Trends in incidence and hormonal management of endometrial cancer during potentially reproductive age in Japan: a population-based study.

BACKGROUND: We aimed to investigate the trends in the incidence and treatment of endometrial cancer (EC) during potentially reproductive age in Japan, with a special focus on the relative oncologic safety of hormonal therapy (HT) over surgery. METHODS: This population-based retrospective cohort study was conducted using data from the Osaka Cancer Registry from 2004 to 2018. Women with EC were first identified and then distributions of age, stage, histology, and initial treatment were examined. Then, the relative oncologic safety of HT over surgery in patients under the age of 50 years was evaluated. RESULTS: Among the 9417 patients with EC, 1937 were diagnosed during their potentially reproductive age (< 50 years). The incidence of EC during potentially reproductive age has increased from 18.5% in 2004-2011 to 21.9% in 2012-2018. ECs during potentially reproductive age more frequently displayed favorable characteristics, such as endometrioid histology, and lower histological grade than those in non-potentially reproductive age. Among the 1223 patients diagnosed with localized endometrioid EC, 74 cases (6.0%) received HT as an initial treatment, while 1100 cases (90.0%) underwent surgery as their initial treatment. When the two treatment groups were compared, there was no significant difference in overall survival (p = 0.3713). The estimated 5-year survival rates were 100 and 98.8% in the HT and surgery groups, respectively. CONCLUSION: EC is increasingly diagnosed during potentially reproductive age in Japan. The use of HT as an initial treatment is increasing, and achieved comparable survival outcomes to urgery against localized endometrioid EC during the potentially reproductive age.

Real-world prevalence of microsatellite instability testing and related status in women with advanced endometrial cancer in Europe.

PURPOSE: To assess the real-world prevalence of microsatellite instability (MSI)/mismatch repair (MMR) testing and related tumor status in recurrent/advanced endometrial cancer patients in Europe. METHODS: Data were from two multi-center, retrospective patient chart review studies conducted in the United Kingdom, Germany, Italy, France and Spain: The Endometrial Cancer Health Outcomes-Europe-First-Line (ECHO-EU-1L) study and the ECHO-EU-Second-Line (ECHO-EU-2L) study. ECHO-EU-1L included recurrent/advanced endometrial cancer patients who received first-line systemic therapy between 1/JUN/2016 and 31/MAR/2020 after recurrent/advanced diagnosis. ECHO-EU-2L included patients with recurrent/advanced endometrial cancer who progressed between 1/JUN/2016 and 30/JUN/2019 following prior first-line systemic therapy. Data collected included patient demographics, MSI/MMR tumor testing and results, and clinical/treatment characteristics. RESULTS: ECHO-EU-1L included 242 first-line patients and ECHO-EU-2L included 475 s-line patients. For all patients, median age at recurrent/advanced diagnosis was 69 years, roughly half had endometrioid carcinoma histology and over 75% had Stage IIIB-IV disease at initial diagnosis. The prevalence of MSI/MMR testing in the first-line and second-line cohorts was similar (36.4 and 34.9%, respectively). Among those tested, a majority had non-MSI-high/MMR proficient tumors (80.7 and 74.7% among first- and second-line patients, respectively). About 15% had MSI-high/MMR deficient tumors in both cohorts, and a few patients had discordant results (3.4 and 10.8% among first- and second-line patients, respectively). CONCLUSION: Prior to the approvals of biomarker-directed therapies for recurrent/advanced endometrial cancer patients in Europe, there were low MSI/MMR testing rates for these patients of just over one-third. Given the availability of biomarker-directed therapies, increased MSI/MMR testing may help inform treatment decisions for recurrent/advanced endometrial cancer patients in Europe.

An analysis of clinical characteristics and prognosis of endometrioid ovarian cancer based on the SEER database and two centers in China.

PURPOSE: To assess the clinical characteristics and the risk factors related to the unfavorable prognosis of endometrioid ovarian carcinoma (EOVC) based on data from the Surveillance, Epidemiology, and End Results (SEER) database and two clinical centers in China. METHODS: Data were extracted from the SEER database and two clinical centers in China (2010 ~ 2021), 884 cases and 87 patients with EOVC were selected, respectively. Overall survival (OS) and progression-free survival (PFS) were compared among the different groups using Kaplan-Meier analysis. The Cox proportional-hazards model was used to identify independent prognostic factors related to EOVC. A nomogram was constructed based on the risk factors of the SEER database affecting prognosis and the discrimination and calibration of the nomogram were evaluated by C-index and calibration curves. RESULTS: The average age at diagnosis of patients with EOVC in the SEER database and two centers in China was 55.77 ± 12.40 years and 47.14 ± 11.50 years, 84.7% and 66.6% of them were diagnosed at FIGO stage I ~ II, respectively. In the SEER database, age over 70 years, advanced FIGO stage, tumor grade 3, only unilateral salpingo-oophorectomy were independent risk factors of unfavorable prognosis. In two clinical centers in China, 27.6% of EOVC patients were diagnosed with synchronous endometriosis. Advanced FIGO stage, HE4 > 179 pmol/L and bilateral ovarian involvement significantly correlated with poor OS and PFS in Kaplan-Meier analysis. Body mass index (BMI) < 19.34 kg/m2 was an independent risk factor relating to OS and PFS. Additionally, C-index of internal and external verification for the nomogram were 0.812 and 0.754 respectively, revealing good accuracy and clinical applicability. CONCLUSIONS: Most patients were diagnosed at early stage, low grade and had better prognosis. Asian/Pacific Islander and Chinese diagnosed with EOVC were more likely to be younger than whites and blacks. Age, tumor grade and FIGO stage (SEER database) and BMI (two centers) are independent prognostic factors. HE4 appears to be more valuable in prognostic assessment compared with CA125. The nomogram had good discrimination and calibration for predicting prognosis, providing a convenient and reliable tool for clinical decision-making for patients with EOVC.

Endometrial cancer with concomitant endometriosis is highly associated with ovarian endometrioid carcinoma: a retrospective cohort study.

BACKGROUND: Endometriosis is assumed to be involved in ovarian cancer development, which is called endometriosis-associated ovarian cancer (EAOC). Uterine endometrial cells may be the cell of origin of EAOC. Accumulated carcinogenic changes in the uterine endometrial cells may increase the risk of developing EAOC. To further understand the pathogenesis of EAOCs, we focused on the clinicopathological characteristics of EAOCs in endometrial cancer patients with concomitant endometriosis. METHODS: We retrospectively reviewed 376 patients who were surgically treated for stage I-III endometrial cancer. Clinicopathological characteristics were compared between patients with and without endometriosis. Furthermore, the incidence of simultaneous endometrial and ovarian cancer (SEOC) and the histological characteristics of SEOC were compared between the two groups. RESULTS: Among 376 patients with endometrial cancer, 51 had concomitant endometriosis. Patients with endometriosis were significantly younger and more frequently had endometrioid G1/G2 tumors than those without endometriosis. The incidence of SEOCs was significantly higher in endometrial cancer patients with endometriosis than those without it (p < 0.0001); notably, 12 of 51 endometrial cancer patients with endometriosis (24%) had SEOCs. All of the ovarian cancers in endometrial cancer patients with endometriosis were endometrioid carcinomas. Moreover, even in those without endometriosis, endometrioid carcinoma was the most common histological type of SEOC. CONCLUSION: We revealed that endometrial cancer patients with endometriosis had a high probability of SEOC and that endometrioid carcinoma was the most common histological subtype of SEOC regardless of the presence of endometriosis. For patients with endometrial cancer and endometriosis, careful examination of ovarian endometriotic lesions may be important to detect EAOCs.

Incidence and survival of epithelial ovarian, fallopian tube, peritoneal, and undesignated abdominal/pelvic cancers in Sweden 1960-2014: A population-based cohort study.

BACKGROUND: Despite improved surgical and oncological treatment, ovarian cancer continues to be the most lethal of the gynecologic malignancies. We aimed to analyze survival trends in epithelial ovarian cancer with regard to age, tumor site, and morphology in Sweden 1960 to 2014. METHODS: A nationwide population-based study was conducted using data from the Swedish Cancer Registry on 46,350 women aged 18 or older with a diagnosis of epithelial ovarian, fallopian tube, peritoneal, or undesignated abdominal/pelvic cancer 1960 to 2014. Analyses of age-standardized incidence and relative survival (RS) were performed and time trends modelled according to age, tumor site, and morphology. RESULTS: Overall incidence of ovarian, tubal, peritoneal, and undesignated abdominal/pelvic cancers declined since 1980. Median age at diagnosis increased. Serous carcinoma increased in incidence. RS at 1, 2 and 5 years from diagnosis improved since 1960, although not for the youngest and the oldest patients. Ten-year RS did not improve. The best RS was found for fallopian tube cancer and the worst RS for undesignated abdominal/pelvic cancer. Among the morphologic subgroups, endometrioid carcinoma had the best RS. CONCLUSIONS: Survival in epithelial ovarian, tubal, peritoneal, and undesignated abdominal/pelvic cancers in Sweden has improved over the last six decades. Advances in epithelial ovarian cancer treatment have extended life for the first 5 years from diagnosis but 10-year survival remains poor.

Stratified follow-up for endometrial cancer: a move to more personalized cancer care.

OBJECTIVE: Hospital based follow-up has been the standard of care for endometrial cancer. Patient initiated follow-up is a useful adjunct for lower risk cancers. The purpose of this study was to evaluate outcomes of endometrial cancer patients after stratification into risk groupings, with particular attention to salvageable relapses. METHODS: All patients treated surgically for International Federation of Gynecology and Obstetrics (FIGO) stage I-IVA endometrial cancer of all histological subtypes, from January 2009 until March 2019, were analyzed. Patient and tumor characteristics, treatment details, relapse, death, and last follow-up dates were collected. Site of relapse, presence of symptoms, and whether relapses were salvageable were also identified. The European Society of Medical Oncology-European Society of Gynecological Oncology 2020 risk stratification was assigned, and relapse free and overall survival were estimated. RESULTS: 900 patients met the eligibility criteria. Median age was 66 years (range 28-96) and follow-up duration was 35 months (interquartile range 19-57). In total, 16% (n=144) of patients relapsed, 1.3% (n=12) from the low risk group, 3.9% (n=35) from the intermediate risk group, 2.2% (n=20) from the high-intermediate risk group, and 8.7% (n=77) from the high risk group. Salvageable relapses were less frequent at 2% (n=18), of which 33% (n=6) were from the low risk group, 22% (n=4) from the intermediate risk group, 11% (n=2) from the high-intermediate risk group, and 33% (n=6) from the high risk group. There were only three asymptomatic relapses in the low risk patients, accounting for 0.33% of the entire cohort. CONCLUSIONS: Relapses were infrequent and most presented with symptoms; prognosis after relapse remains favorable. Overall salvageable relapses were infrequent and cannot justify intensive hospital based follow-up. Use of patient initiated follow-up is therefore appropriate, as per the British Gynaecological Cancer Society's guidelines, for all risk groupings.

A single centre experience of metabolic syndrome and endometrial carcinoma: 5 years review.

Endometrial cancer (EC) has been found to have a strong association with overweight and obesity. The aim of this study was to evaluate the link between metabolic syndrome and EC among patients. A total of 119 patients with histologically confirmed EC were recruited. About 102 cases of endometrioid carcinoma (Type I) and serous (n = 7), clear cell (n = 3) and carcinosarcoma (n = 7) were the Type II. Metabolic syndrome was significantly associated with increased risk of Type I EC (OR = 3.43, 95% CI = 1.12-10.46, p < .05) where obesity risk revealed as the main factor in Type I EC (OR = 3.88, 95% CI = 1.27-11.85, p < .05). There was no significant difference between both subtypes with other metabolic components and no impact on patients' overall survival and disease-free survival (p > .05). Metabolic syndrome was positively associated with an increased risk of Type I EC with obesity being the most influential risk factor.Impact statementWhat already known on this subject? Endometrial cancer (EC) is one of the most prevalent cancers worldwide and have a strong association with overweight and obesity of at least 40%, but there is conflicting evidence of an association of EC with metabolic syndrome (MS).What result of this study add? This study evaluated the link between EC and MS, such as high blood pressure, BMI, fasting blood sugar, triglyceride, Hyper Density Lipoprotein (HDL).What implications are of these findings for clinical practice & further research? Type I EC had and association with MS with obesity is the most potent risk factor. As the prevalence of metabolic syndrome is alarmingly high among adult Malaysians, the incidence of EC is projected to increase in the coming years. Proactive preventative measures and intervention essential for reducing the incidence of endometrial cancers. Future research to clarify the association between metabolic syndrome and endometrial cancer survival and to investigate other lifestyle factors that may affect the prognosis is needed.

Perioperative outcomes of women with and without class III obesity undergoing hysterectomy for endometrioid endometrial cancer: A population-based study.

OBJECTIVE: Population-based data on perioperative complications among women with endometrial cancer and severe obesity are lacking. We evaluated 30-day complication rates among women with and without class III obesity (body mass index ≥ 40 kg/m2) undergoing primary surgical management for endometrioid endometrial cancer (EEC), and how outcomes differed according to surgical approach (open vs. minimally invasive). METHODS: We performed a retrospective population-based cohort study of women with EEC undergoing hysterectomy in Ontario, Canada, between 2006 and 2015. We evaluated perioperative complications in the whole cohort, and in a 1:1 matched analysis using hard and propensity score matching to ensure similar distributions of patient, tumour, provider and institution-level factors between women with and without class III obesity (identified using a surgical billing code). The primary outcome of interest was the 30-day perioperative complication rate. RESULTS: 12,112 women met inclusion criteria; 2697 (22.3%) had class III obesity. We matched 2320 (86%) women with class III obesity to those without. The composite complication rate was significantly higher among women with class III obesity (23.2% vs. 18.4%, standardized mean difference [SMD] = 0.12), primarily due to wound infection/disruption (12.1% vs. 6.2%). There was no difference in outcomes for women with and without class III obesity when a minimally invasive approach was used. CONCLUSIONS: Wound infection/disruption was increased for women with class III obesity compared to women without. Otherwise, perioperative complications were similar between the matched pairs. When minimally invasive approaches were used, women with class III obesity had a similar risk of complications as women without obesity.

Lymph node metastasis probability in young patients eligible for conservative management of endometrial cancer.

OBJECTIVE: Endometrial cancer (EC) is a rare condition in young women. The objective of this study was to evaluate the risk of pelvic lymph node (LN) metastasis in young women with EC who are candidates for conservative management. METHODS: Using the SEER database, a population-based analysis was conducted to identify women <45 years with grade 1, 2, or 3 endometrioid adenocarcinoma stage IA (FIGO 2009) who underwent pelvic lymphadenectomy with at least ten LNs removed. The LN macrometastases rate based on conventional histological diagnosis was analyzed according to tumor grade and myometrial invasion (MI) on final histology. RESULTS: A cohort of 1284 women was analyzed. The LN metastasis rates were: 2/414 (0.5%) grade 1 EC without MI, 5/239 (2.1%) grade 2 or 3 EC without MI, 5/308 (1.6%) grade 1 EC with MI, and 14/323 (4.3%) grade 2 or 3 EC with MI. Tumor size was not correlated with LN metastasis probability. CONCLUSIONS: Young patients eligible for conservative management have a low rate of LN macrometastasis, especially in stage IA without MI grade 1 EC. A systematic lymphadenectomy should not be performed in these patients. Prospective study evaluating the sentinel LN mapping in conservative management of EC could be performed to assess the LN micrometastasis rate.

A modern assessment of the surgical pathologic spread and nodal dissemination of endometrial cancer.

OBJECTIVE: To examine the risk of nodal metastases in a contemporary cohort of women based on pathologic risk factors including histology, depth of invasion, tumor grade, and lymphovascular space invasion. METHODS: Women with endometrial cancer who underwent hysterectomy from 2004 to 2016 who were registered in the National Cancer Database were analyzed. Patients were stratified by T stage: T1A (<50% myometrial invasion), T1B (>50% myometrial invasion) and T2 (cervical involvement). Lymph node metastases were assessed in relation to tumor T stage and grade, and further stratified by lymphovascular space invasion. RESULTS: We identified 161,960 patients. The rate of nodal metastases within the endometrioid histology cohort was 2.2% for T1A cancers, 12.8% for T1B cancers and 19.9% for T2 cancers. For stage TIA cancers, the percent of patients with positive nodes increased from 1.1% for grade 1 cancers, to 2.9% for grade 2 cancers to 4.8% for grade 3 cancers. The corresponding rates of nodal metastases for stage T1B cancers were 8.6%, 13.7%, and 16.9%, respectively. For T1A cancers without lymphovascular space invasion, nodal metastases ranged from 0.6% in those with grade 1 cancers to 3.0% for grade 3 cancers. The corresponding risk of nodal disease ranged from 11.8% to 13.9% for T1A cancers with lymphovascular space invasion. CONCLUSIONS: There was a sequential increase in the risk of lymph node metastases based on depth of uterine invasion, tumor grade, and the presence of lymphovascular space invasion. The overall rate of nodal metastasis is lower than reported in the original GOG 33.

Incidence of endometrioid and clear-cell ovarian cancer in histological proven endometriosis: the ENOCA population-based cohort study.

BACKGROUND: Several studies have suggested that endometriosis is associated with an increased risk of ovarian cancer, especially for the clear-cell and endometrioid subtypes. However, previous studies lack sufficient power or diagnostic certainty. OBJECTIVE: The objective of the study was to assess the association between histologically proven endometriosis and ovarian cancer in a large population-based cohort study. STUDY DESIGN: We identified 131,450 women with a histological diagnosis of endometriosis between 1990 and 2015 from the Dutch nationwide registry of histopathology and cytopathology (PALGA). For the control cohort 132,654 women with a benign dermal nevus were matched on age and inclusion year with the endometriosis cases. Histological diagnoses of ovarian, fallopian tubes, and peritoneal cancers between January 1990 and July 2017 were retrieved. Incidence rate ratios were estimated for ovarian cancer and its subtypes for the whole follow-up period as well as for women with more than 1 person-year at risk. RESULTS: We found a crude incidence rate ratio of 4.79 (95% confidence interval, 4.33-5.31) and an age-adjusted incidence rate ratio of 7.18 (95% confidence interval, 6.17-8.36) for ovarian cancer overall. Endometrioid and clear-cell ovarian cancer had the highest age-adjusted incidence rate ratio of 29.06 (95% confidence interval, 20.66-40.87) and 21.34 (95% confidence interval, 14.01-32.51), respectively. Median age at ovarian cancer diagnosis was 56 years (interquartile range, 49-63) for the endometriosis cohort and 60 years (interquartile range, 53-67) for the nevus cohort, (P < .05). After excluding women with less than 1 person-year at risk following an endometriosis diagnosis, we found a crude incidence rate ratio of 1.04 (95% confidence interval, 0.91-1.19) and an age-adjusted incidence rate ratio of 1.08 (95% confidence interval, 0.87-1.35) for ovarian cancer overall. However, statistically significant age-adjusted incidence rate ratios of 2.29 (95% confidence interval, 1.24-4.20) for clear-cell ovarian cancer and 2.56 (95% confidence interval, 1.47-4.47) for endometrioid ovarian cancer were found. CONCLUSION: A significantly higher incidence of clear-cell and endometrioid ovarian cancer was found in women with histologically proven endometriosis. Additionally, we found an increased incidence of all ovarian cancer subtypes in histologically proven endometriosis; however, in many of these women, endometriosis and ovarian cancer were diagnosed synchronously after the average menopausal age, which may suggest that the risk of ovarian cancer in endometriosis patients remains, even when clinical endometriosis symptoms are no longer present.

Preoperative predictors of endometrial cancer at time of hysterectomy for endometrial intraepithelial neoplasia or complex atypical hyperplasia.

BACKGROUND: Endometrial intraepithelial neoplasia, also known as complex atypical hyperplasia, is a precancerous lesion of the endometrium associated with a 40% risk of concurrent endometrial cancer at the time of hysterectomy. Although a majority of endometrial cancers diagnosed at the time of hysterectomy for endometrial intraepithelial neoplasia are low risk and low stage, approximately 10% of patients ultimately diagnosed with endometrial cancers will have high-risk disease that would warrant lymph node assessment to guide adjuvant therapy decisions. Given these risks, some physicians choose to refer patients to a gynecologic oncologist for definitive management. Currently, few data exist regarding preoperative factors that can predict the presence of concurrent endometrial cancer in patients with endometrial intraepithelial neoplasia. Identification of these factors may assist in the preoperative triaging of patients to general gynecology or gynecologic oncology. OBJECTIVE: To determine whether preoperative factors can predict the presence of concurrent endometrial cancer at the time of hysterectomy in patients with endometrial intraepithelial neoplasia; and to describe the ability of preoperative characteristics to predict which patients may be at a higher risk for lymph node involvement requiring lymph node assessment at the time of hysterectomy. MATERIALS AND METHODS: We conducted a retrospective cohort study of women undergoing hysterectomy for pathologically confirmed endometrial intraepithelial neoplasia from January 2004 to December 2015. Patient demographics, imaging, pathology, and outcomes were recorded. The "Mayo criteria" were used to determine patients requiring lymphadenectomy. Unadjusted associations between covariates and progression to endometrial cancer were estimated by 2-sample t-tests for continuous covariates and by logistic regression for categorical covariates. A multivariable model for endometrial cancer at the time of hysterectomy was developed using logistic regression with 5-fold cross-validation. RESULTS: Of the 1055 charts reviewed, 169 patients were eligible and included. Of these patients, 87 (51.5%) had a final diagnosis of endometrial intraepithelial neoplasia/other benign disease, whereas 82 (48.5%) were ultimately diagnosed with endometrial cancer. No medical comorbidities were found to be strongly associated with concurrent endometrial cancer. Patients with endometrial cancer had a thicker average endometrial stripe compared to the patients with no endometrial cancer at the time of hysterectomy (15.7 mm; standard deviation, 9.5) versus 12.5 mm; standard deviation, 6.4; P = .01). An endometrial stripe of ≥2 cm was associated with 4.0 times the odds of concurrent endometrial cancer (95% confidence interval, 1.5-10.0), controlling for age. In all, 87% of endometrial cancer cases were stage T1a (Nx or N0). Approximately 44% of patients diagnosed with endometrial cancer and an endometrial stripe of ≥2 cm met the "Mayo criteria" for indicated lymphadenectomy compared to 22% of endometrial cancer patients with an endometrial stripe of <2 cm. CONCLUSION: Endometrial stripe thickness and age were the strongest predictors of concurrent endometrial cancer at time of hysterectomy for endometrial intraepithelial neoplasia. Referral to a gynecologic oncologist may be especially warranted in endometrial intraepithelial neoplasia patients with an endometrial stripe of ≥2 cm given the increased rate of concurrent cancer and potential need for lymph node assessment.

Clinical patterns and genomic profiling of recurrent 'ultra-low risk' endometrial cancer.

OBJECTIVE: Despite good prognosis for patients with low-risk endometrial cancer, a small subset of women with low-grade/low-stage endometrial cancer experience disease recurrence and death. The aim of this study was to characterize clinical features and mutational profiles of recurrent, low-grade, non-myoinvasive, 'ultra-low risk' endometrioid endometrial adenocarcinomas. METHODS: We retrospectively identified patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA endometrioid endometrial cancers who underwent primary surgery at our institution, between January 2009 and February 2017, with follow-up of ≥12 months. 'Ultra-low risk' was defined as FIGO tumor grade 1, non-myoinvasive, and lacking lymphovascular space invasion. Tumor-normal profiling using massively parallel sequencing targeting 468 genes was performed. Microsatellite instability was assessed using MSIsensor. DNA mismatch repair (MMR) protein proficiency was determined by immunohistochemistry. RESULTS: A total of 486 patients with ultra-low risk endometrioid endometrial cancers were identified: 14 (2.9%) of 486 patients developed a recurrence. Median follow-up for non-recurrent endometrioid endometrial cancers: 34 (range 12-116) months; for recurrent endometrioid endometrial cancers: 50.5 (range 20-116) months. Patients with recurrent disease were older, had lower body mass index, and were most commonly non-White (p=0.025, p<0.001, and p<0.001, respectively). Other clinical characteristics did not differ. MMR immunohistochemistry was obtained for 211 (43%) tumors: 158 (75%) MMR-proficient and 53 (25%) MMR-deficient. Primary tumors of 9 recurrent and 27 non-recurrent endometrioid endometrial cancers underwent mutational profiling. Most were microsatellite stable (6/9, 67% recurrent; 25/27, 93% non-recurrent). Recurrent PTEN and PIK3CA mutations were present in both groups. Exon 3 CTNNB1 hotspot mutations were found in 4/9 (44%) recurrent and 8/27 (30%) non-recurrent (p=0.44). CONCLUSIONS: Patients diagnosed with ultra-low risk endometrioid endometrial cancers have an overall excellent prognosis. However, in our study, 2.9% of patients with no identifiable clinical or pathologic risk factors developed recurrence. Further work is warranted to elucidate the mechanism for recurrence in this population.

Serum HSP70 level in patients with endometrial cancer with and without diabetes.

Diabetes mellitus (DM) is associated with an increased risk of endometrial carcinoma (EC). Heat shock proteins have a role in the modulation of both diseases. The aim of this study was to investigate extracellular HSP70 (eHSP70) level alternations in patients with two different types of EC (endometrioid and non-endometrioid) with and without type 2 diabetes. In a case-control study, 88 participants were enrolled in four groups including: 18 EC patients with DM, 19 EC patients without DM, 29 patients with DM, and 22 healthy individuals. Blood samples were taken before surgery in cancer patients. Estradiol, eHSP70, sex hormone-binding globulin (SHBG), FBS, and HbA1c were assessed. Serum HSP70 level was higher in patients with diabetes (52.24 ± 14.2 ng/ml) compared to healthy controls (39.04 ± 6.96) (p < .05). It was lower in EC (26.05 ± 12.28) compared to healthy controls (39.04 ± 6.96) (p < .05). eHSP70 was also lower in endometrioid-type carcinoma (22.57 ± 11) compared to non-endometrioid type (31.55 ± 12.38) (p < .05). Further analysis showed increased levels of eHSP70 in patients having both endometrioid-type carcinoma and diabetes (27.23 ± 11.41) compared to the same patients without DM (17.08 ± 7.78) (p < .05). Presence of diabetes in patients with endometrioid type carcinoma resulted in an increase in eHSP70 approaching the level of eHSP70 in patients with non-endometrioid histology.

Minimally Invasive Surgery Rate as a Quality Metric for Endometrial Cancer.

STUDY OBJECTIVE: To determine the frequency with which Commission on Cancer-accredited hospitals met a metric of ≥80% minimally invasively performed hysterectomies for endometrial cancer and to compare the clinical outcomes of hospitals meeting this metric with those that did not. DESIGN: Retrospective cohort study. SETTING: Hospitals caring for ≥20 endometrial cancer patients per year recorded in the National Cancer Database in 2015 were included. PATIENTS: Women who had undergone hysterectomy for endometrial cancer and had an epithelial histology, a Charlson comorbidity score of 0, and stage I to III disease. INTERVENTION: Patient characteristics, patterns of care, and outcomes were compared between hospitals performing ≥80% minimally invasive hysterectomies and hospitals not meeting this metric. MEASUREMENTS AND MAIN RESULTS: The hospitals (n = 510) treated 20 670 women with endometrial cancer. In 283 (55%) hospitals ≥80% of hysterectomies were minimally invasively performed (high-minimally invasive surgery [MIS] hospitals, overall MIS rate 89%). In the 227 hospitals that did not meet this metric, 61% of hysterectomies for endometrial cancer were performed using a minimally invasive approach. In high-MIS hospitals, patients were more likely to be white (87% vs 82%, p<.001), privately insured (53% vs 49%, p <.001), and have stage I disease (84% vs 82%, p = .002) and an endometrioid histology (79% vs 76%, p <.001). Surgery was more often performed robotically (80% vs 71%), and conversion to laparotomy was less likely (1.5% vs 3.2%, adjusted odds ratio [aOR], 0.47; 95% confidence interval [CI], 0.39-0.57) (both p <.001). Patients treated at high-MIS hospitals were more likely to have undergone lymph node assessment at the time of surgery (76% vs 69%; aOR, 1.43; 95% CI, 1.35-1.53) and been discharged on the same or next day (74% vs 57%; aOR, 2.27; 95% CI, 2.13-2.42) and were less likely to have an unplanned 30-day readmission (1.8% vs 2.9%; aOR, 0.64; 95% CI, 0.53-0.77). CONCLUSION: An MIS rate of ≥80% for endometrial cancer is feasible on a national scale and is associated with other hospital-level measurements of high-quality care.

Perineal Talc Use, Douching, and the Risk of Uterine Cancer.

BACKGROUND: Perineal talc use and douching could affect the risk of uterine cancer through several possible pathways, including inflammation response, microbiota changes, or endocrine disruption. Two previous cohort studies of the association between talc use and uterine cancer have reported weak positive associations, but we know of no previous evaluations of the relationship between douching and uterine cancer. METHODS: Using a large prospective cohort, we examined the relationship between incident uterine cancer and self-reported use of talc or douche using Cox proportional hazards models. RESULTS: After excluding those with prior hysterectomy, 271 of 33,609 women reported incident uterine cancer (mean follow-up = 8.3 years in noncases; maximum 12.6 years). Overall, 26% of women reported ever using talc and 15% reported ever having douched. Ever talc use was associated with an increase in risk of uterine cancer (adjusted hazard ratio [HR] = 1.2; 95% confidence interval [CI] = 0.94, 1.6), with some evidence of a dose-response for frequency of talc use (P-for-trend = 0.07). Ever douching was not associated with uterine cancer risk (HR = 1.0; 95% CI = 0.72, 1.5), with no evidence of a frequency dose-response (P = 0.96). The estimates were similar when we restricted to invasive endometrial cancers, but not when we further restricted to endometroid adenocarcinomas. CONCLUSION: The positive association we observed between talc use and uterine cancer risk is consistent with findings from previous prospective cohort studies of endometrial cancer. The relationships between uterine cancer and both douching and talc use merit further consideration, particularly as both exposures are preventable.

Increasing BMI is associated with both endometrioid and serous histotypes among endometrial rather than ovarian cancers: a case-to-case study.

AIM: Although obesity has been associated with endometrioid (type I) and, to a lesser extent, with serous (type II) endometrial cancer (EC), the association with the same histotypes of ovarian cancer (OC) remains unclear. Therefore, we intended to compare the role of BMI in carcinogenesis of endometrioid and the serous malignancies, at both ovarian and endometrial level. METHODS: A retrospective case-to-case study was performed in the University Hospital of Bologna (Italy), through the review of primary EC matched with the corresponding OC cases in the same period (1988-2017). RESULTS: We included 1052 women diagnosed with EC (n = 897 endometrioid, n = 52 serous) and 955 women affected by OC (n = 132 endometrioid, n = 627 serous). EC patients had higher median BMI than women diagnosed with OC (27.3 [23.4-31.9] vs 24.9 [21.7-27.5], p < 0.01). After controlling for confounding, 1 unit increase in BMI was associated with a 5% higher odds of endometrial as opposed to ovarian cancer (OR for ovarian as opposed to endometrial cancer 0.95; 95% CI 0.91-0.98, p = 0.004). CONCLUSIONS: Increasing BMI is associated with endometrial rather than ovarian cancer, among both serous and endometrioid histotypes.

Recurrence, death, and secondary malignancy after ovarian conservation for young women with early-stage low-grade endometrial cancer.

OBJECTIVE: To examine the association between ovarian conservation and oncologic outcome in surgically-treated young women with early-stage, low-grade endometrial cancer. METHODS: This multicenter retrospective study examined women aged <50 with stage I grade 1-2 endometrioid endometrial cancer who underwent primary surgery with hysterectomy from 2000 to 2014 (US cohort n = 1196, and Japan cohort n = 495). Recurrence patterns, survival, and the presence of a metachronous secondary malignancy were assessed based on ovarian conservation versus oophorectomy. RESULTS: During the study period, the ovarian conservation rate significantly increased in the US cohort from 5.4% to 16.4% (P = 0.020) whereas the rate was unchanged in the Japan cohort (6.3-8.7%, P = 0.787). In the US cohort, ovarian conservation was not associated with disease-free survival (hazard ratio [HR] 0.829, 95% confidence interval [CI] 0.188-3.663, P = 0.805), overall survival (HR not estimated, P = 0.981), or metachronous secondary malignancy (HR 1.787, 95% CI 0.603-5.295, P = 0.295). In the Japan cohort, ovarian conservation was associated with decreased disease-free survival (HR 5.214, 95% CI 1.557-17.464, P = 0.007) and an increased risk of a metachronous secondary malignancy, particularly ovarian cancer (HR 7.119, 95% CI 1.349-37.554, P = 0.021), but was not associated with overall survival (HR not estimated, P = 0.987). Ovarian recurrence or metachronous secondary ovarian cancer occurred after a median time of 5.9 years, and all cases were salvaged. CONCLUSION: Our study suggests that adoption of ovarian conservation in young women with early-stage low-grade endometrial cancer varies by population. Ovarian conservation for young women with early-stage, low-grade endometrial cancer may be potentially associated with increased risks of ovarian recurrence or metachronous secondary ovarian cancer in certain populations; nevertheless, ovarian conservation did not negatively impact overall survival.

Assessing endometrial cancer risk among US women: long-term trends using hysterectomy-adjusted analysis.

BACKGROUND: Commonly reported incidence rates for endometrial cancer fail to take into account both the large number of hysterectomies performed each year and the dynamic change in hysterectomy rate over the past decade. Large racial differences in premenopausal hysterectomy rates between Black and White women in the United States likely affect calculation of race-based risk. OBJECTIVES: The objectives of the study were to determine how the long-term trends in Black-White differences in endometrial cancer incidence and histology type have changed over time for women at risk. STUDY DESIGN: Using longitudinal Surveillance, Epidemiology, and End Results data from 1997 to 2014 and state-level hysterectomy prevalence from the Behavioral Risk Factor Surveillance System, we calculated hysterectomy-adjusted incidence rates of endometrial cancer and the proportion of high vs low-risk endometrial cancer, by race, over time. RESULTS: In women older than 50 years who have not had a hysterectomy, endometrial cancer incidence is 87 per 100,000 from 1997 to 2014. Among White women endometrial cancer incidence changed from 102 (1997-2001) to 86 (2012-2014) cases per 100,000, with a nonsignificant decreasing linear trend (adjusted risk ratio, 0.95; 95% confidence interval, 0.91-1.00; p=0.05). In contrast, incidence for Black women was 88 (1997-2001), 101 (2002-2006), 100 (2007-2011), and 102 (2012-2014) cases per 100,000 with no decreasing trend (adjusted risk ratio, 1.02; 95% confidence interval, 0.96-1.10, P = .449). High-risk histology increased among both groups (White: adjusted risk ratio, 1.06; 95% confidence interval, 1.01-1.11; P = .015; Black: adjusted risk ratio, 1.06; 95% confidence interval, 1.02-1.10, P = .007). Racial difference in the proportion of high-risk disease remained stable. CONCLUSION: Updated hysterectomy-adjusted incidence demonstrates that endometrial cancer is the second most common cancer among women older than 50 years with a uterus and that endometrial cancer has been more common among Black women compared with White women in the United States since 2002. A clinical approach of proactive communication and routine screening for early symptoms in the perimenopausal and menopausal years, especially among Black women, is warranted. These findings can also inform equitable distribution of research funding for endometrial cancer and serve to promote public awareness of this common cancer.

Hysterectomy-corrected rates of endometrial cancer among women younger than age 50 in the United States.

PURPOSE: This analysis describes the impact of hysterectomy on incidence rates and trends in endometrioid endometrial cancer in the United States among women of reproductive age. METHODS: Hysterectomy prevalence for states containing Surveillance, Epidemiology, and End Results (SEER) registry was estimated using data from the Behavioral Risk Factor Surveillance System (BRFSS) between 1992 and 2010. The population was adjusted for age, race, and calendar year strata. Age-adjusted incidence rates and trends of endometrial cancer among women age 20-49 corrected for hysterectomy were estimated. RESULTS: Hysterectomy prevalence varied by age, race, and ethnicity. Increasing incidence trends were observed, and were attenuated after correcting for hysterectomy. Among all women, the incidence was increasing 1.6% annually (95% CI 0.9, 2.3) and this increase was no longer significant after correction for hysterectomy (+ 0.7; 95% CI - 0.1, 1.5). Stage at diagnosis was similar with and without correction for hysterectomy. The largest increase in incidence over time was among Hispanic women; even after correction for hysterectomy, incidence was increasing (1.8%; 95% CI 0.2, 3.4) annually. CONCLUSION: Overall, endometrioid endometrial cancer incidence rates in the US remain stable among women of reproductive age. Routine reporting of endometrial cancer incidence does not accurately measure incidence among racial and ethnic minorities.