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.

Top advances of the year: Uterine cancer.

Endometrial cancer continues to be the only gynecologic malignancy with a rising incidence and mortality, with both regional and global implications. Combination carboplatin and paclitaxel has been the recognized chemotherapy backbone for the treatment of advanced-stage or recurrent disease, with modest clinical outcomes. Over the last year, significant advances were achieved in improving oncologic outcomes by capitalizing on the molecular characterization of this heterogenous disease. These advances include incorporation of immunotherapy, identification of effective hormonal approaches, the evolution of antibody drug conjugates, and utilization of alternate targeted therapies. PLAIN LANGUAGE SUMMARY: The molecular characterization of endometrial cancer has been critical in informing novel treatment strategies. Over the past year, significant gains have been made via the incorporation of immunotherapy, hormonal combinations as well as antibody drug conjugates.

Lynch Syndrome Genetics and Clinical Implications.

Lynch syndrome (LS) is one of the most prevalent hereditary cancer syndromes in humans and accounts for some 3% of unselected patients with colorectal or endometrial cancer and 10%-15% of those with DNA mismatch repair-deficient tumors. Previous studies have established the genetic basis of LS predisposition, but there have been significant advances recently in the understanding of the molecular pathogenesis of LS tumors, which has important implications in clinical management. At the same time, immunotherapy has revolutionized the treatment of advanced cancers with DNA mismatch repair defects. We aim to review the recent progress in the LS field and discuss how the accumulating epidemiologic, clinical, and molecular information has contributed to a more accurate and complete picture of LS, resulting in genotype- and immunologic subtype-specific strategies for surveillance, cancer prevention, and treatment.

Adding immunotherapy to first-line treatment of advanced and metastatic endometrial cancer.

BACKGROUND: Immunotherapy has transformed the endometrial cancer treatment landscape, particularly for those exhibiting mismatch repair deficiency [MMRd/microsatellite instability-hypermutated (MSI-H)]. A growing body of evidence supports the integration of immunotherapy with chemotherapy as a first-line treatment strategy. Recently, findings from ongoing trials such as RUBY (NCT03981796), NRG-GY018 (NCT03914612), AtTEnd (NCT03603184), and DUO-E (NCT04269200) have been disclosed. MATERIALS AND METHODS: This paper constitutes a review and meta-analysis of phase III trials investigating the role of immunotherapy in the first-line setting for advanced or recurrent endometrial cancer. RESULTS: The pooled data from 2320 patients across these trials substantiate the adoption of chemotherapy alongside immunotherapy, revealing a significant improvement in progression-free survival compared to chemotherapy alone [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.62-0.79] across all patient groups. Progression-free survival benefits are more pronounced in MMRd/MSI-H tumors (n = 563; HR 0.33, 95% CI 0.23-0.43). This benefit, albeit less robust, persists in the MMR-proficient/microsatellite stable group (n = 1757; HR 0.74, 95% CI 0.60-0.91). Pooled data further indicate that chemotherapy plus immunotherapy enhances overall survival compared to chemotherapy alone in all patients (HR 0.75, 95% CI 0.63-0.89). However, overall survival data maturity remains low. CONCLUSIONS: The incorporation of immunotherapy into the initial treatment for advanced and metastatic endometrial cancer brings about a substantial improvement in oncologic outcomes, especially within the MMRd/MSI-H subset. This specific subgroup is currently a focal point of investigation for evaluating the potential of chemotherapy-free regimens. Ongoing exploratory analyses aim to identify non-responding patients eligible for inclusion in clinical trials.

Pregnancy and obstetric outcomes after fertility-sparing management of endometrial cancer and atypical hyperplasia: a multicentre cohort study.

STUDY QUESTION: What are the pregnancy and obstetric outcomes in women with atypical hyperplasia (AH) or early-stage endometrial cancer (EC) managed conservatively for fertility preservation? SUMMARY ANSWER: The study found a live birth rate of 62% in patients with AH or EC after conservative treatment, with higher level of labour induction, caesarean section, and post-partum haemorrhage. WHAT IS KNOWN ALREADY: Fertility-sparing treatment is a viable option for women with AH or EC during childbearing years, but the outcomes of such treatments, especially regarding pregnancy and obstetrics, need further exploration. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study analysed data from January 2010 to October 2022, involving 269 patients from the French national register of patients with fertility-sparing management of AH/EC. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women above 18 years of age, previously diagnosed with AH/EC, and approved for fertility preservation were included. Patients were excluded if they were registered before 2010, if their treatment began <6 months before the study, or if no medical record on the pregnancy was available. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 95 pregnancies in 67 women were observed. Pregnancy was achieved using ART in 63 cases (66%) and the live birth rate was 62%, with early and late pregnancy loss at 26% and 5%, respectively. In the 59 cases resulting in a live birth, a full-term delivery occurred in 90% of cases; 36% of cases required labour induction and 39% of cases required a caesarean section. The most common maternal complications included gestational diabetes (17%) and post-partum haemorrhaging (20%). The average (±SD) birthweight was 3110 ± 736 g; there were no significant foetal malformations in the sample. No significant difference was found in pregnancy or obstetric outcomes between ART-obtained and spontaneous pregnancies. However, the incidence of induction of labour, caesarean section, and post-partum haemorrhage appears higher than in the general population. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of the study may introduce bias, and the sample size might be insufficient for assessing rare obstetric complications. WIDER IMPLICATIONS OF THE FINDINGS: This study offers valuable insights for healthcare providers to guide patients who received fertility-sparing treatments for AH/EC. These pregnancies can be successful and with an acceptable live birth rate, but they seem to be managed with caution, leading to possible tendency for more caesarean sections and labour inductions. No increase in adverse obstetric outcomes was observed, with the exception of suspicion of a higher risk of post-partum haemorrhaging, to be confirmed. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Neuroendocrine carcinoma of the endometrium: a retrospective analysis of data from a single center.

BACKGROUND: Neuroendocrine carcinoma (NEC) originating from the endometrium is rare, and there is limited knowledge regarding its diagnosis and optimal management. In this study, we present our experience with 11 patients with endometrial NEC, aiming to provide guidance for clinical practice. METHODS: We retrospectively collected the clinical, pathological, and treatment data of 11 patients with endometrial NEC who were treated at the First Affiliated Hospital of Zhengzhou University from January 2011 to July 2023. The clinicopathological characteristics, treatment and prognosis of these patients were analyzed. RESULTS: The median age of the patients was 55.0 (39.0-64.0) years, and the median tumor size was 40.0 (33.0-60.0) mm. Irregular vaginal bleeding was the most common symptom observed in 10 out of 11 patients, while metabolic syndrome occurred in only 2 out of 11 patients. Six out of the 11 patients were diagnosed at an early stage. Among the patients, 6 were diagnosed with endometrial NECs, while the remaining patients had a combination of endometrial NEC and other non-NEC endometrial carcinomas. All patients underwent surgery, except for one who received only chemotherapy due to multiple metastases. After surgery, adjuvant chemotherapy was administered to 5 patients, chemotherapy combined with radiotherapy was given to 3 patients, and 2 patients did not receive any adjuvant therapy. A total of 10 patients completed the follow-up, with a median follow-up time of 51.0 (14.3-81.0) months. Unfortunately, 2 patients died from the disease. CONCLUSION: NECs originating from the endometrium might not be affected by metabolic disorders. Preoperative diagnosis of these tumors was challenging. The primary approach for managing endometrial NEC can be multimodal treatment centered around surgery.

Potential of molecular classification to guide fertility-sparing management among young patients with endometrial cancer.

The traditional histological classification system for endometrial carcinoma falls short in addressing the disease's molecular heterogeneity, prompting the need for alternative stratification methods. Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) has emerged as a clinically efficient tool to categorize endometrial cancers according to mismatch repair deficiency, POLE exonuclease domain mutations, and p53 expression. However, the application of this classification to fertility-sparing treatments remains unexplored, and current guidelines lack specificity in how it should be used. In this review, we summarize the available literature and establish the framework for future investigations focused on molecular profiling-based risk assessment of endometrial cancer, with the goal of utilizing precision medicine to optimally counsel patients seeking fertility-sparing treatment. While the available evidence is limited and of low quality, it does provide insights and frames future perspectives for managing fertility-sparing approaches on the basis of molecular subtypes. Evidence suggests that mismatch repair-deficient tumors are likely to recur despite progestin therapy, emphasizing the need for alternative treatments, with targeted therapies being a new landscape that still needs to be explored. Tumors with POLE mutations exhibit a favorable prognosis, but the safety of hysteroscopic resection alone requires further investigation. p53 abnormal tumors have an unfavorable prognosis, raising questions about their suitability for fertility-sparing treatment. Lastly, the no specific molecular profile (or p53 wild-type) tumors, while having a relatively good prognosis, are heterogeneous and require more precise biomarkers to effectively guide therapy for those with poorer prognoses. Addressing these research gaps will lead to more precise guidelines to ensure optimal selection for fertility-sparing treatment.

Impact of different follow-up regimens on health-related quality of life and costs in endometrial cancer patients: Results from the TOTEM randomized trial.

PURPOSE: To investigate whether intensive follow-up (INT) after surgery for endometrial cancer impact health-related quality of life (HRQoL) and healthcare costs compared to minimalist follow-up (MIN), in the absence of evidence supporting any benefit on 5-year overall survival. METHODS: In the TOTEM trial, HRQoL was assessed using the SF-12 and the Psychological General Well-Being (PGWB) questionnaires at baseline, after 6 and 12 months and then annually up to 5 years of follow-up. Costs were analyzed after 4 years of follow-up from a National Health Service perspective, stratified by risk level. The probability of missing data was analyzed for both endpoints. RESULTS: 1847 patients were included in the analyses. The probability of missing data was not influenced by the study arms (MIN vs INT OR: 0.97 95%CI: 0.87-1.08). Longitudinal changes in HRQoL scores did not differ between the two follow-up regimens (MIN vs INT SF-12 PCS: -0.573, CI95%: -1.31; 0.16; SF-12 MCS: -0.243, CI95%: -1.08; 0.59; PGWB: -0.057, CI95%: -0,88; 0,77). The mean cost difference between the intensive and minimalist arm was €531 for low-risk patients and €683 for high-risk patients. CONCLUSION: In the follow-up of endometrial cancer after surgery, a minimalist treatment regimen did not affect quality of life and was cost-saving in both low-risk and high-risk recurrence patients. As previous results showed no survival benefit, a minimalist approach is justified. The relevant proportion of missing data on secondary outcomes of interest could be a critical point that deserves special attention.

Reduced healthcare access contributes to delay of care in endometrial cancer.

OBJECTIVE: We aimed to characterize delays to care in patients with endometrioid endometrial cancer and the role healthcare access plays in these delays. METHODS: A chart review was performed of patients with endometrioid endometrial cancer who presented with postmenopausal bleeding at a diverse, urban medical center between 2006 and 2018. The time from symptom onset to treatment was abstracted from the medical record. This interval was subdivided to assess for delay to presentation, delay to diagnosis, and delay to treatment. RESULTS: We identified 484 patients who met the inclusion criteria. The median time from symptom onset to treatment was 4 months with an interquartile range of 2 to 8 months. Most patients had stage I disease at diagnosis (88.6%). There was no significant difference in race/ethnicity or disease stage at time of diagnosis between different groups. Patients who had not seen a primary care physician or general obstetrician-gynecologist in the year before symptom onset were more likely to have significantly delayed care (27.7% vs 14.3%, p = 0.02) and extrauterine disease (20.2% vs 4.9%, p < 0.01) compared to those with established care. Black and Hispanic patients were more likely to experience significant delays from initial biopsy to diagnosis. CONCLUSIONS: Delays exist in the evaluation of endometrial cancer. This delay is most pronounced in patients without an established outpatient primary care provider or obstetrician-gynecologist.

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.

Racial disparities in endometrial cancer: Where are we after 26 years?

INTRODUCTION: Endometrial cancer is the most commonly diagnosed female genital tract malignancy in the United States of America. Racial disparities surrounding this particular disease have been extensively investigated for over 26-years. We sought to determine if research in this area has led to any significant improvements in this disparity. METHODS: We performed a rapid systematic review of English language publications on racial disparities in endometrial cancer among African American (AAW) and white American women (WAW), from 1997 to 2023. We looked at trends in incidence and survival; impact of known poor prognostic factors (stage at diagnosis, histological subtypes, grade); co-morbidities; differences in treatment (surgery, radiation and chemotherapy); socioeconomic factors; differences in biological and genetic markers; and policies/declarations. RESULTS: During the period under review (1997-2023), there was a notable increase in both disease incidence (39%) and mortality (26%) rates for AAW, in comparison to WAW among whom the incidence rates increased by 2% and mortality rates rose, but 9% less than for AAW. It should be noted that the current incidence rate of 29.4% in AAW represent a reversal of what is was 26-years ago, when the incidence rate was 17.8%. In comparison to WAW, AAW had a higher prevalence of poor prognostic variables, more co-morbidities, lower income levels, less insurance coverage, and were more frequently under treated with surgery, chemotherapy and radiation. To date no actionable molecular/genetic markers have been identified. We were unable to locate any published recommendations or active programs of implementation strategies/policies designed to effectively mitigate the documented racial disparity. CONCLUSION: Racial disparities in disease incidence and mortality in endometrial cancer rates between WAW and AAW have widened during a 26-year period of robust research, suggesting that current research alone is not enough to eliminate this disparity. Based on this rapid systematic review we have identified and analyzed the impact of causation variables on this disparity. Additionally, we have made strong and pertinent recommendations for the benefit of mitigating this escalating racial disparity.

Mixed-method approach to informing a lifestyle intervention to improve the survivorship of patients with endometrial cancer.

OBJECTIVES: To identify endometrial cancer survivors' (ECS) barriers and facilitators for participation in lifestyle interventions to improve their dietary and exercise behaviors. Our secondary objective is to determine baseline information: physical activity level, quality of life (QoL), and impact of COVID-19 on exercise, diet, and mental health. METHODS: Obese, early-stage ECS participated in 2-part mixed-methods data collection; Part 1: survey gathering sample characteristics, QoL, exercise, and basic endometrial cancer- related knowledge. Part 2: virtual focus group or individual interviews using a brainwriting premortem protocol. Statistical analysis was performed using SAS (version 8.3). Qualitative data were analyzed using deductive thematic coding guided by the RE-AIM framework. RESULTS: Twenty percent (70/358) of ECS from a survivorship database and clinic recruitment completed the survey; 16 ECS provided qualitative feedback. Common barriers to intervention participation included time and resource costs, meeting frequency, and pessimism about weight loss maintenance. Facilitators included an opportunity to connect with other survivors and a focus on health rather than weight loss. Most ECS could not identify exercise guidelines (60%) and 83% were not meeting these guidelines. Higher BMI was correlated with a lower confidence in completing in moderate physical activity (p-value = 0.0206). Post-COVID-19 pandemic, physical activity, nutritional decisions, and/or mental health worsened for 67% of ECS. CONCLUSION: ECS are a disparate population, with worsening behaviors and mental health following the pandemic. The identified ECS-specific barriers and facilitators to behavioral intervention participation are being used to simultaneously improve the reach of and adherence to a lifestyle intervention aimed at improving their health and QoL.

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.

Healthcare utilization in women diagnosed with endometrial cancer: A survey-based study.

OBJECTIVE: Despite similar incidence, non-Hispanic Black women are twice as likely to die of endometrial cancer as non-Hispanic White women. The social determinants of health may contribute to this disparity. We studied barriers to care and social needs of endometrial cancer patients. METHODS: In a cohort of patients with endometrial cancer from the All of Us study, participants self-reported demographics and completed validated surveys (access to medical care, transportation, caregiving, finances, medication, general care, specialty care, housing insecurity). Univariate and multivariate logistic regression models evaluated demographic and access factors associated with any need. RESULTS: Of 568 participants, 77.7% identified as non-Hispanic White, 7.5% Black, and 8.8% Hispanic. 59% were > 65 years and 95.8% insured. Contributors to delays in care were paying out of pocket (9.9%), provider anxiety (7.6%), transportation (6.3%), cost of copay (6.2%), and insufficient leave from work (5.6%). To mitigate healthcare costs, 16.2% of participants inquired about lower-cost medications, 11.1% reported delaying filling prescriptions, 7.6% taking fewer prescribed medications, and 6.5% skipped doses. Regarding multivariate analysis, participants earning <$25,000 had a 7.3 (95% CI 1.7-31.7) higher adjusted odds of transportation needs and 3.6 (95% CI 1.4-9.7) higher difficulty accessing specialists. No racial/ethnic disparities were identified. CONCLUSIONS: Social needs and barriers to care are most pronounced among endometrial cancer survivors earning <$25,000. Unexpectedly, and possibly related to sample size or survey tool, race/ethnicity were not zassociated with barriers to care. Further studies on health-related social needs, optimal screening tools, and effective interventions are needed in order to achieve equity in cancer outcomes for endometrial cancer patients.

Moving into the modern era of molecular classification for endometrial cancer.

The molecular subtypes of endometrial carcinoma (EC) were first described by The Cancer Genome Atlas (TCGA) a decade ago. Using surrogate approaches, the molecular classification has been demonstrated to be prognostic across EC patients and to have predictive implications. Starting in 2020, the molecular classification has been incorporated into multiple guidelines as part of the risk assessment and most recently into the International Federation of Gynecology and Obstetrics (FIGO) staging. This review article discusses the implementation of the EC molecular classification into clinical practice, the therapeutic implications, and the molecular and clinical heterogeneity of the EC molecular subtypes.

Reanalysis of single-cell data reveals macrophage subsets associated with the immunotherapy response and prognosis of patients with endometrial cancer.

Endometrial cancer (EC) is an aggressive gynecological malignancy with an increased incidence rate. The immune landscape crucially affects immunotherapy efficacy and prognosis in EC patients. Here, we characterized the distinct tumor microenvironment signatures of EC tumors by analyzing single-cell RNA sequencing data from Gene Expression Omnibus and bulk RNA sequencing data from The Cancer Genome Atlas, which were compared with normal endometrium. Three macrophage subsets were identified, and two of them showed tissue-specific distribution. One of the macrophage subsets was dominant in macrophages derived from EC and exhibited characteristic behaviors such as promoting tumor growth and metastasis. One of the other macrophage subsets was mainly found in normal endometrium and served functions related to antigen presentation. We also identified a macrophage subset that was found in both EC and normal endometrial tissue. However, the pathway and cellular cross-talk of this subset were completely different based on the respective origin, suggesting a tumor-related differentiation mechanism of macrophages. Additionally, the tumor-enriched macrophage subset was found to predict immunotherapy responses in EC. Notably, we selected six genes from macrophage subset markers that could predict the survival of EC patients, SCL8A1, TXN, ANXA5, CST3, CD74 and NANS, and constructed a prognostic signature. To verify the signature, we identified immunohistochemistry for the tumor samples of 83 EC patients based on the selected genes and further followed up with the survival of the patients. Our results provide strong evidence that the signature can effectively predict the prognosis of EC patients.

Favorable Outcome of High-grade Endometrial Stromal Sarcoma in an Adolescent.

High-grade endometrial stromal sarcoma is a rare and aggressive soft tissue tumor characterized by YWHAE::NUTM2A/B translocations, diagnosis at a median of 50-60 years, and a poor prognosis (overall survival 30%-40%). We describe a 16-year-old patient with high-grade endometrial stromal sarcoma and regional nodal and pulmonary metastases who is a long-term survivor after grossly complete tumor resection, intensive chemotherapy, and pelvic radiotherapy. We discovered a previously undescribed YWHAE::NUTM2E translocation in the tumor. Our patient's favorable outcome suggests that intensive multimodality therapy with curative intent is appropriate for young patients with high-grade endometrial stromal sarcoma and highlights the importance of fertility preservation.

Management of endometrial cancer in Latin America: raising the standard of care and optimizing outcomes.

Molecular characterization of endometrial cancer is allowing for increased understanding of the natural history of tumors and paving a more solid pathway for novel therapies. It is becoming increasingly apparent that molecular classification is superior to histological classification in terms of reproducibility and prognostic discrimination. In particular, the Proactive Molecular Risk Classifier for Endometrial Cancer allows classification of endometrial cancer into groups very close to those determined by the Cancer Genome Atlas Research Network-that is, DNA polymerase epsilon-mutated, mismatch repair-deficient, p53 abnormal, and non-specific molecular profile tumors. The transition from the chemotherapy era to the age of targeted agents and immunotherapy, which started later in endometrial cancer than in many other tumor types, requires widespread availability of specialized pathology and access to novel agents. Likewise, surgical expertise and state-of-the-art radiotherapy modalities are required to ensure adequate care. Nevertheless, Latin American countries still face considerable barriers to implementation of international guidelines. As we witness the dawn of precision medicine as applied to endometrial cancer, we must make continued efforts towards improving the quality of care in this region. The current article discusses some of these challenges and possible solutions.

Delivery of hereditary cancer genetics services to patients newly diagnosed with ovarian and endometrial cancers at three gynecologic oncology clinics in the USA, Brazil, and Mexico.

OBJECTIVE: Three gynecologic oncology clinics located in the USA, Brazil, and Mexico collaborated to evaluate their delivery of hereditary cancer genetics services. This descriptive retrospective review study aimed to establish baseline rates and timeliness of guideline-recommended genetics service delivery to patients with ovarian, fallopian tube, primary peritoneal (ovarian), and endometrial cancers at each clinic. METHODS: Patients who were newly diagnosed with ovarian and endometrial cancers between September 1, 2018 and December 31, 2020 were identified from the medical records of the clinics. Genetics service delivery metrics included the rates of mismatch repair deficiency tumor testing for patients with endometrial cancer (microsatellite instability/immunohistochemistry, MSI/IHC), referral to genetics services for patients with ovarian cancer, completed genetics consultations, and germline genetic testing for patients with ovarian and endometrial cancers. Timeliness was calculated as the average number of days between diagnosis and the relevant delivery metric. Descriptive statistics were used to analyze data. RESULTS: In total, 1195 patients (596 with ovarian cancer, 599 with endometrial cancer) were included in the analysis, and rates of genetics service delivery varied by clinic. For patients with ovarian cancer, referral rates ranged by clinic from 32.6% to 89.5%; 30.4-65.1% of patients completed genetics consultation and 32.6-68.7% completed genetic testing. The timeliness to genetic testing for patients with ovarian cancer ranged by clinic from 107 to 595 days. A smaller proportion of patients with endometrial cancer completed MSI/IHC testing (10.0-69.2%), with the average time to MSI/IHC ranging from 15 to 282 days. Rates of genetics consultation among patients with endometrial cancer ranged by clinic from 10.8% to 26.0% and 12.5-16.6% completed genetic testing. CONCLUSIONS: All clinics successfully established baseline rates and timeliness of delivering hereditary cancer genetics services to patients with ovarian and endometrial cancers. Lower rates of delivering genetics services to patients with endometrial cancer warrant additional research and quality improvement efforts.