Non-endometrioid Endometrial Cancer Research Articles

Lymph-vascular Space Involvement and/or p53 Overexpression Correlated With the Clinical Outcome of Early-stage Endometrial Cancer Patients Treated With Adjuvant Vaginal Brachytherapy.

The majority of patients with endometrial cancer (EC) are diagnosed at an early stage and undergo primary surgery, followed by observation or adjuvant therapy according to risk factors on surgical samples. The objective of this study was to assess the correlation between a risk profile represented by the presence of substantial lymph-vascular space involvement (LVSI) and/or p53 overexpression and the clinical outcome of patients with early-stage endometrial cancer (EC) who received adjuvant vaginal brachytherapy (BT). This investigation assessed 79 patients who underwent hysterectomy, bilateral salpingo-oophorectomy, and pelvic and/o aortic lymphadenectomy or sentinel lymph node biopsy followed by hypofractionated (HDR)-vaginal BT, using 192Ir source, for stage I-II endometrioid (n=70) or non-endometrioid (n=9) EC. Thirty-four patients (43.0%) were considered to have an unfavorable risk profile defined by the presence of substantial LVSI and /or p53 overexpression. Five-year disease-free survival (DFS) and five-year overall survival (OS) were 93.7% and 95%, respectively. There was a significant correlation between unfavorable risk-profile and pelvic recurrence rate (p=0.002) and distant recurrence rate (p=0.017). Patients with abnormal p53 had a higher risk of local relapse (p=0.041). Substantial LVSI was strongly associated with pelvic recurrence (p=0.001) and distant metastasis (p<0.001). The presence of substantial LVSI and/or p53 overexpression strictly correlated with poor outcome of patients with early-stage EC and should be taken into consideration for better planning adjuvant treatment in this clinical setting.

Child and adult adiposity and subtype-specific endometrial cancer risk: a multivariable Mendelian randomisation study

Increased adiposity is a known risk factor for endometrial cancer (EC). This study aimed to disentangle the separate causal roles of child and adult adiposity on EC risk in adults, including endometrioid and non-endometrioid histological subtypes using multivariable Mendelian randomisation. These analyses employed genetic associations derived from UK Biobank as proxies for child and adult body size in 12,906 cases and 108,979 controls that participated in the Endometrial Cancer Association Consortium. In multivariable analyses, adult body size increased overall EC (OR 2.30, 95% CI 1.73–3.06) and endometrioid EC risk (OR 2.28, 95% CI 1.65–3.16), while child body size had minimal effect. In contrast, child body size (OR 2.26, 95% CI 1.03–4.99) but not adult body size increased non-endometrioid EC risk. As such, child adiposity has an indirect effect on endometrioid EC risk that is mediated by adult adiposity but has a direct effect on non-endometrioid EC risk that is independent of adult adiposity. These novel findings indicate that interventions targeting adiposity during distinct periods in life have a critical role in preventing subtype-specific EC.

7428 Oncologic Safety of Minimally Invasive Surgery in Non-Endometrioid Endometrial Cancer

<h3>Study Objective</h3> This study was aimed to compare the oncologic outcomes of patients with non-endometrioid endometrial cancer who underwent minimally invasive surgery with the outcomes of patients who underwent open surgery. <h3>Design</h3> retrospective study. <h3>Setting</h3> multi-institutional study. <h3>Patients or Participants</h3> patients with non-endometrioid endometrial cancer who were surgically staged by either minimally invasive surgery or open surgery. <h3>Interventions</h3> Oncologic outcomes of the patients were compared according to surgical approach. <h3>Measurements and Main Results</h3> 113 patients met the inclusion and exclusion criteria. 57 underwent minimally invasive surgery and 56 underwent open surgery. Patients who underwent minimally invasive surgery had smaller tumors (median size, 3.3 vs. 5.2%, <i>p</i>=0.0001) and a lower lymphovascular space invasion rate (29.8% vs. 48.2%, <i>p</i>=0.045). In the overall population, the numbers and rate of recurrence were significantly higher in the open surgery group (<i>p</i> = 0.016). In multivariate analysis, disease stage and tumor size were associated with DFS in contrast to surgical procedure. <h3>Conclusion</h3> Minimally invasive surgery showed similar survival outcomes when compared to open surgery in non-endometrioid endometrial cancer patients, irrespective of disease stage. When minimally invasive surgery is managed by expert surgeons, non-endometrioid histological subtypes should not be considered a contraindication for minimally invasive surgery.

The role of fat distribution and inflammation in the origin of endometrial cancer, study protocol of the ENDOCRINE study.

Obesity is a growing problem worldwide, especially in countries with improved socioeconomic circumstances. Also, in the Netherlands the incidence of overweight and obesity is rising. There is increasing evidence on the association between obesity and tumorigenesis. Of all cancer types, endometrial cancer (EC) has the strongest positive correlation with obesity. Obesity is generally defined as a body mass index (BMI) >30, yet does not cover the differences in fat distribution in visceral and subcutaneous compartments. Visceral fat is assumed to be relatively more metabolically active and likely negative prognostic biomarker in non-endometrioid EC. Whereas subcutaneous fat is mainly responsible for oestrogen production through increased aromatase activity. The aim of this study is to compare hormone levels and inflammatory markers after bilateral salpingo-oophorectomy (BSO) in obese and non-obese patients. Secondary objectives are to compare the effect of fat distribution and diagnosis (benign vs. EC) on the observed changes in hormone levels and inflammatory markers, and to compare the effect of BSO on menopausal complaints. Prospective multicentre observational cohort study. A total of 160 patients will be included, of which 80 patients with a normal BMI (18-25 kg/m2) and 80 patients with an obese BMI >32-35 kg/m2. Preoperative abdominal CT will be performed and fasting venous blood samples are obtained for hormone levels and inflammation markers analysis. During surgery, adipose tissue biopsies of subcutaneous and visceral (omental and intestinal epiploic fat) compartments will be collected and stored fresh frozen. In addition a fasting blood draw six weeks after surgery will be obtained. All subjects will fill in two questionnaires before surgery and one after surgery. We hypothesize that BMI, the type of fat distribution, and possibly the underlying pathology significantly influence in hormone levels, and systemic inflammation changes after BSO. Previous studies have found several clues for a relationship between obesity and endometrial cancer. We expect that our study will contribute to pinpoint the exact differences between 'healthy obesity' and 'unhealthy obesity' and will help to identify patients that are more at risk of developing cancer (or possibly suffer from other related problems such as cardiovascular problems e.g.).

Not all stage I and II endometrial cancers are created equal: Recurrence-free survival and cause-specific survival after observation or vaginal brachytherapy alone in all subgroups of early-stage high-intermediate and high-risk endometrial cancer

ObjectiveTo evaluate recurrence-free survival (RFS) and cause-specific survival (CSS) after observation or vaginal brachytherapy (VB) alone in all subgroups of early-stage high-intermediate (HIR) and high-risk endometrial cancer (EC). MethodsWe identified patients with stage I HIR (GOG-249 criteria) and stage II endometrioid EC, and stage I and II non-endometrioid EC who underwent surgery at Mayo Clinic and Cleveland Clinic between 1999 and 2016. Three-year RFS and CSS after observation or VB only were estimated in 16 subgroups defined by risk factors. ResultsAmong 4156 ECs, we identified 447 (10.8%) stage I endometrioid HIR, 52 (1.3%) stage II endometrioid, 350 (8.4%) stage I non-endometrioid, and 17 (0.4%) stage II non-endometrioid ECs; observation or VB alone was applied in 349 (78.1%), 24 (46.2%), 187 (53.4%), and 2 (11.8%) patients, respectively. After observation or VB, stage I HIR endometrioid EC subgroups with <2 factors among grade 3, LVSI, or stage IB had a 3-year CSS >95% (lower 95% confidence intervals limit: 89.8%), whereas subgroups with ≥2 factors had poorer outcomes. No EC-related deaths after 3 years were reported in 97 stage IA non-endometrioid ECs without myometrial invasion. Stage II ECs had poor outcomes regardless of histology. ConclusionsObservation or VB only may be sufficient in stage I endometrioid HIR ECs with <2 factors among grade 3, LVSI, or IB and in stage IA non-endometrioid ECs without myometrial invasion. Stratification of early-stage HIR and high-risk ECs into risk subgroups potentially alleviates the overtreatment and undertreatment risk and should be considered in future research.

Association of APOBEC3A/B deletion variant with endometrial cancer risk in Norwegian population: A case-control study (242)

<b>Objectives:</b> APOBEC3 family of proteins play important roles in intrinsic responses to viral infection by introducing mutations into the viral nucleic acids. APOBEC3 activity targeting the host cell's DNA may lead to mutations contributing to tumorigenesis. Uterine cancers are found to be linked with three APOBEC associated signatures; single-base substitution signatures 2 and -13 and double-base substitution signature 11. A germline deletion of 30Kb in chromosome 22 affecting the APOBEC3A and -B genes leads to the formation of a hybrid transcript, APOBEC3A/B, found to be more stable than the wild-type APOBEC3A and causes more DNA damage through higher protein levels. To the best of our knowledge, the potential association between the APOBEC3A/B deletion variant and the risk of endometrial cancer has not yet been assessed. This study aimed to evaluate the APOBEC3A/B deletion as a potential risk modulating factor for endometrial cancer. <b>Methods:</b> DNA extracted from blood samples of Norwegian (Caucasian) women diagnosed with primary uterine adenocarcinoma (<i>n</i>=1,470), and healthy controls (<i>n</i>=1,918) were screened for germline APOBEC3A/B deletion variant using quantitative polymerase chain reaction high-resolution melting (qPCR-HMR) curves. For technical validation, 35.4% of cases were genotyped for SNP rs12628403 (Chr 22:38962032), an SNP in proximity to the APOBEC3A/B-deletion start point that is found in strong linkage disequilibrium with the deletion allele. The potential difference in results from APOBEC3A/B deletion and rs12628403-analyses were considered negligible due to a very low recombination rate of 5.8x10-3. <b>Results:</b> Cases and controls were in Hardy-Weinberg equilibrium for genotype distribution (p=0.78 and p>0.4, with a MAF of 0.072 and 0.094, respectively). Our study cohort showed a reduced risk of endometrial cancer in dominant and allele models (OR: 0.75, 95 % CI: 0.62-0.91, p=0.003 and OR: 0.75, 95 % CI: 0.63-0.90, p=0.0002, respectively). In a subgroup analysis by histology, endometrioid endometrial cancer showed similar patterns (dominant model: OR: 0.64, 95% CI: 0.51-0.79, p=0.1x10-3 and allele model: OR: 0.64, 95% CI: 0.52-0.79, p=0.1x10-3). No clear risk association was observed in non-endometrioid endometrial cancer subtype. Among age subgroups generated with a 10-year cut-off, dominant and allele models yielded a significantly reduced cancer risk in individuals in the age range 50-59 (OR: 0.51, 95% CI: 0.33-0.78, p=0.002 and OR: 0.54, 95% CI: 0.35-0.81, p=0.002, respectively) and 60-69 (OR = 0.62, 95% CI=0.43-0.88, p=0.8x10-3 and OR=0.62, CI=0.44-0.88, p=0.005, respectively). <b>Conclusions:</b> APOBEC3A/B deletion variant is associated with reduced endometrial cancer risk in Norwegian women.

Embryological Aspects and Anatomical Variations of the Inferior Vena Cava – Its Importance in Gynecologic Oncology Surgery

Summary Surgical procedures of the retroperitoneum are often performed in gynecologic oncology surgery clinics. The most complex among them is paraaortic lymphadenectomy. It is generally performed in cases of bulky lymph nodes in ovarian carcinomas and sarcomas to achieve optimal cytoreduction. In the early stages of ovarian cancer, type II non-endometrioid endometrial cancer, and in advanced stages of cervical cancer, paraaortic lymphadenectomy is an integral part of staging. Moreover, the retroperitoneum is approached in cases of retroperitoneal gynecologic sarcomas. The largest vessels of the human body – the inferior vena cava and the abdominal aorta are localized in the retroperitoneum. Therefore, iatrogenic vessel injury during oncogynecological surgery is more likely to affect the inferior vena cava. Anatomical variations of the vein additionally increase the risk of vascular lesions. Therefore, surgeons should be aware of possible anatomical variations. The present article aimed to highlight the heterogeneity of anatomical variations of the inferior vena cava related to gynecologic oncology surgery. Embryogenesis of the vein and its variations are also discussed. Additionally, some anomalies of the ureter, associated with the embryogenesis of the inferior vena cava, are mentioned.

Increased survival in non-endometrioid endometrial cancer after introducing lymphadenectomy and tailoring radiotherapy – A population-based cohort study

ObjectiveTo investigate recurrence and survival in non-endometrioid endometrial cancer in a population-based cohort and evaluate the implementation of the first national guidelines (NGEC) recommending pelvic and paraaortic lymphadenectomy for surgical staging and tailored adjuvant therapy. MethodsA population-based cohort study that used the Swedish quality registry for gynaecological cancer for the identification of all women with early-stage non-endometrioid endometrial cancer between 2010 and 2017. Five-year overall (OS) and disease-free survival (DFS) were calculated using the Kaplan–Meier method. The Cox proportional hazards regression model was used to evaluate the effect of age, FIGO stage, primary treatment and lymph node dissection on DFS. ResultsThere were 228 patients included in the study cohort and 67 (29%) patients had a recurrence within five years. In the recurrence cohort, the OS was 13.4% (95%CI:7.3–24.7) compared to 88.5% (95%CI:83.4–93.9) if no recurrence occurred (log-rank p < 0.001). The DFS for the complete cohort was 61.9% (95%CI:55.7–68.7).The OS before implementation of NGEC was 57.3% (95%CI:48.2–68.1) and the DFS was 52.1% (95%CI:43.0–63.1) compared to an OS of 72.0% (95%CI:64.2–80.7; log-rank p = 0.018) and a DFS of 70.1% (95%CI:62.4–78.7; log-rank p = 0.008) after implementing NGEC. Patients received adjuvant radiotherapy in 92.7% before and 42.4% after NGEC implementation (p < 0.001). In the multivariable regression analysis, age, FIGO stage and lymph node dissection were found to be significant prognostic factors, where having a lymph node dissection decreased the risk of recurrence or death with a HR of 0.58 (95%CI:0.33–1.00). ConclusionIn this population-based cohort of preoperative early-stage non-endometrioid EC, a significant improvement in survival was seen after NGEC implementation where lymph node staging for tailoring adjuvant therapy was introduced and less pelvic radiotherapy was given.

Pathologic primary tumor factors associated with risk of lymph node involvement in patients with non-endometrioid endometrial cancer

Purpose/objectivesLymph node (LN) involvement is an important factor in guiding adjuvant treatment for patients with endometrial cancer. Risk factors for LN involvement are fairly well-established for endometrial adenocarcinoma, but it is not as well defined whether these factors similarly predict LN positivity in less common histologies. Materials/methodsPatients diagnosed with pathologic T1-T2 carcinosarcoma, clear cell, uterine papillary serous carcinoma (UPSC), and mixed histologic type endometrial cancer between 2004 and 2016 undergoing primary surgery with at least 1 lymph node sampled in the National Cancer Data Base were identified. Logistic regression was performed to identify primary pathologic tumor predictors of LN positivity. Nomograms were created to predict overall, pelvic only, and paraaortic with or without pelvic LN involvement. ResultsAmong 11,390 patients included, 1950 (18%) were node positive. On multivariable analysis, increasing pathologic tumor stage (pT2 versus pT1a, odds ratio [OR] 3.63, 95% confidence interval [CI] 3.15–4.18, p < 0.001), increase in tumor size per centimeter (OR 1.08, 95% CI 1.06–1.10, p < 0.001), and the presence of lymphovascular invasion (LVI) (OR 4.97, 95% CI 4.43–5.57, p < 0.001) were predictive of overall LN positivity. Relative to carcinosarcoma, both clear cell (OR 1.54, 95% CI 1.22–1.95, p < 0.001) and UPSC (OR 1.73, 95% CI 1.48–2.02, p < 0.001) histology were significantly associated with a higher risk of LN positivity while mixed histology was not (OR 1.07, 95% CI 0.92–1.24, p = 0.42). ConclusionAmong patients with non-endometrioid endometrial cancer, predictors of LN positivity are similar to endometrial adenocarcinoma. The nomograms provided could be helpful in making adjuvant treatment decisions for these less common histologies.

Anatomical distribution of sentinel lymph nodes in patients with endometrial cancer: a multicenter study

ObjectiveSentinel lymph node (SLN) mapping represents the standard approach in uterine confined endometrial cancer patients. The aim of this study was to evaluate the anatomical distribution of SLNs and the...

Diagnostic accuracy of sentinel node biopsy in non-endometrioid, high-grade and/or deep myoinvasive endometrial cancer: A Turkish gynecologic oncology group study (TRSGO-SLN-006)

IntroductionThis study aimed to evaluate the diagnostic accuracy of the sentinel lymph node (SLN) mapping algorithm in high-risk endometrial cancer patients. MethodsTwo hundred forty-four patients with non-endometrioid histology, grade 3 endometrioid tumors and/or tumors with deep myometrial invasion were enrolled in this retrospective, multicentric study. After removal of SLNs, all patients underwent pelvic ± paraaortic lymphadenectomy. Operations were performed via laparotomy, laparoscopy or robotic surgery. Indocyanine green (ICG) and methylene blue (MB) were used as tracers. SLN detection rate, sensitivity, negative predictive value (NPV) and false-negative rate (FNR) were calculated. ResultsSurgeries were performed via laparotomy in 132 (54.1%) patients and 152 (62.3%) underwent both bilateral pelvic and paraaortic lymphadenectomy. At least 1 SLN was detected in 222 (91%) patients. Fifty-five (22.5%) patients had lymphatic metastasis and 45 patients had at least 1 metastatic SLN. Lymphatic metastases were detected by side-specific lymphadenectomy in 8 patients and 2 patients had isolated paraaortic metastasis. Overall sensitivity, NPV and FNR of SLN biopsy were 81.8%, 95% and 18.2%, respectively. By applying SLN algorithm steps, sensitivity and NPV improved to 96.4% and 98.9%, respectively. For grade 3 tumors, sensitivity, NPV and FNR of the SLN algorithm were 97.1%, 98.9% and 2.9%. ConclusionSLN algorithm had high diagnostic accuracy in high-risk endometrial cancer. All pelvic metastases were detected by the SLN algorithm and the isolated paraaortic metastasis rate was ignorable. But long-term survival studies are necessary before this approach becomes standard of care.

Non-endometrioid endometrial cancer: Analysis of different adjuvant treatment modalities

BackgroundAdjuvant treatment for endometrial carcinoma (EC) is decided based on risk assessment. Tumors of non-endometrioid (NE) histology are classified as high-risk and adjuvant treatment is recommended. Materials and MethodsWe analyzed retrospectively all NEEC patients treated in two Portuguese oncology centers, between 2009 and 2018. Comparison of adjuvant modalities were performed by overall survival (OS) and disease-free survival (DFS) analysis. ResultsA total of 66 patients were included, with mean age 69 years. Serous histology was found in 34 patients (51.5%), clear-cell in 13 (19.7%) and carcinosarcoma in 18 (27.3%). Based on FIGO staging-system, 34 (51.5%) patients were diagnosed at stages III-IV. Following surgery, no further treatment was performed in 16 patients (24.4%), 11 (16.7%) received isolated chemotherapy (CT), 11 (16.7%) isolated radiotherapy (RT) and 28 (42.4%) combination therapy (CT+RT). Kaplan-Meier analysis showed higher median (m)DFS in the CT+RT group: 30.7 months (m) compared to RT alone: 14.1 m. The mDFS of the isolated CT group was 10.8 m and for patients with no further treatment it was 5.7 m, p = 0.03. Median OS was also increased in the combination group CT+RT (78.3 m) compared to isolated RT (64.3 m), isolated CT (37.3 m) and no further treatment (46.7 m), p=0.005. Multivariate Cox-regression using CT+RT as reference, showed hazard-ratio of 3.5 (p = 0.05) and 4.5 (p = 0.01) for the CT and for no-treatment group respectively. ConclusionsIn NEEC patients, DFS and OS analysis showed better prognosis in combination of CT+RT. Patients that underwent only RT had better survival outcomes when compared to those treated with CT only.

Does lymph node dissection impact adjuvant treatment or survival outcomes in high-risk endometrial cancers?

Studies have shown that lymphadenectomy does not improve overall survival outcomes in patients with type I, low risk endometrial cancers. There is good data supporting that sentinel node mapping has a high detection rate and accuracy in high-risk uterine cancers, however its prognostic and adjuvant treatment implications have not been well explored. We aimed to evaluate the overall survival and adjuvant therapies received by patients undergoing complete versus sentinel lymph node dissection for a diagnosis of grade 3 endometrioid or high-grade non-endometrioid endometrial cancer.

Pre-operative wait times in high-grade non-endometrioid endometrial cancer: Do surgical delays impact patient survival?

ObjectivePractice guidelines advocating for regionalization of endometrial cancer surgery to gynecologic oncologists practicing in designated gynecologic oncology centres were published in Ontario in June 2013. Our objectives were to determine whether this policy affected surgical wait times, and whether longer wait time to surgery is a predictor of survival in high grade endometrial cancer patients. MethodsThis was a population-based retrospective cohort study, which included patients diagnosed with high-grade non-endometrioid endometrial cancer who had a hysterectomy between 2003 and 2017. Multivariable Cox proportional hazards regression with a spline function was used to model the relationship between surgical wait time and overall survival (OS). ResultsWe identified 3518 patients who underwent hysterectomy for high-grade non-endometrioid endometrial cancer. Patients who had surgery with a gynecologic oncologist had a median surgical wait time from diagnosis to hysterectomy of 53 days compared to 57 days pre-regionalization (p = 0.0007), and from first gynecologic oncology consultation to hysterectomy of 29 days compared to 32 days pre-regionalization (p = 0.0006). Survival was inferior for patients who had surgery within 14 days of diagnosis (HR death 2.7 for 1–7 days, 95% CI 1.61–4.51, and HR death 1.96 for 8–14 days, 95% CI 1.50–2.57), reflective of disease severity. Decreased survival occurred with surgical wait times of more than 45 days from the patient's first gynecologic oncology appointment (HR death 1.19 for 46–60 days, 95% CI 1.04–1.36, and HR death 1.42 for 61–75 days, 95% CI 1.11–1.83). ConclusionsRegionalization of surgery for high-grade endometrial cancer has not had an impact on surgical wait times. Patients who have surgery more than 45 days after surgical consultation have reduced survival.

Sialic acids in gynecological cancer development and progression: Impact on diagnosis and treatment.

Gynecological cancers are in the top 10 of most common cancers in women. Survival and outcome are strongly related to the stage at diagnosis. Therefore, early diagnosis is essential in reducing morbidity and mortality. The high mortality rate of gynecological cancers can mainly be attributed to ovarian cancer (OC). OC is commonly diagnosed at an advanced stage due to a lack of proper screening tools allowing early detection. Endometrial cancer (EC) on the contrary, is mostly diagnosed at an early stage and has, in general, better outcomes. The incidence of nonendometrioid EC has increased in the last decade, displaying a shared tumor biology with OC and consequently significantly worse outcome. New approaches allowing detection of gynecological cancers in an early stage are therefore desired. Recent studies on cancer biology have shown the relevance of altered glycosylation in the occurrence and progression of cancer. The aberrant expression of sialic acid, a specific carbohydrate terminating glycoproteins and glycolipids on the cell‐surface, is frequently correlated with malignancy. We aimed to determine the current understanding of sialic acid function in different gynecological cancers to identify the gaps in knowledge and its potential use for new diagnostic and therapeutic avenues. Therefore we performed a review on current literature focusing on studies where sialylation was linked to gynecological cancers. The identified studies showed elevated levels of sialic acid in serum, tissue and sialylated antigens in most patients with gynecological cancers, underlining its potential for diagnosis.

The Genetic Association of Polycystic Ovary Syndrome and the Risk of Endometrial Cancer: A Mendelian Randomization Study.

The association between polycystic ovary syndrome (PCOS) and endometrial cancer remains unclear. We aimed to investigate the causal association between genetically predicted PCOS and endometrial cancer risk in two ethnic groups through a two-sample Mendelian randomization (MR) approach. Our study includes 13 single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for PCOS in Europeans, and another 13 SNPs are used as IVs for PCOS in Asians. Outcome data were obtained from the largest published meta-GWAS of European ancestry to date, as well as from the BioBank Japan Project of Asian ancestry. Our study demonstrates that genetically predicted PCOS is not causally associated with the risk of overall endometrial cancer in either Europeans or Asians (odds ratio (OR) = 0.93, 95% confidence interval (CI) = 0.85–1.01, p = 0.09 and OR = 0.98, 95% CI 0.84–1.13, p = 0.75, respectively). Subgroup analyses according to histotype further illustrate that PCOS might not be associated with the risk of either endometrioid endometrial cancer or non-endometrioid endometrial cancer in European ancestry. No pleiotropy is found in our study, and a sensitivity analysis shows similar results. Our results indicate that genetically predicted PCOS might not be associated with the risk of endometrial cancer.

Oncologic safety of minimally invasive surgery in non-endometrioid endometrial cancer

ObjectiveThis study was aimed to compare the oncologic outcomes of patients with non-endometrioid endometrial cancer who underwent minimally invasive surgery with the outcomes of patients who underwent open surgery. MethodThis is a retrospective, multi-institutional study of patients with non-endometrioid endometrial cancer who were surgically staged by either minimally invasive surgery or open surgery. Oncologic outcomes of the patients were compared according to surgical approach. Results113 patients met the inclusion and exclusion criteria. 57 underwent minimally invasive surgery and 56 underwent open surgery. Patients who underwent minimally invasive surgery had smaller tumors (median size, 3.3 vs. 5.2%, p = 0.0001) and a lower lymphovascular space invasion rate (29.8% vs. 48.2%, p = 0.045). In the overall population, the numbers and rate of recurrence were significantly higher in the open surgery group (p = 0.016). In multivariate analysis, disease stage and tumor size were associated with DFS in contrast to surgical procedure. ConclusionMinimally invasive surgery showed similar survival outcomes when compared to open surgery in non-endometrioid endometrial cancer patients, irrespective of disease stage. When minimally invasive surgery is managed by expert surgeons, non-endometrioid histological subtypes should not be considered a contraindication for minimally invasive surgery.

Factors predicting morbidity in surgically-staged high-risk endometrial cancer patients

ObjectiveTo investigate factors predicting the risk of developing 90-day postoperative complications and lymphatic-specific morbidity in patients undergoing surgical staging for high-risk endometrial cancer. MethodsThis is a multi-institutional retrospective cohort study. Patients affected by apparent early-stage high-risk endometrial cancer (endometrioid FIGO grade 3 with deep myometrial invasion and non-endometrioid endometrial cancer) undergoing surgical staging between 2007 and 2019. Complications were graded according to the Clavien-Dindo classification system. Martin criteria were applied to improve quality of complications reporting. ResultsCharts of 279 patients were evaluated. Lymphadenectomy, sentinel node mapping (SNM), and SNM followed by back-up lymphadenectomy were performed in 83 (29.7%), 50 (17.9%), and 146 (52.4%) patients, respectively. The former group of patients included 13 patients who had lymphadenectomy after the failure of the SNM technique. Thirteen (4.6%) patients developed severe postoperative events (grade 3 or worse). At multivariate analysis, body mass index (OR: 1.08 (95%CI: 1.01, 1.17)) and open abdominal surgery (OR: 2.27 (95%CI: 1.02, 5.32)) were the two independent factors predictive of surgery-related morbidity. Seven severe lymphatic complications occurred. The adoption of laparoscopic approach (p < 0.001, log-rank test) and SNM (p = 0.038, log-rank test) correlated with a lower risk of developing surgery-related events. Independently, open abdominal surgery was associated with an increased risk of developing lymphatic morbidity (OR: 37.4 (95%CI: 4.38, 319.5); p = 0.001). ConclusionThe adoption of the laparoscopic approach and SNM technique were associated with lower 90-day complication rates than open surgery in high-risk endometrial cancer undergoing staging surgery.

Preoperative wait times in high-grade endometrial cancer: do surgical delays impact patient survival?

<h3>Objectives:</h3> Practice guidelines advocating for the regionalization of endometrial cancer surgery to gynecologic oncologists practicing in designated gynecologic oncology centres were released by Cancer Care Ontario in June 2013. We sought to determine the impact this policy had on contemporary surgical wait times. Moreover, a discussion about the impact of delays in treatment has never been more timely than in the context of the current COVID19 pandemic, which has burdened health care systems around the world. Our primary objective was to establish whether longer wait time to surgery is a predictor of survival in patients with high grade endometrial cancer. <h3>Methods:</h3> This was a retrospective cohort study, which included patients diagnosed with non-endometrioid high-grade endometrial cancer (serous, carcinosarcoma, clear cell, and undifferentiated) between 2003 and 2017. A total of 2 regionalization periods were defined, before and after January 2014 to allow 6 months for knowledge translation after guideline publication. Patients were identified in population-based administrative provincial data sources. Multivariable Cox proportional hazards regression with a spline function was used to model the relationship between wait time and overall survival, as measured from time of surgery. <h3>Results:</h3> We identified 3518 patients with high grade endometrial cancer. Median wait time between diagnosis and surgery for the entire cohort did not significantly change with regionalization of care (50 vs 52 days, p=0.14). Patients who had surgery with a gynecologic oncologist had a median surgical wait time from diagnosis to hysterectomy of 55 days compared to 59 days pre-regionalization (p=0.0002), and from first gynecologic oncology consultation to hysterectomy of 29 days compared to 32 days pre-regionalization (p=0.0006). Survival was worst for patients who had surgery within 14 days of diagnosis (HR death 2.7, 95% CI 1.61-4.51 for 1-7 days and HR death 1.96, 95% CI 1.5-2.57 for 8-14 days), indicating disease severity. Decreased survival occurred with surgical wait times of more than 45 days from the patient's first gynecologic-oncology appointment (HR death 1.19, 95% CI 1.04-1.36 for 46-60 days and HR death 1.42, 95% CI 1.11-1.82). <h3>Conclusions:</h3> Regionalization of surgery for high grade endometrial cancer has not had a negative impact on surgical wait times. Impact on survival is seen with patients who have surgery more than 45 days after surgical consultation.

Estimated Performance of Transvaginal Ultrasonography for Evaluation of Postmenopausal Bleeding in a Simulated Cohort of Black and White Women in the US

Black women in the US with endometrial cancer (EC) are more likely to be diagnosed with advanced-stage disease independent of insured status and histologic type. The most common way of diagnosing EC at early stages is through screening of people with postmenopausal bleeding to detect endometrial thickness (ET). This approach may disproportionately underperform in Black women secondary to a higher prevalence of fibroids and nonendometrioid EC in this population, both of which affect the quality of ET measurement. To compare the performance of recommended transvaginal ultrasonography (TVUS) ET thresholds as a screening method to prompt endometrial biopsy by race in a simulated cohort of symptomatic women. In a simulated retrospective cohort study, based on data from Surveillance, Epidemiology, and End Results (SEER) national cancer registry 2012-2016; the US census; and published estimates of ET distribution and fibroid prevalence, diagnostic test characteristics of the 3-mm or more, 4-mm or more, and 5-mm or more ET thresholds for biopsy to capture EC diagnoses were calculated. The simulated cohort was constructed from February 2, 2020 (date of access to SEER data), to August 31, 2020. Analysis occurred from September 30, 2020, to March 30, 2021, including the primary analysis and the sensitivity calculations. The main outcome measured was accuracy of the TVUS ET threshold to accurately identify cases of EC, measured by sensitivity, negative predictive value, and area under the curve (AUC). A total of 367 073 simulated Black and White women with postmenopausal bleeding were evaluated, including 36 708 with EC. Among Black women, the currently recommended 4-mm or greater ET threshold prompted biopsy for fewer than half of EC cases (sensitivity, 47.5%; 95% CI, 46.0%-49.0%); of women referred for biopsy, 13.1% were EC cases (positive predictive value, 13.1%; 95% CI, 12.5%-13.6%). The AUC for the 4-mm or more threshold was 0.57 (95% CI, 0.56-0.57). In contrast, among the White women, the 4-mm or more threshold led to biopsy for most with EC (sensitivity, 87.9%; 95% CI, 87.6%-88.3%). Of those referred for biopsy, 14.6% had EC (positive predictive value, 14.6%; 95% CI, 14.4%-14.7%); AUC was 0.73 (95% CI, 0.73-0.74). The same variations held for the 3-mm or more and 5-mm or more ET thresholds: sensitivity, positive predictive value, and AUC were consistently lower for Black women than White women. The findings of this simulated cohort study suggest that use of ET as measured by TVUS to determine the need for EC diagnostic testing in symptomatic women may exacerbate racial disparities in EC stage at diagnosis. In simulated data, TVUS ET screening missed almost 5 times more cases of EC among Black women vs White women owing to the greater prevalence of fibroids and nonendometrioid histologic type in Black women.