Gynecological malignancies and obesity.

The global pandemic of obesity has had a significant impact on gynecological malignancies, most notably endometrial cancer. It has resulted in worldwide increases in the incidence of endometrial cancer and a change in patient demographics, resulting in more diagnoses than ever before being made in pre-menopausal women, who are often keen to pursue fertility-sparing treatments. Obesity increases the risk of gynecological cancers by creating a pro-carcinogenic environment of unopposed estrogen, hyperinsulinemia, and chronic inflammation. It can present both a diagnostic challenge and strongly influence management decisions, including the practicalities of performing surgery, increase anesthetic risks, and alter response rates to adjuvant and medical therapies. Obesity may also influence endometrial cancer mortality and certainly contributes to poorer overall survival due to an excess of deaths related to cardiovascular disease. Weight loss may well, therefore, be the key to the prevention of gynecological cancers and their recurrence.

Serum HE4 predicts progestin treatment response in endometrial cancer and atypical hyperplasia: A prognostic study.

OBJECTIVE: To investigate serum human epididymis-4 (HE4) as a predictive biomarker of intrauterine progestin response in endometrial cancer and atypical endometrial hyperplasia (AEH). DESIGN: Prospective prognostic factor study. SETTING: Consecutive sample of women attending a tertiary gynaecological oncology centre in northwest England. POPULATION: Women with AEH or early-stage, low-grade endometrial cancer who were unfit for or declined primary surgical management. METHODS: A total of 76 women, 32 with AEH and 44 with endometrial cancer, were treated with a levonorgestrel intrauterine system (LNG-IUS) for 12 months. Endometrial biopsies and imaging were performed to assess treatment response. Pretreatment serum HE4 was analysed by chemiluminescence immunoassay and diagnostic accuracy and logistic regression analyses were performed. MAIN OUTCOME MEASURES: Progestin response at 12 months defined by histology and imaging. RESULTS: The median age and body mass index (BMI) of the final cohort were 52 years (interquartile range [IQR] 33-62 years) and 46 kg/m2 (IQR 38-54 kg/m2 ), respectively. Baseline serum HE4 was significantly higher in non-responders than responders (119.2 pmol/L, IQR 94.0-208.4 pmol/L versus 71.8 pmol/L, IQR 56.1-84.2 pmol/L, p < 0.001). Older age (odds ratio [OR] 0.96, 95% CI 0.93-0.99, p = 0.02), baseline serum HE4 (OR 0.97, 95% CI 0.96-0.99, p = 0.001) and endometrial cancer histology (OR 0.22, 95% CI 0.72-0.68, p = 0.009) were associated with a lower likelihood of progestin treatment response. Serum HE4 remained independently associated with progestin treatment failure when adjusted for age and histology (adjusted hazard ratio 0.97, 95% CI 0.96-0.99, p = 0.008). CONCLUSION: Serum HE4 shows promise as a predictive biomarker of progestin treatment response in endometrial cancer and AEH.

Impact of Type 2 Diabetes Mellitus on Endometrial Cancer Survival: A Prospective Database Analysis.

Purpose: Type 2 diabetes mellitus (T2DM) is an established risk factor for endometrial cancer but its impact on endometrial cancer survival outcomes is unclear. The aim of this study was to investigate whether pre-existing T2DM impacts survival outcomes in endometrial cancer. Patients and Methods: Women diagnosed with endometrial cancer were recruited to a single centre prospective cohort study. Relevant sociodemographic and clinico-pathological data were recorded at baseline. T2DM status was based on clinical and biochemical assessment, verified by general practitioner records and analysed in relation to overall, cancer-specific and recurrence-free survival using Kaplan-Meier estimation and multivariable Cox-regression. Results: In total, 533 women with median age and BMI of 66 years (Interquartile range (IQR), 56, 73) and 32kg/m2 (IQR 26, 39) respectively, were included in the analysis. The majority had low-grade (67.3%), early-stage (85.1% stage I/II), endometrial cancer of endometrioid histological phenotype (74.7%). A total of 107 (20.1%) had pre-existing T2DM. Women with T2DM had a two-fold increase in overall mortality (adjusted HR 2.07, 95%CI 1.21-3.55, p=0.008), cancer-specific mortality (adjusted HR 2.15, 95% CI 1.05-4.39, p=0.035) and recurrence rates (adjusted HR 2.22, 95% CI 1.08-4.56, p=0.030), compared to those without, in multivariable analyses. Conclusion: T2DM confers an increased risk of death in endometrial cancer patients. Well-designed longitudinal studies with large sample sizes are now needed to confirm these findings.