Reducing health disparities in endometrial cancer care in 2024.

PURPOSE OF REVIEW: To summarize the most recent publications explaining disparities among patients diagnosed with endometrial cancer and identify areas of improvement. RECENT FINDINGS: Racial disparities in endometrial cancer care have been identified along the cancer continuum including risk, diagnosis, access to treatment, and overall survival. The mortality gap in endometrial cancer is one of the top five widest Black-White mortality gaps among all cancer diagnoses in the United States. Many publications have demonstrated that the disparities exist, the aim of this review is to identify actionable areas of improvement. To mitigate racial disparities, we must acknowledge that Black patients are at higher risk of high-risk subtypes of endometrial cancer, and their presentation can vary from what is considered typical for the most common type of endometrial cancer. We must address that practice recommendations for diagnosis may not be generalizable to all races and ethnicities, and that racism has an impact on how providers approach a work-up for Black vs. White patients. Finally, we must improve access to appropriate treatment by steadfastly adhering to recommended practice guidelines regardless of race/ethnicity and improving efforts to enroll a diverse patient population to clinical trials. SUMMARY: In this review, we sought to identify specific and actionable areas of improvement to reduce racial disparities in endometrial cancer care.

TP53 mutation and abnormal p53 expression in endometrial cancer: Associations with race and outcomes.

OBJECTIVE: This multi-center cohort study assessed associations between race, TP53 mutations, p53 expression, and histology to investigate racial survival disparities in endometrial cancer (EC). METHODS: Black and White patients with advanced or recurrent EC with Next Generation Sequencing data in the Endometrial Cancer Molecularly Targeted Therapy Consortium database were identified. Clinicopathologic and treatment variables were summarized by race and compared. Overall survival (OS) and progression-free survival (PFS) among all patients were estimated by the Kaplan-Meier method. Cox proportional hazards models estimated the association between race, TP53 status, p53 expression, histology, and survival outcomes. RESULTS: Black patients were more likely than White patients to have TP53-mutated (N = 727, 71.7% vs 49.7%, p < 0.001) and p53-abnormal (N = 362, 71.1% vs 53.2%, p = 0.003) EC. Patients with TP53-mutated EC had worse PFS (HR 2.73 (95% CI 1.88-3.97)) and OS (HR 2.20 (95% CI 1.77-2.74)) compared to those with TP53-wildtype EC. Patients with p53-abnormal EC had worse PFS (HR 2.01 (95% CI 1.22-3.32)) and OS (HR 1.61 (95% CI 1.18-2.19)) compared to those with p53-wildtype EC. After adjusting for TP53 mutation and p53 expression, race was not associated with survival outcomes. The most frequent TP53 variants were at nucleotide positions R273 (n = 54), R248 (n = 38), and R175 (n = 23), rates of which did not differ by race. CONCLUSIONS: Black patients are more likely to have TP53-mutated and p53-abnormal EC, which are associated with worse survival outcomes than TP53- and p53-wildtype EC. The higher frequency of these subtypes among Black patients may contribute to survival disparities.

Impact of treatment modality on pelvic floor dysfunction among uterine cancer survivors.

OBJECTIVE: Pelvic floor dysfunction is a common adverse effect of uterine cancer treatment. In this study we compared patient-reported outcomes regarding pelvic floor dysfunction among uterine cancer survivors after hysterectomy and bilateral salpingo-oophorectomy, surgery and brachytherapy, or surgery and external beam radiotherapy with or without brachytherapy versus women who had a hysterectomy for benign indications. METHODS: We used the validated 20-item Pelvic Floor Distress Inventory to assess lower urinary distress, colorectal distress, and pelvic organ prolapse dysfunction in each treatment group. Pelvic floor dysfunction-related quality of life in these domains was compared across treatment modalities using the Pelvic Floor Impact Questionnaire-7. Treatment type, body mass index, comorbidities, and number of vaginal births were obtained from medical records. A zero-inflated negative binomial regression model was used to assess the association of treatment regimens and covariates relative to the non-cancer cohort. RESULTS: A total of 309 surveys were analyzed. The median age of the patients at surgery was 58 years (range 20-87) and the median age at survey completion was 66 years (range 34-92). Most participants reported experiencing at least one symptom of pelvic floor dysfunction (76% by Pelvic Floor Distress Inventory-2). The type of treatment had no effect on overall pelvic floor dysfunction on multivariate analysis (all p>0.05). Worse urinary-related symptoms were associated with higher body mass index at surgery (OR 1.41), higher age at time of survey (OR 1.07), and higher numbers of vaginal births (OR 1.43) (all p<0.05). CONCLUSIONS: Overall, pelvic floor dysfunction did not significantly vary by treatment modality. Our findings suggest complex interactions among age, body mass index, and parity as to how uterine cancer treatment affects pelvic floor quality of life, which should be considered in the choice of treatment strategy and patient counseling.

Incidence and Survival of Multiple Primary Cancers in US Women With a Gynecologic Cancer.

Objectives: To evaluate risk of a second cancer and associated survival times in United States women with diagnosis of cancer. Methods: The Surveillance Epidemiology and End Results (SEER) database was queried for 2 cohorts of women aged 18 - 89 with either an index gynecologic or non-gynecologic cancer diagnosed between 1992 - 2017. Index cases were followed to determine if a second primary cancer was subsequently diagnosed; defined according to SEER multiple primary and histology coding rules. Standard Incident Ratios (SIR) and latency intervals between index diagnosis and second primary diagnosis were evaluated. Among those who developed a second primary cancer, median survival times from diagnosis of second primary cancer were also calculated. Results: Between 1992 - 2017, 227,313 US women were diagnosed with an index gynecological cancer and 1,483,016 were diagnosed with an index non-gynecologic cancer. Among patients with index gynecologic cancer, 7.78% developed a non-gynecologic subsequent primary cancer. The risk of developing any non-gynecologic cancer following an index gynecologic cancer was higher than the risk in the general population (SIR 1.05, 95% CI 1.04 - 1.07). Organs especially at risk were Thyroid (SIR 1.45), Colon and Rectum (SIR 1.23), and Urinary System (SIR 1.33). Among women diagnosed with an index non-gynecologic cancer, 0.99% were diagnosed with a subsequent gynecologic cancer. The risk of developing a gynecologic cancer following a non-gynecologic cancer was also elevated compared to the average risk of the general population (SIR 1.05, 1.03 - 1.07), with uterine cancer having the highest SIR of 1.13. Conclusion: The risk of a developing a second primary cancer and the corresponding survival time is based on the order and site of the index and subsequent cancer. Surveillance guidelines should be examined further to optimize survivorship programs.

Tubal factor infertility and its impact on reproductive freedom of African American women.

In the past, the reproductive freedom of African American women was hindered by forced reproduction and sterilization campaigns. Unfortunately, these involuntary practices have now mostly been replaced by inequality because of disproportionate tubal factor infertility rates within African American communities. Our work aimed to describe the inequities in increased rates of pelvic inflammatory disease and tubal factor infertility as it relates to African American women. In addition, we highlighted the need for improved access to screening and treatment of sexually transmitted infections, access to barrier contraception, and health literacy related to the understanding and prevention of tubal factor infertility in African American women.

Massive ovarian edema masquerading as an androgen-secreting tumor.

OBJECTIVE: To highlight the management of massive ovarian edema in young reproductive-age women. DESIGN: A case report of a healthy female with clitoromegaly and elevated androgen levels secondary to massive ovarian edema. SETTING: Reproductive Endocrinology and Infertility Department of an academic hospital. PATIENT: A healthy 20-year-old woman who presented for routine gynecological care and was found to have a 2-cm clitoromegaly and elevated androgen levels. INTERVENTIONS: The patient underwent a diagnostic laparoscopy and right oophorectomy. MAIN OUTCOME MEASURES: Measurement of androgen levels. RESULTS: Final pathology showed massive edema of the ovary with no evidence of malignancy or androgen-secreting tumor cells. In addition, resolution of the elevated androgen levels was observed. CONCLUSIONS: Massive ovarian edema due to asymptomatic subacute torsion should be included in the differential diagnosis of reproductive-age patients who present with ovarian mass and hyperandrogenemia within the tumor range. Although not performed in our case, conservative management that involves detorsion, ovarian biopsy, and oophoropexy to prevent a recurrence should be the treatment of choice.

Pulmonary metastasis as a primary manifestation of gestational choriocarcinoma in a third trimester pregnancy.

•Choriocarcinomas can follow molar, ectopic, or normal pregnancies.•The early diagnosis and treatment of choriocarcinomas is imperative.•Atypical symptoms in pregnancy should raise suspicion for choriocarcinoma.•Choriocarcinoma must always be in the differential in uncomplicated term pregnancies.

Hysteroscopic Morcellation in Endometrial Cancer Diagnosis: Increased Risk?

STUDY OBJECTIVE: Operative hysteroscopy requires elevated intrauterine pressures, which could lead to the spread of malignant cells into the peritoneal cavity. Currently, there is a paucity of data analyzing clinical outcomes in endometrial cancer after hysteroscopic morcellation with newer equipment. In this study, we sought to determine whether there are increased rates of positive peritoneal cytology, lymphovascular space invasion, or surgical upstaging in patients undergoing hysteroscopic morcellation compared with alternative endometrial biopsy methods. DESIGN: A retrospective chart review of patients from 2013-2018 was performed. The exclusion criteria included biopsy at outside institution, stage IV endometrial cancer known before biopsy, and missing data regarding biopsy method and histology. Peritoneal cytology results, lymphovascular space invasion, and surgical staging were compared by method of biopsy and histology using chi-square and Kruskal-Wallis tests. SETTING: The patients included in this study were accrued from the Karmanos Cancer Insittute in Detroit, Michigan. PATIENTS: A total of 289 patients met the inclusion criteria: 184 patients were classified as low-grade (Fédération Internationale de Gynécologie et d'Obstétrique grades 1 and 2) and 105 as high-grade (Fédération Internationale de Gynécologie et d'Obstétrique grade 3, serous, clear cell, and carcinosarcoma) endometrial cancer. INTERVENTIONS: Fifty-three patients (18%) underwent hysteroscopy with morcellation. Alternative biopsy methods included hysteroscopy without morcellation, n = 81 (28%); endometrial biopsy, n = 112 (38.7%); and dilation and curettage, n = 43 (15%). MEASUREMENTS AND MAIN RESULTS: Positive peritoneal cytology was noted in 34 cases (12%) and negative cytology in 165 (57%). Cytology was not performed in 90 cases (31%). When comparing outcomes by histologic subtypes, no difference was seen in peritoneal cytology (p = .704 and .727 for low grade and high grade, respectively), stage (p = .773 and .053 for low grade and high grade, respectively) or lymphovascular space invasion (p = .400 and .142 for low grade and high grade, respectively). CONCLUSION: Our study demonstrates that hysteroscopy with morcellation is a safe diagnostic method for low- and high-grade endometrial pathologic conditions and does not lead to increased dissemination of malignant cells, lymphovascular space invasion, or upstaging of patients.

Programmed Death Ligand 1 Expression Among 700 Consecutive Endometrial Cancers: Strong Association With Mismatch Repair Protein Deficiency.

OBJECTIVE: This study aims to determine the prevalence of programmed death ligand 1 (PD-L1) expression in endometrial carcinoma (EC) and determine clinical and pathological associations. METHODS: Immunohistochemistry for PD-L1 was performed on sections of a triple-core tissue microarray of 700 ECs. Positive PD-L1 expression, defined as 1% of cells staining positive, was evaluated in tumor and stromal compartments. Using age-adjusted logistic regression, we estimated odds ratios and 95% confidence intervals for associations between PD-L1 expression (overall and by staining compartment) with clinical and tumor characteristics. Kaplan-Meier plots and log-rank tests were used to evaluate associations between PD-L1 expression and EC-specific survival. RESULTS: PD-L1 expression was observed in 100 cases (14.3%), including 27 (3.9%) with expression in tumor cells only, 35 (5.0%) with expression in both tumor cells and stroma, and 38 (5.4%) with expression in stroma only. Expression was observed in ECs of different histologic types. Tumors characterized by loss of mismatch repair proteins were significantly associated with tumoral PD-L1 expression (P < 0.0001), but not with stromal PD-L1 expression. Both tumoral and stromal PD-L1 expressions were associated with high-grade endometrioid histology, nonendometrioid histology, and lymphovascular space invasion. We observed no significant associations between PD-L1 expression and EC-specific survival. CONCLUSIONS: PD-L1 is expressed in a significant proportion of EC and is associated with mismatch repair deficiency, potentially representing a mechanism of tumor immune evasion and a therapeutic target in EC.