains 1 (ICBP90/UHRF1), and Np95-like ring finger protein (NIRF)/UHRF2, which belong to the ubiquitin-like with PHD and RING finger domains (UHRF) family, is linked to tumor malignancy and the progression of various cancers. In this study, we analyzed the UHRF family expression in cervical cancers, and it's regulation by human papillomavirus (HPV). Western blotting was performed to analyze protein expression in cervical cancer cell lines. Immunohistochemical analysis were used to investigate the expression of UHRF family and MIB-1 in cervical cancer tissues. Transfection were done for analyze the relationship between UHRF family and HPVs. We showed that NIRF expression was decreased and ICBP90 expression was increased in cervical cancers compared to normal counterparts. Western blotting also showed that NIRF expression was quite low levels, but ICBP90 was high in human cervical cancer cell lines. Interestingly, ICBP90 was up regulated by high risk type HPV16 E6 and E7, but not low-risk type HPV11. On the other hand, NIRF was down regulated by high risk type HPV16 E6 but not by E7. Low risk type HPV11 E6 did not affect the NIRF expression at all. We propose that ICBP90 overexpression, and reduced NIRF expression, found in cervical cancers, is an important event of a cervical carcinogenesis, and especially ICBP90 may offer a proliferating marker and therapeutic target for treating uterine cervical cancers.

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.

Association between adherence to posttreatment National Comprehensive Cancer Network (NCCN) surveillance guidelines and detection of recurrent uterine cancer.

OBJECTIVE: To identify correlations between disease recurrence and adherence to NCCN posttreatment surveillance guidelines in patients who develop recurrent uterine cancer. METHODS: Retrospective analysis identified patients (n = 60) with recurrent uterine cancer and at least one surveillance visit with a gynecologic oncologist between 2011 and 2020. Adherence to NCCN guidelines and details of recurrence were recorded. RESULTS: Recurrent uterine cancer was identified in 60 patients with an average time to recurrence (TTR) of 25 months. Of those, 39 (65%) were adherent to NCCN surveillance guidelines and 36 (60%) were symptomatic at the time of recurrence diagnosis. Asymptomatic recurrence was diagnosed by imaging in 11 (46%), physical exam in 7 (29%), and blood work in 6 (25%) patients. Patients who were adherent to NCCN guidelines were diagnosed with recurrence on average 11 months earlier (p = 0.0336). Adherence was an independent predictor of TTR for all patients regardless of symptoms. There was no significant effect of age, race, primary language, or stage of disease on adherence. CONCLUSION: Adherence to NCCN posttreatment surveillance guidelines for uterine cancer is independently associated with an earlier diagnosis of recurrence.

Black-White differences in uterine cancer symptomatology and stage at diagnosis.

OBJECTIVE: To examine whether uterine cancer symptoms differ between Black and White patients and how this may influence their stage at diagnosis. METHODS: Using the Surveillance, Epidemiology and End Results-Medicare database, we identified 2328 Black and 21,774 White patients with uterine cancer in 2008-2017. Their symptoms in the 18 months before diagnosis were categorized as postmenopausal bleeding (PMB) alone, PMB together with other symptoms (e.g., abdominal/pelvic pain, bloating), non-PMB symptoms alone, or no symptoms. Stage at diagnosis was dichotomized as advanced (i.e., regional/distant) versus localized. The association between race and stage was analyzed using regression models incrementally adjusting for symptoms and other patient characteristics. RESULTS: A larger proportion of Black than White patients experienced PMB together with other symptoms (63.1% versus 58.0%) or experienced non-PMB symptoms alone (13.1% versus 9.4%) (p < 0.001). Black patients had a higher risk of advanced-stage diagnosis than White patients (45.0% versus 30.3%, unadjusted RR = 1.52, 95% CI: 1.44-1.59). Adjusting for Black-White differences in symptoms attenuated the RR to 1.46 (95% CI: 1.39-1.53). Compared to PMB symptoms alone, having additional non-PMB symptoms (RR = 1.21, 95% CI: 1.15-1.26) and having non-PMB symptoms alone (RR = 1.99, 95% CI: 1.88-2.10) were associated with increased risk of advanced-stage diagnosis. Further adjusting for histology and other patient characteristics reduced Black-White disparity in advanced-stage diagnosis to 1.08 (95% CI: 1.03-1.14) but symptoms remained significantly associated with stage at diagnosis. CONCLUSIONS: Having non-PMB symptoms was associated with more advanced stage at diagnosis. Non-PMB symptoms were more common among Black than White patients, which might hinder symptom recognition/evaluation.

Exploring the perspectives of underrepresented voices: Perceptions and experiences of uterine cancer for black African, Caribbean, black British, and mixed-black women in the UK to develop strategies for early symptom presentation.

OBJECTIVES: The uterine cancer (UC) mortality rate in the UK is significantly higher for women who belong to a Black ethnic group compared to those from other ethnic groups. This study aimed to understand the views and experiences of UC amongst Black ethnic minority women in the UK, with a focus on awareness and presentation of red-flag symptoms. METHODS: Women of Black African, Caribbean, Black British and Mixed-Black ethnicity were purposefully recruited to participate in focus groups and individual semi-structured interviews. RESULTS: Twenty women from different regions in England participated in the study. Reflexive thematic analysis of the data led to the identification of three main themes: 1) Healthcare inequities; 2) Support and sense making with other Black women; and 3) Knowledge dissemination, mobilisation, and empowerment. Perceptions of inequitable healthcare provision and distrust influenced how participants, and their peer networks, approached seeking assistance from healthcare professionals. Concerns were also raised about culturally insensitive information resources, including issues of language, literacy, and representation, all of which served as potential barriers for women within Black ethnic minority groups. CONCLUSIONS: The deficiency of targeted knowledge mobilisation and specific UC information aimed at Black ethnicity women living in the UK, reportedly contributes to the dissemination of misconceptions and an atmosphere of apprehension around a UC diagnosis. The insights from this study highlight the significance of designing culturally sensitive strategies to promote informed decision-making and empower the dissemination of accurate health knowledge amongst Black women.

Trends in uterine cancer incidence in the United States: The contribution of age, period and cohort effects.

OBJECTIVE: In the U.S., uterine cancer incidence is rising, with racial and ethnic minorities experiencing the largest increases. We performed age-period-cohort analyses using novel methods to examine the contribution of age at diagnosis (age), year of diagnosis (period), and birth cohort (cohort), to trends in uterine cancer incidence. METHODS: We used uterine cancer incidence data from the Surveillance, Epidemiology, and End Result (SEER) 12 database (1992-2019), and performed hysterectomy-correction. We generated hexamaps to visualize age, period, and cohort effects, and used mutual information to estimate the percent contribution of age, period, and cohort effects, individually and combined, on uterine cancer incidence, overall and by race and ethnicity and histology. RESULTS: Hexamaps showed an increase in uterine cancer in later time periods, and a cohort effect around 1933 showing a lower incidence compared with earlier and later cohorts. Age, period, and cohort effects combined contributed 86.6% (95% CI: 86.4%, 86.9%) to the incidence. Age effects had the greatest contribution (65.1%, 95% CI: 64.3%, 65.9), followed by cohort (20.7%, 95% CI: 20.1%, 21.3%) and period (14.2%, 95% CI: 13.7%, 14.8%) effects. Hexamaps showed higher incidence in recent years for non-Hispanic Blacks and non-endometrioid tumors. CONCLUSIONS: Age effects had the largest contribution to uterine cancer incidence, followed by cohort and period effects overall and across racial and ethnic groups and histologies. IMPACT: These findings can inform uterine cancer modeling studies on the effects of interventions that target risk factors which may vary across age, period, or cohort.

Cost-effectiveness of lenvatinib plus pembrolizumab versus chemotherapy for recurrent mismatch repair-proficient endometrial cancer after platinum-based therapy.

OBJECTIVE: The recent Study 309-KEYNOTE-775 showed improved survival for lenvatinib plus pembrolizumab compared to chemotherapy in patients with recurrent endometrial cancer. We created a decision model to compare the cost-effectiveness of lenvatinib plus pembrolizumab in patients with recurrent mismatch repair-proficient (pMMR) endometrial cancer who had progressed after first-line chemotherapy. METHODS: A Markov model was created to simulate the clinical trajectory of 10,000 patients with recurrent pMMR endometrial cancer. The initial decision point in the model was treatment with ether lenvatinib plus pembrolizumab or chemotherapy (doxorubicin or dose-dense paclitaxel). Model probabilities, utility values and costs were derived with assumptions drawn from published literature. A cycle length of 3 months and a time horizon of 2 years was used. The effectiveness was calculated in terms of average quality adjusted life years (QALYs) gained. The primary outcome was incremental cost-effectiveness ratios (ICERs), expressed in 2020 US dollars/QALYs. One-way, two-way and probabilistic sensitivity analyses were performed. RESULTS: Chemotherapy was the least costly strategy at $66,693 followed by lenvatinib plus pembrolizumab ($193,590). Lenvatinib plus pembrolizumab resulted in more patients being alive at 2 years (lenvatinib plus pembrolizumab: 367, chemotherapy: 109). Chemotherapy was cost-effective compared with lenvatinib plus pembrolizumab (ICER: $164,493/QALYs). Lenvatinib plus pembrolizumab became cost-effective when its cost was reduced by $1553 per month (7.8% reduction). CONCLUSION: For patients with recurrent pMMR endometrial cancer Lenvatinib plus pembrolizumab is associated with greater survival but is more costly than chemotherapy. The cost of lenvatinib and pembrolizumab would have to be reduced by approximately 7% to be considered cost-effective.

Variation in telemedicine usage in gynecologic cancer: Are we widening or narrowing disparities?

INTRODUCTION: Telemedicine rapidly increased with the COVID-19 pandemic and could reduce cancer care disparities. Our objective was to evaluate sociodemographic (race, insurance), patient, health system, and cancer factors associated with telemedicine use in gynecologic cancers. METHODS: We conducted a retrospective cohort study of patients with endometrial cancer and epithelial ovarian cancer with at least one visit from March 2020 to October 2021, using a real-world electronic health record-derived database, representing approximately 800 sites in US academic (14%) and community practices (86%). We used multivariable Poisson regression modeling to analyze the association of ever using telemedicine with patient, sociodemographic, health system, and cancer factors. RESULTS: Of 3950 patients with ovarian cancer, 1119 (28.3%) had at least one telemedicine visit. Of 2510 patients with endometrial cancer, 720 (28.7%) had at least one telemedicine visit. At community cancer practices, patients who identified as Black were less likely to have a telemedicine visit than patients who identified as white in both ovarian and endometrial cancer (Ovarian: RR 0.62, 95% CI 0.42-0.9; Endometrial: RR 0.56, 95% CI 0.38-0.83). Patients in the Southeast, Midwest, West, and Puerto Rico were less likely to have telemedicine visits than patients in the Northeast. Uninsured patients were less likely, and patients with Medicare were more likely, to have one or more telemedicine visit than patients with private insurance. CONCLUSIONS: In this national cohort study, <30% of patients ever used telemedicine, and significant racial and regional disparities existed in utilization. Telemedicine expansion efforts should include programs to improve equity in access to telemedicine.

Estrogen replacement therapy and non-hormonal medication use among patients with uterine cancer.

OBJECTIVE: As the prognosis for endometrial cancer is excellent, management of the effects of estrogen deprivation has an important influence on quality of life. We examined the trends in the use of estrogen replacement therapy (ERT) and non-hormonal medications among patients with uterine cancer following surgery. METHODS: The MarketScan Database was used to identify patients 18-49 years who underwent hysterectomy plus oophorectomy and those aged 50-75 years who underwent hysterectomy between 2008 and 2020. ERT and non-hormonal treatments of menopause were identified preoperatively and postoperatively. After propensity score balancing, difference-in-differences (DID) analyses were performed to compare the pre-and-postoperative changes in ERT and non-hormonal medication use between groups. The trends in postoperative use of ERT were assessed and tested using Cochran-Armitage trend tests. RESULTS: A total of 19,700 patients with uterine cancer and 185,150 controls were identified. Overall, postoperative ERT use decreased for both age groups and for patients with and without uterine cancer. The DID in ERT use between those with uterine cancer and those with benign pathology after hysterectomy was -37.1% (95% CI, -40.5 to -33.6%) for patients 18-49 years of age and - 10.4% (95% CI, -10.9 to -9.9%) for those 50-75 years. The DID for non-hormonal medication use between those with uterine cancer and those with benign pathology after hysterectomy was 11.2% (95% CI, 7.8 to 14.7%) for younger patients and 3.4% (95% CI, 2.9 to 4.0%) for those 50-75 years. The postoperative new ERT use has been declining over time in patients with uterine cancer in those 18-49 years of age (P = .02) and those 50-75 years of age (P < .001). CONCLUSIONS: The use of ERT is uncommon and has declined over time in patients with uterine cancer. Conversely, non-hormonal medications are more commonly used among patients with uterine cancer.

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.

Practice patterns, time trends and quality of care of uterine cancer in Belgium: An analysis of the EFFECT database.

OBJECTIVES: To investigate the practice patterns and quality of care for uterine cancer on a national level in Belgium, including trends in practice over the period 2012-2016. METHODS: Quality indicators were measured using the EFFectiveness of Endometrial Cancer Treatment (EFFECT) database. Multivariable logistic mixed regression was used to test for associations between the quality indicators and year of diagnosis, adjusted for potential confounders and intra-cluster correlations. RESULTS: The EFFECT database includes 4178 patients diagnosed with uterine cancer in the period 2012-2016. Minimally invasive surgery (laparoscopic or robotic-assisted) was applied in 61.6% of patients who had surgery for clinical stage I endometrial carcinoma (EC), increasing from 52.9% in 2012 to 66.4% in 2016. At least pelvic lymph node staging was performed in 69.0% of patients with clinical stage I, high-grade EC; and in 63.9% of patients with clinical stage I-II serous carcinoma, clear cell carcinoma or carcinosarcoma. The latter increased from 48.8% in 2012 to 77.2% in 2016. Adjuvant radiotherapy (external beam and/or brachytherapy) was offered to 33.5% of patients who had surgery without lymph node staging for pathological stage I EC at high-intermediate or high risk of recurrence. Adjuvant chemotherapy was administered to 64.4% of patients with pathological stage III-IVA EC. CONCLUSIONS: Study results indicate an overall good quality of care for patients with uterine cancer in Belgium. Treatment areas with potential room for improvement include the use of minimally invasive surgery, comprehensive surgical staging and adjuvant therapy, which confirms the remaining controversies in uterine cancer treatment and the need for further research.

Uterine Cancer Incidence Trends and Five-Year Relative Survival by Race/Ethnicity and Histology Among Women Under 50 Years.

BACKGROUND: Uterine cancers diagnosed before age 50 years are increasing in the U.S., but changes in clinical characteristics and survival over time across racial/ethnic groups have not been previously described. OBJECTIVES: To investigate age-adjusted, hysterectomy corrected incidence rates and trends, and five-year relative survival rates of uterine cancer in women aged <50 years, overall and stratified by race/ethnicity and histology. STUDY DESIGN: We included microscopically confirmed uterine cancer cases (diagnosed 2000-2019) in women aged 20-49 years from the Surveillance, Epidemiology, and End Results Program (SEER 22). Age-adjusted incidence and 5-year relative survival rates, and 95% confidence intervals were computed using SEER*Stat and compared across time periods (2000-2009 and 2010-2019). Incidence rates were adjusted for hysterectomy prevalence using Behavioral Risk Factor Surveillance System data, and trends were computed using the Joinpoint regression program. RESULTS: We included 57,128 uterine cancer cases. The incidence of uterine cancer increased from 10.1 per 100,000 in 2000-2009 to 12.0 per 100,000 in 2010-2019, increasing at an annual rate of 1.7%/year for the entire period. Rising trends were more pronounced among women <40 years (3.0%/year and 3.3%/year in 20-29 and 30-39 years, respectively) than in those 40-49 years (1.3%/year), and among underrepresented racial/ethnic groups (Hispanic 2.8%/year, Non-Hispanic, [NH]-Black 2.7%, NH-Asian/Pacific Islander [PI] 2.1%) than in NH-White (0.9%/ year). Recent (2010-2019) incidence rates were highest for endometrioid (9.6 per 100,000), followed by sarcomas (1.2), and non-endometrioid subtypes (0.9). Rates increased significantly for endometrioid subtypes at 1.9%/year from 2000-2019. Recent endometrioid and non-endometrioid rates were highest in NH-Native American/Alaska Native [NA/AN] (15.2 and 1.4 per 100,000), followed by Hispanic (10.9 and 1.0), NH-Asian/PI (10.2 and 0.9), NH-White (9.4 and 0.8), and lowest in NH-Black women (6.4 and 0.8). Sarcoma rates were highest in NH-Black women (1.8 per 100,000). The five-year relative survival remained unchanged over time for women with endometrioid (from 93.4% in 2000-2009 to 93.9% in 2010-2019, p≥0.05) and non-endometrioid subtypes (from 73.2% to 73.2%, p≥0.05) but decreased for women with sarcoma from 69.8% (2000-2009) to 66.4% (2010-2019, p<0.05). CONCLUSIONS: Uterine cancer incidence rates in women <50 years have increased from 2000 to 2019 while survival has remained relatively unchanged. Incidence trends can be primarily attributed to increasing rates of cancers with endometrioid histology, with the greatest increases observed among NH-Black, Hispanic, and NH-Asian/PI. Sarcomas, while much rarer, were the second most common type of uterine cancer among women <50 years and have poor prognosis and apparent decreasing survival over time. Rising rates of uterine cancer and the distinct epidemiologic patterns among women <50 years highlight the need for effective prevention and early detection strategies for uterine cancer in this age group.

Racial and ethnic differences in early death among gynecologic malignancy.

BACKGROUND: Racial and ethnic differences in early death after cancer diagnosis have not been well studied in gynecologic malignancy. OBJECTIVE: This study aimed to assess population-level trends and characteristics of early death among patients with gynecologic malignancy based on race and ethnicity in the United States. STUDY DESIGN: The National Cancer Institute's Surveillance, Epidemiology, and End Results Program was queried to examine 461,300 patients with gynecologic malignancies from 2000 to 2020, including uterine (n=242,709), tubo-ovarian (n=119,989), cervical (n=68,768), vulvar (n=22,991), and vaginal (n=6843) cancers. Early death, defined as a mortality event within 2 months of the index cancer diagnosis, was evaluated per race and ethnicity. RESULTS: At the cohort level, early death occurred in 21,569 patients (4.7%), including 10.5%, 5.5%, 2.9%, 2.5%, and 2.4% for tubo-ovarian, vaginal, cervical, uterine, and vulvar cancers, respectively (P<.001). In a race- and ethnicity-specific analysis, non-Hispanic Black patients with tubo-ovarian cancer had the highest early death rate (14.5%). Early death racial and ethnic differences were the largest in tubo-ovarian cancer (6.4% for Asian vs 14.5% for non-Hispanic Black), followed by uterine (1.6% for Asian vs 4.9% for non-Hispanic Black) and cervical (1.8% for Hispanic vs 3.8% to non-Hispanic Black) cancers (all, P<.001). In tubo-ovarian cancer, the early death rate decreased over time by 33% in non-Hispanic Black patients from 17.4% to 11.8% (adjusted odds ratio, 0.67; 95% confidence interval, 0.53-0.85) and 23% in non-Hispanic White patients from 12.3% to 9.5% (adjusted odds ratio, 0.77; 95% confidence interval, 0.71-0.85), respectively. The early death between-group difference diminished only modestly (12.3% vs 17.4% for 2000-2002 [adjusted odds ratio for non-Hispanic White vs non-Hispanic Black, 0.54; 95% confidence interval, 0.45-0.65] and 9.5% vs 11.8% for 2018-2020 [adjusted odds ratio, 0.65; 95% confidence interval, 0.54-0.78]). CONCLUSION: Overall, approximately 5% of patients with gynecologic malignancy died within the first 2 months from cancer diagnosis, and the early death rate exceeded 10% in non-Hispanic Black individuals with tubo-ovarian cancer. Although improving early death rates is encouraging, the difference among racial and ethnic groups remains significant, calling for further evaluation.

Evaluating equity of access and predictors of minimally invasive hysterectomy for endometrial and cervical cancer from 2000 to 2017 in Ontario, Canada: A population-based cohort study.

INTRODUCTION: We sought to assess the uptake of minimally invasive hysterectomy among patients with endometrial and cervical cancer in Ontario, Canada, and assess the equity of access to minimally invasive surgery (MIS) by evaluating associations with patient, disease, institutional, and provider factors. METHODS: This is a retrospective population-based cohort study of hysterectomy for endometrial and cervical cancer in Ontario (2000-2017). Surgical approach, clinicopathologic, sociodemographic, institutional, and provider factors were identified through administrative databases. Fisher's exact, χ2 , Wilcoxon rank sum, logistic regression, and Cox proportional hazards modeling were used to explore factors associated with MIS. RESULTS: A total of 27 652 patients were included. In total, 6199/24 264 (26%) endometrial and 842/3388 (25%) cervical cancer patients received MIS. The proportion of MIS to open surgeries increased from <0.1% in 2000 to over 55% in 2017 (odds ratio [OR] = 1.31, confidence interval [CI] = 1.28-1.34). Low-income quintile, rurality, low hospital volume, nonacademic hospital, nongynecologic oncology surgeon, and earlier year of surgeon graduation were associated with reduced odds of MIS (OR < 1). CONCLUSIONS: The uptake of MIS hysterectomy increased steadily over the time period. Receipt of MIS is dependent upon multiple social determinants, provider variables, and systems factors. These disparities raise concern for health equity in Ontario and have significant implications for health systems planning and resource allocation.

Antibody-Drug Conjugates in Gynecologic Cancers.

OPINION STATEMENT: Antibody-drug conjugates (ADCs) are a novel class of targeted cancer therapies with the ability to selectively deliver a cytotoxic drug to a tumor cell using a monoclonal antibody linked to a cytotoxic payload. The technology of ADCs allows for tumor-specificity, improved efficacy, and decreased toxicity compared to standard chemotherapy. Common toxicities associated with ADC use include ocular, pulmonary, hematologic, and neurologic toxicities. Several ADCs have been approved by the United States Food and Drug Administration (FDA) for the management of patients with recurrent or metastatic gynecologic cancers, a population with poor outcomes and limited effective treatment options. The first FDA-approved ADC for recurrent or metastatic cervical cancer was tisotumab vedotin, a tissue factor-targeting agent, after demonstrating response in the innovaTV 204 trial. Mirvetuximab soravtansine targets folate receptor alpha and is approved for use in patients with folate receptor alpha-positive, platinum-resistant, epithelial ovarian cancer based on results from the SORAYA trial. While there are no FDA-approved ADCs for the treatment of uterine cancer, trastuzumab deruxtecan, an anti-human epidermal growth factor receptor 2 (HER2) agent, is actively being investigated. In this review, we will describe the structure and mechanism of action of ADCs, discuss their toxicity profiles, review ADCs both approved and under investigation for the management of gynecologic cancers, and discuss mechanisms of ADC resistance.

Current Treatment Options: Uterine Sarcoma.

OPINION STATEMENT: The cornerstone of treatment for uterine sarcoma, regardless of histologic type, remains en bloc surgical resection with total hysterectomy. In the case of incidental diagnosis during another procedure, such as myomectomy, where a hysterectomy was not performed initially, completion hysterectomy or cervical remnant removal is recommended. The completion of additional surgical procedures, including bilateral salpingo-oophorectomy and lymphadenectomy, remains nuanced. Bilateral salpingo-oophorectomy remains controversial in the setting of most subtypes of uterine sarcoma, except in the case of hormone-receptor positivity, such as in low grade endometrial stromal sarcoma, where it is indicated as part of definitive surgical treatment. In the absence of apparent nodal involvement, we do not recommend performing universal lymphadenectomy for patients with sarcoma. We recommend systemic therapy for patients with extra-uterine or advanced stage disease, high-grade histology, and recurrence. The most active chemotherapy regimens for advanced, high-grade disease remain doxorubicin or gemcitabine and docetaxol combination therapy. A notable exception is low grade endometrial stromal sarcoma, where we recommend anti-hormonal therapy in the front-line setting. Radiation therapy is reserved for selected cases where it can aid in palliating symptoms.

Predictive value of SUVmax from initial 18F-FDG PET/CT scans for treatment outcomes in endometrial cancer patients undergoing fertility sparing management.

OBJECTIVE: To evaluate whether the maximum standardized uptake value (SUVmax) from initial 18F-FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) scans could be a predictor of complete response and recurrence in patients with endometrial cancer who are undergoing fertility sparing management. METHODS: We conducted a retrospective review of patients who were diagnosed with endometrial cancer through biopsy and chose to undergo fertility sparing management using progestin at the Asan Medical Center, from January 2011 to December 2020. Of these, 113 patients who had an 18-FDG-PET/CT scan before starting treatment were included in our study. We measured SUVmax and examined its correlation with complete response and time to progression after achieving complete response to progestin therapy. RESULTS: Of 113 patients, 73 (64.6%) achieved a complete response through fertility sparing management. The receiver operating characteristic curve analysis revealed that the optimal cut-off value of SUVmax for predicting complete response was 6.2 (sensitivity 79.5%, specificity 57.5%, p=0.006). After analyzing recurrence in the 73 patients who achieved complete response, we found that patients with an SUVmax value >6.2 had a significantly shorter time to progression compared with those with a value <6.2. (p=0.04). CONCLUSIONS: SUVmax values of PET-CT, along with other clinicopathological parameters, could be used to predict treatment response and recurrence risk in patients with stage I endometrial cancer undergoing fertility sparing management.

ENGOT-EN20/GOG-3083/XPORT-EC-042 - A phase III, randomized, placebo-controlled, double-blind, multicenter trial of selinexor in maintenance therapy after systemic therapy for patients with p53 wild-type, advanced, or recurrent endometrial carcinoma: rationale, methods, and trial design.

BACKGROUND: Patients with advanced/recurrent endometrial cancer have a poor prognosis and limited treatment options. Biomarkers such as tumor protein 53 (TP53) in endometrial cancer can integrate novel strategies for improved and individualized treatment that could impact patient outcomes. In an exploratory analysis of the phase III ENGOT-EN5/GOG-3055/SIENDO study of selinexor maintenance monotherapy 80 mg in advanced/recurrent endometrial cancer, a pre-specified subgroup of patients with TP53 wild type (wt) endometrial cancer showed preliminary activity at long-term follow-up with a generally manageable safety profile (median progression-free survival 27.4 months vs 5.2 months placebo, HR=0.41). PRIMARY OBJECTIVE: To evaluate the efficacy of selinexor compared with placebo as maintenance therapy in patients with advanced or recurrent TP53wt endometrial cancer. STUDY HYPOTHESIS: Selinexor administered at 60 mg weekly as maintenance therapy will show manageable safety and maintain efficacy in patients with TP53wt advanced/recurrent endometrial cancer after systemic therapy versus placebo. TRIAL DESIGN: This is a prospective, multicenter, double-blind, placebo-controlled, randomized phase III study designed to evaluate the efficacy and safety of selinexor as a maintenance therapy in patients with advanced or recurrent TP53wt endometrial cancer. MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients must have histologically confirmed endometrial cancer, TP53wt confirmed by next-generation sequencing, completed at least 12 weeks of platinum-based therapy with or without immunotherapy, with confirmed partial response or complete response, and primary Stage IV disease or at first relapse. PRIMARY ENDPOINT: The primary endpoint is investigator-assessed progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in the intent-to-treat population. SAMPLE SIZE: A total of 220 patients will be enrolled. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual is expected to be completed in 2024 with presentation of results in 2025. TRIAL REGISTRATION: NCT05611931.

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.