Lower Uterine Segment Involvement Research Articles

Prognostic values of tumor size and location in early stage endometrial cancer patients who received radiotherapy.

To investigate the correlation between tumor size, tumor location, and prognosis in patients with early-stage endometrial cancer (EC) receiving adjuvant radiotherapy. Data of patients who had been treated for stage I-II EC from March 1999 to September 2017 in 13 tertiary hospitals in China was screened. Cox regression analysis was performed to investigate associations between tumor size, tumor location, and other clinical or pathological factors with cancer-specific survival (CSS) and distant metastasis failure-free survival (DMFS). The relationship between tumor size as a continuous variable and prognosis was demonstrated by restricted cubic splines. Prognostic models were constructed as nomograms and evaluated by Harrell's C-index, calibration curves and receiver operating characteristic (ROC) curves. The study cohort comprised 805 patients with a median follow-up of 61 months and a median tumor size of 3.0 cm (range 0.2-15.0 cm). Lower uterine segment involvement (LUSI) was found in 243 patients (30.2%). Tumor size and LUSI were identified to be independent prognostic factors for CSS. Further, tumor size was an independent predictor of DMFS. A broadly positive relationship between poor survival and tumor size as a continuous variable was visualized in terms of hazard ratios. Nomograms constructed and evaluated for CSS and DMFS had satisfactory calibration curves and C-indexes of 0.847 and 0.716, respectively. The area under the ROC curves for 3- and 5-year ROC ranged from 0.718 to 0.890. Tumor size and LUSI are independent prognostic factors in early-stage EC patients who have received radiotherapy. Integrating these variables into prognostic models would improve predictive ability.

Improving locoregional outcome in high-intermediate-risk and high-risk stage I endometrial cancer with surgical staging followed by brachytherapy.

PurposeThis study aims to assess the locoregional efficacy of postoperative vaginal brachytherapy (VBT) alone in patients undergoing surgical staging for early-stage high-intermediate-risk (HIR) and high-risk (HR) endometrial cancer. Materials and MethodsOne hundred and four patients with early-stage HIR and HR endometrial cancer who underwent surgical staging were treated with adjuvant VBT alone. The patients with stage Ib, grade I–III, stage Ia, grade III, lower uterine segment involvement, and lymphovascular invasion (LVI) were included to study. ResultsThe 5- and 10-year overall survival (OS) rates were 87% and 76%, respectively. The 5- and 10-year DFS rates were 86% and 86%, respectively. Among the patients, 92% had endometrioid adenocarcinoma, 2% had undifferentiated carcinoma, 2% had serous papillary carcinoma, and 4% had clear-cell carcinoma. Of the patients, 63% had stage Ib disease, while 37% had stage Ia disease. None of the patients had vaginal or pelvic lymph node recurrence, whereas two had para-aortic lymph node metastasis, one had surgical scar recurrence, one had para-aortic lymph node and brain metastasis, and one had lung metastasis. The presence of lymphatic invasion was found to be a statistically significant prognostic factor for increased distant metastasis rates (p = 0.020). Lymphatic invasion was also regarded as an independent prognostic factor for metastasis-free survival (p = 0.044). ConclusionOur study results suggest that postoperative VBT alone is an effective and safe treatment modality with low complication in patients undergoing surgical staging for HIR and HR endometrial cancer.

The Association between Lower Uterine Segment Involvement in Corpus Located Endometrioid Adenocarcinoma with the (International Federation of Gynecology and Obstetrics) Grade and Stage

BACKGROUND: Although lower uterine segment (LUS) is regarded as an anatomically defined part that possess some histological differences, it is involvement by carcinoma have not been included in the criteria for definition in the staging system for endometrial carcinoma and there are few conflicting data focused on the effect of LUS involvement as a prognostic factor in endometrial cancer. AIM: To find the association between LUS involvement in corpus located endometrioid carcinoma with the grading and staging system established by the international federation of gynecology and obstetrics (FIGO). METHODS: This was a retrospective study involving data collected from achieves of histopathology departments of teaching laboratories within successive 4 years period in Medical City complex at Bagdad. Pathological analysis of 70 hysterectomy specimens of corpus located endometriod adenocarcinoma was done, histological sections from each case of endometrioid adenocarcinoma carcinoma were microscopically reviewed for appropriate grading and staging, in addition, meticulous search was applied for histological finding consistent with LUS involvement. The statistical comparison between the results was done using either independent sample t-test (for continuous data; mean ± SD) or Chi-square test at a significant p < 0.05. RESULTS: The study enrolled 70 histological samples of endometrioid adenocarcinoma, the majority of the samples were of low grade and stage at presentation. Of total sample, 46 (65.71%) showed LUS involvement by tumor cells. There was a significant statistical relationship between LUS involvement and FIGO stage while a non-significant statistical association with FIGO grade was found. CONCLUSION: LUS involvement by corpus located endometrioid adenocarcinoma is associated with an advanced FIGO stage at presentation while non-significant relationship was found between patient age and tumor grade.

Screening of Lynch syndrome in endometrial cancer in Iranian population with mismatch repair protein by immunohistochemistry.

Lynch syndrome (LS) is one of the commonest genetic cancer syndromes, with an incidence rate of 1 per 250-1000 population. The aim of this study was to evaluate the frequency and characteristics of MMR deficiency in endometrial cancer in Iranian women. One hundred endometrial carcinoma cases who referred to the gynecological oncology clinic of Imam Hossein Medical Center located in Tehran, Iran, from 2018 to 2020 were included in the study. Immunohistochemistry (IHC) evaluation was performed mainly on the hysterectomy specimens of all endometrial cancer (EC) patients to assess MMR proteins (MLH1, MSH2, MSH6, and PMS2) expression. A total of 23 out of 100 (23%) cases were identified through IHC screening to be MMR-deficient. The most common types were loss of MLH1/PMS2 (17.4%) and solitary MSH2 (17.4%) expressions followed by PMS2/MSH2 loss (13%). MMR deficiency (dMMR) histopathology was significantly overrepresented in patients with family history of cancer or Lynch syndrome (LS) associated cancers (p-values of 0.016 and 0.005, respectively). The rate of myometrial invasion and lower uterine segment involvement were also significantly higher in dMMR EC patients compared to MMR-intact EC (p-value of 0.021 and 0.018, respectively). MMR deficiency, observed in 23% of endometrial cancer cases, was associated with higher rates of poor prognostic factors including myometrial invasion and lower uterine segment involvement. The presence of positive family history of cancer and family history of LS-associated cancer increased the probability of MMR-deficiency in endometrioid endometrial cancer to 47% and 70%, respectively.

Diffusion-weighted MRI at 3T in Endometrial Cancer: Correlation of Apparent Diffusion Coefficient with Histopathological Prognostic Parameters

To evaluate the value of apparent diffusion coefficient (ADC) for the differentiation of histological subtypes in endometrial cancer, and to assess if ADC values correlate with histopathological parameters.Descriptive study.Department of Radiology, Faculty of Medicine, Ondokuz Mayis University between January 2016 and December 2019.Eighty-three patients (mean age: 60.28 ± 9.07) with endometrial cancer underwent diffusion-weighted imaging (DWI) at 3T before surgery. The mean ADC (ADCmean) and minimum ADC (ADCmin) values of the tumours were assessed to predict histological subtype of endometrial cancer, grade of tumour, presence of myometrial invasion, lower uterine segment involvement, cervical involvement, lymphovascular invasion, and lymph node metastasis.Sixty patients (72.3%) were diagnosed with endometrioid carcinoma, and 23 patients (27.7%) were diagnosed with non-endometrioid carcinoma. The median ADCmean/ADCmin of endometrioid and non-endometrioid tumours were 0.72/0.58 ×10-3 mm2/s and 0.82/0.63 ×10-3 mm2/s, respectively. ADCmean and ADCmin were significantly different between endometrioid and non-endometrioid tumours (p=0.016 and p=0.048). For the endometrioid carcinomas, ADCmean and ADCmin were significantly different between low-grade (G1 and G2) and high-grade (G3) tumours (ADCmean/ADCmin = 0.75/0.65 vs. 0.59/0.49 x10-3 mm2/s, p=0.010 and p=0.013). Myometrial invasion, lymphovascular invasion, cervical involvement, lower uterine involvement, serosal involvement and lymph node metastasis were not significantly associated with ADC values.ADC measurements were useful for differentiating endometrioid and non-endometrioid carcinomas. High-grade endometrioid carcinomas had significantly lower ADC values compared to low-grade ones. Key Words: Endometrial cancer, Diffusion-weighted MRI, Apparent diffusion coefficient, Prognostic factors, Histological grade.

Minimally invasive approach in endometrial cancer with lower uterine segment involvement in stage ≥ II: A retrospective study

ObjectiveTo compare oncological outcomes in women with lower uterine segment involvement (LUSI) in endometrial carcinoma (EC) stage ≥ II - staged by a minimally invasive surgery (MIS) versus laparotomy. Study designA retrospective multi-center cohort study. Univariate analysis, Kaplan-Meier survival and Cox proportional hazard analysis were performed to compare between women staged by MIS and those staged by laparotomy. ResultsOver a median follow-up period of 3 years (interquartile range, 1.5–6 years) 212 women were included, 68 (32.1%) were surgically staged by MIS. Stages of disease did not vary between MIS and laparotomy and were 32.1%, 51.9%, and 16.0%, in stages II, III and IV – respectively. Adjuvant radiation and chemotherapy rate did not differ between groups. Overall recurrence rate was comparable (p = 0.084). Locoregional recurrence rate was higher in the MIS group odds ratio 2.17, 95% confidence interval 1.19–4.20).Overall and progression free survival were similar in both groups (log rank test p = 0.08 and p = 0.912 respectively). In Cox regression model adjusting for age, comorbidities, tumor grade, stage and adjuvant therapy, route of surgery (MIS vs. laparotomy) was not associated with overall survival (p = 0.169). ConclusionsIn women with advanced EC and LUSI, although MIS is associated with locoregional recurrences, survival is comparable to laparotomy.

Endometrial cancer in Lynch syndrome.

Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline pathogenic variants (PVs) in mismatch repair (MMR) genes. LS-associated endometrial cancer (LS-EC) is the most common extraintestinal sentinel cancer caused by germline PVs in MMR genes, including MLH1, MSH2, MSH6 and PMS2. The clinicopathologic features of LS-EC include early age of onset, lower body mass index (BMI), endometrioid carcinoma and lower uterine segment involvement. There has been significant progress in screening, diagnosis, surveillance, prevention and treatment of LS-EC. Many studies support universal screening for LS among patients with EC. Screening mainly involves a combination of traditional clinical criteria and molecular techniques, including MMR-immunohistochemistry (MMR-IHC), microsatellite instability (MSI) testing, MLH1 promoter methylation testing and gene sequencing. The effectiveness of endometrial biopsy and transvaginal ultrasound (TVS) for clinical monitoring of asymptomatic women with LS are uncertain yet. Preventive strategies include hysterectomy and bilateral salpingo-oophorectomy (BSO) as well as chemoprophylaxis using exogenous progestin or aspirin. Recent research has revealed the benefits of immunotherapy for LS-EC. The NCCN guidelines recommend pembrolizumab and nivolumab for treating patients with advanced or recurrent microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) EC.

Grossly unremarkable cervix in endometrial carcinomas: lymphovascular space invasion and microcystic elongated and fragmented pattern may be associated with high incidence of cervical stromal involvement

Accurate staging of endometrial carcinoma is crucial to optimize patients' care. A pivotal parameter that pathologists evaluate to guide staging is the presence of cervical stromal involvement. However, the standard protocol for adequate sampling of the cervix is lacking. A total of 71 grossly unremarkable cervices in hysterectomy specimens with endometrial carcinomas have been studied. Sixty-three (89.7%), five (7.0%), and three (4.2%) were FIGO stage I, II, and III, respectively. Of 71 (8.5%) cases, 6 cases had cervical stromal involvement, among which, 4 (67%) showed endometrioid carcinoma (EC), 1 case of serous carcinoma, and 1 carcinosarcoma. Microcystic elongated and fragmented (MELF) pattern was identified in 12 (16.9%) cases, among which 11 were EC. The presence of MELF pattern was associated with advanced age, deeper myometrial invasion, and advanced FIGO stage. Tumors with lower uterine segment involvement (5/6; 80%), lymphovascular space invasion (4/6; 67%), and MELF pattern (3/6; 50.0%) tended to have cervical stromal involvement. Thus, we provide evidence that the presence of these features in hysterectomy specimens from patients with endometrial carcinoma may warrant extended sampling of the cervix while submitting four representative sections (one section from each quadrant) seems adequate to evaluate for occult cervical stromal involvement in grossly unremarkable cervices in the absence of these features.

The utility of evaluating mismatch repair proteins in endometrial carcinoma: an experience from a tertiary referral centre in North India.

SummaryBackgroundEndometrial cancer (EC) is a common gynecological malignancy. Around 25-30% patients have mismatch repair deficiency (MMRd). Lynch syndrome is caused by germline mutations in MMR genes. Lynch-associated tumours have better prognosis, however implications for prognosis and survival is less known. Microsatellite insufficiency (MSI) is associated with high neoantigen loads and number of tumor infiltrating lymphocytes, which overexpresses PD-1 and PD-L1 and are excellent candidates for PD-1-targeted immunotherapies. In this study, we aim to evaluate the utility of MMR in patients with EC and its clinico-pathological correlation.MethodsEighty-two cases of EC which underwent MMR evaluation over a period of five years at our centre were included. Demographics, clinical details including family history, histopathological and immunohistochemical (IHC) parameters were recorded. Tumors with loss-of at least one protein were considered MMR deficient (MMRd) and those with intact expression were MMR proficient (MMRp).ResultsOf 82 cases tested, 27 (33%) were MMRd. Frequencies of IHC MMR loss of expression were: MLH1/PMS2: 17 (21%), MSH6 loss only: 3 (4%), MSH2/MSH6 loss: 3 (4%), PMS2 loss: 2 (2%). In MMRd cases, most common histologic tumor type was endometrioid adenocarcinoma (70%). Loss of expression was significantly (p < 0.001) more frequent in lower uterine segment involvement and positive family history.ConclusionsMSI plays an important role in the progression of endometrial cancer. Lower uterine segment involvement and positive family history are significant predictor of MMR loss. Routine testing of MMR proteins in endometrial cancer can contribute to screening of Lynch syndrome families and make immunotherapy available as a treatment option.

Lymphovascular space invasion in endometrial carcinoma: Tumor size and location matter

ObjectiveTo analyze histological factors possibly associated with lymphovascular space invasion (LVSI) and to determine which of those can act as independent surrogate markers. MethodsRetrospective cohort study performed between January 2001 and December 2014. LVSI was defined as the presence of tumor cells inside a space completely surrounded by endothelial cells. Risk factors evaluated included myometrial invasion, tumor grade, size, location, and cervical invasion. Univariate logistical regression models were applied to study any possible association of LVSI with these factors. Values were adjusted by multivariate logistic regression analysis. ResultsA total of 327 patients with endometrial carcinoma treated in our Centre were included. LVSI was observed in 120 patients (36.7%). Lower uterine segment involvement (OR 5.21, 95% CI:2.6–10.4, p < 0.001) and size ≥2 cm (OR 2.62, 95% CI: 1.14–6.1, p < 0.001) were independent factors for LSVI in multivariate analysis. In univariate analysis, LVSI was a surrogate marker in type 1 tumors with deep myometrial invasion (IB, 51.9% vs. IA, 16.0%; p < 0.001), grade 3 (G3 55.8% vs. G1 16.2%; p < 0.001), size ≥2 cm (37.9% vs. 16.1%, p = 0.005), those with involving the lower segment of the uterus (58.9% vs. 22.5%, p < 0.001) and/or with cervical stromal invasion (65.4% vs. 26.1%, p < 0.001), and in type 2 tumors (61.5% vs. 30.5%, p < 0.001). The use of uterine manipulator did not increase the rate of LVSI (35.5% vs. 40.5%, p = 0.612) as compared to no manipulator use. ConclusionsSize ≥2 cm and involvement of the lower uterine segment are independent factors for LSVI, in type 1 tumors, which can be used for surgical planning. LVSI is also more common in type 1 tumors with deep myometrial invasion, grade 3 and/or cervical stromal invasion, and also in type 2 tumors. The use of a uterine manipulator does not increase LVSI.

The impact of Ki-67 index, squamous differentiation, and several clinicopathologic parameters on the recurrence of low and intermediate-risk endometrial cancer.

Endometrial endometrioid carcinoma (EEC) represents approximately 75-80% of endometrial carcinoma cases. Three hundred and thirty-six patients with EEC followed-up in the authors’ medical center between 2010 and 2018 were included in our study. Two hundred and seventy-two low and intermediate EEC patients were identified using the European Society for Medical Oncology criteria and confirmed by histopathological examination. Recurrence was reported in 17 of these patients. The study group consisted of patients with relapse. A control group of 51 patients was formed at a ratio of 3:1 according to age, stage, and grade, similar to that in the study group. Of the 17 patients with recurrent disease, 13 patients (76.5%) were Stage 1A, and 4 patients (23.5%) were Stage 1B. No significant difference was found in age, stage, and grade between the case and control groups (p > 0.05). Body mass index, parity, tumor size, lower uterine segment involvement, squamous differentiation (SqD), and Ki-67 index with p<0.25 in the univariate logistic regression analysis were included in the multivariate analysis. Ki-67 was statistically significant in multivariate analysis (p = 0.018); however, there was no statistical significance in SqD and other parameters. Our data suggest that the Ki-67 index rather than SqD needs to be assessed for recurrence in patients with low- and intermediate-risk EEC.

The uterine pathological features associated with sentinel lymph node metastasis in endometrial carcinomas.

BackgroundIn recent years, sentinel lymph node excision and ultrastaging have been performed in endometrial carcinomas to obtain information about lymph node status, avoiding unnecessary complete pelvic and paraaortic lymphadenectomy. The purpose of this retrospective study was to provide a comprehensive evaluation of the pathological features of endometrial carcinomas and their significance in association with sentinel lymph node involvement.MethodsPatients with endometrial carcinomas, preceded by sentinel lymph node mapping, were classified into Group-I and Group-II with negative and positive involvement, respectively. The pathological features, associated with sentinel lymph node involvement, were statistically analyzed, including determination of test performance parameters.ResultsAmong 70 patients who had undergone hysterectomy and sentinel lymph node excision, 61 had carcinoma and 9 had atypical hyperplasia. There were 50 patients in Group-I and 10 in Group-II. In Group-II, the significant pathological features were: 1) lower uterine segment involvement (100%), 2) an average tumor size of ≥5 CM, 3) lymphovascular invasion (50%), 4) cervical stromal invasion (40%), and 5) depth of myometrial invasion of ≥50% (50%). The incidences of these pathological features were significantly less in Group-I. Statistical analyses singled out “lower uterine segment involvement” as the most important feature.ConclusionsWe have identified five pathological features which are associated with sentinel lymph node involvement. Since lower uterine segment involvement has occurred in all cases of the Group-II cohort, we recommend FIGO and other organizations that determine staging rules should consider whether tumors that involve the lower uterine segment should be staged as higher than “1a”, if the findings in this small series are confirmed by other studies. The results of this study may guide pathologists and oncologists in the diagnostic and therapeutic approaches to management of endometrial carcinomas.

Concurrently Presenting Endometrial And Ovarian Endometrioid Adenocarcinomas- A Clinicopathologic Study Of 52 Cases

Abstract Introduction/Objective Concurrent presentation of endometrioid adenocarcinomas in endometrium and ovary is uncommon, but oft-noted. They may arise from ovarian metastasis of endometrial carcinoma, endometrial metastasis of ovarian carcinoma, or synchronous development of independent primary lesions. Scully and Young criteria have been widely used to differentiate the site of origin.1 Role of a field effect in the genesis of synchronous carcinomas is supported by increasing evidence that endometrioid ovarian carcinomas arise from endometriosis. 2–5 Methods All cases of concurrent endometrioid adenocarcinomas of the endometrium and ovary between 2002 and 2019 in the Mount Sinai health system New York were included, using pathology database (Powerpath) and EMR database (Epic). Results 52 cases of concurrent endometrioid adenocarcinomas of endometrium and ovary were identified between 2002 and 2019. Mean age at presentation was 54.07 years (24–80). 69.2% had synchronous origin, 21.15% had endometrial primary and 3.8% had an ovarian primary. Ovarian endometriosis was identified in 51.9% and complex atypical hyperplasia in 26.9%. Lower uterine segment involvement was seen in 26.9%, bilateral ovarian involvement in 40.3%, fallopian tube involvement in 23% and lymphovascular space invasion in 25%. Different histologic grade of ovarian and endometrial counterparts was noted in 25% cases. Synchronous endometrioid carcinomas had the following characteristics: mean age at presentation 50.6 years, associated with CAH in 33.3% and endometriosis in 66.6%, presentation at stage 1 in 63.8% and lower grade of differentiation (grade 1/2) in 80.5% cases. Conclusion In majority of cases, synchronous endometrioid carcinomas have a younger mean age at presentation, are lower grade tumors, present at stage 1 and have associated endometriosis. It can be inferred that the percentage of synchronous tumors with endometriotic foci would be even higher (with extensive sampling &amp; assuming that the neoplastic process has replaced native benign endometriotic foci) – pointing towards the likely role of endometriosis in the genesis of these tumors.

Endometrial cancer in young women: prognostic factors and treatment outcomes in women aged ≤40 years

ObjectiveEndometrial cancer in pre-menopausal patients aged ≤40 years is rare and poses both diagnostic and management challenges. The goal of this study was to investigate the clinical and pathologic factors...

Outcomes and relapse patterns of stage IB grade 2 or 3 endometrial cancer treated with adjuvant vaginal brachytherapy

IntroductionRisk factors for pelvic recurrence in early stage endometrial cancer are poorly understood. We sought to describe outcomes, patterns of failure, and risk factors for recurrence among patients with grade...

Comparison of Adjuvant Radiation Treatment and Chemotherapy Sequencing in Women with Advanced Stage Endometrial Carcinoma

There remains no definitive consensus on the optimal sequencing of adjuvant chemotherapy (CT) and radiotherapy (RT) for women with stage III endometrial carcinoma. Recurrence-free (RFS), disease-specific (DSS) and overall survival (OS) endpoints were compared between women who received RT concurrent with cisplatin followed by 4 more cycles of CT (carboplatin and paclitaxel) and those who received 3 cycles of CT (carboplatin and paclitaxel) then RT alone then 3 more cycles of CT (“sandwich” technique). After IRB approval, we analyzed the data of 140 women with FIGO stage III disease treated from 1/1995 to 12/2017 at our institution. All women were surgically staged and received adjuvant combined modality therapy with different sequences (concurrent or “sandwich”). Differences in variables between the two arms were assessed by chi-squared test. Survival endpoints were assessed by Kaplan-Meier and log-rank tests. Univariate (UVA) and multivariate (MVA) models with Cox regression analyses were generated to determine significant predictors for survival endpoints. Of the 140 women included, 66 (47%) received the “sandwich” technique and 74 (53%) received concurrent therapy. Median follow-up was 43.7 months. There were 77 women (55%) with uterine endometrioid carcinoma and 111 women (80%) with stage IIIC disease. The concurrent group was found to have a significantly better 5-year RFS rate (Hazard Ratio [HR]=0.70, 95% Confidence Interval [CI] 0.46-0.85) compared to the sandwich technique (HR 0.47 [0.33-0.6], p=0.02). There was no statistically significant difference in the pattern of recurrence between the two groups. On MVA, significant predictors of worsened RFS were higher comorbidity burden (Charlson score)(p=0.02), grade 3 vs 2 (p=0.01), FIGO stage IIIC disease (p=0.04), and lower uterine segment involvement (p=0.001). There was no statistically significant difference found between the two groups in regards to OS and DSS. This study suggests that the sequence of radiation therapy given concurrently with chemotherapy is relatively better in terms of recurrence-free survival in women with stage III endometrial carcinoma compared to the “sandwich” approach. These data warrant further validation in a multi-institutional prospective study.

Lower uterine segment involvement in lymphovascular space invasion and lymph node metastasis in endometrioid endometrial cancer.

To evaluate the correlation between lymphovascular space invasion (LVSI) indicating lower uterine segment involvement (LUSI) in endometrioid endometrial cancer and lymph node metastasis based on the lymphatic drainage difference between the uterine corpus and the lower segment. Patients who underwent staging surgery for endometrioid endometrial cancer between January 2010 and January 2019 at our institution were reviewed. The clinicopathologic findings and LUSI status of the patients were compared with their LVSI and lymph node metastasis status. Of the 253 patients included in this study, 49 (19.4%) had LUSI. Among these patients, none of the 31 LVSI-negative patients had metastatic lymph node involvement. However, of the 18 LVSI-positive patients, half had metastatic lymph node involvement; this difference was significant (p < 0.05). The significant correlation between LVSI and lymph node metastasis in LUSI-positive cases indicates that pathologists should also focus on LVSI findings in the frozen examination required for the decision of staging surgery in patients with endometrioid endometrial cancer limited to the uterus. This is especially important in patients with a lower uterine segment involvement.

The incidence of microscopic adnexal metastatic disease in women with presumed early stage endometrial cancer.

e17128 Background: The standard surgical staging for endometrial cancer has been established as a total laparoscopic hysterectomy,bilateral salpingo-oopherectomy and lymphadenectomies. However, ovarian removal can have significant consequences in pre- and peri-menopausal women, which comprise 25% newly diagnosed endometrial cancer. The potential ramifications of premature surgical menopause are clinically important. The goal of this study is to determine the incidence of microscopic adnexal metastatic disease in younger patients with presumed early stage endometrial cancer. Methods: From January 2005 through December 2010, 57 women who were 52 years old or younger with presumed early stage endometrial cancer were identified from our institutional database. Inclusion criteria included (1) FIGO grade 1 endometrioid endometrial cancer on endometrial biopsy, or (2) FIGO grade 1 endometrioid endometrial cancer on frozen section specimen with &lt; 50% myometrial invasion, no evidence of metastatic disease on pre-operative imaging, and no grossly visible metastatic disease in the peritoneal cavity during the staging surgery. Results: Of these 57 patients, four (7%) had lymphovascular space invasion, 20 (35%) had lower uterine segment involvement, 26 (45%) had superficial myometrial invasion or no residual carcinoma, while three (5%) unexpectedly had 50% or greater myometrial invasion on final pathology. Half of our patient population (50%) received vaginal brachytherapy. Of the 57 patients, one (1.8%) had microscopic adnexal involvement in a fallopian tube which upstaged her to stage IIIA disease. Pathological risk factors for advanced stage included LVI, lower uterine segment disease, and 50% myometrial invasion. Conclusions: After a thorough pre-operative evaluation and intra-operative exploration, preservation of the ovaries appears to be a safe and viable option for younger women who are diagnosed with presumed early stage disease. We suggest that ovarian preservation should be discussed on an individual basis in pre- peri-menopausal patients who meet the above-mentioned strict eligibility criteria.

Management of Stage IB Grade III Endometrial Cancer: Single Institute Experience

Background and Objective: There is marked controversy regarding optimal management patients with stage IB grade III endometrial carcinoma. The present study analyzes the current practices regarding adjuvant radiation therapy for those patients in our institute and also assessed prognostic factor affecting overall survival outcome. Patients and Methods: A total 66 patients with postoperative FIGO stage 1B, grade III endometrial carcinoma were treated and evaluated between the years 2009 and 2014. Risk factors assessed age (4 cm), site of primary tumor (involvement of lower uterine segment versus no involvement), Lymphadenectomy (performed versus not performed), Lymph-vascular space invasion (positive or negative), type of surgery performed (less than total abdominal hysterectomy and bilateral salpingo-ophorectomy (TH/BSO) versus greater than or equal TH/BSO), radiation sequence with surgery (no radiation versus adjuvant radiation), and type of radiation (pelvic external beam radiotherapy versus vaginal brachytherapy versus both). Results: Adjuvant radiation therapy after surgery was associated with significantly better time to relapse (p = 0.001) in comparison to those patients who underwent surgery alone. There was statistically significant improvement of survival of patients who received adjuvant radiation therapy in comparison with those who underwent surgery alone. There was no statistically significant difference in relapse between external pelvic radiotherapy, brachytherapy and both (p = 0.161). There was no statistically significant difference in overall survival between different types of adjuvant radiation therapy (p = 0.318). Adjuvant radiation therapy (HR 0.173, 95% CI 0.049 - 0.609, p = 0.006) and tumor size (HR 4.065, 95% CI 1.120 - 14.761, p = 0.033) were the only statistically significant predictors for relapse in multivariate analysis. Adjuvant radiation therapy (HR 0.159, 95% CI 0.045 - 0.563, p = 0.004), age (HR 10.357, 95% CI 1.195 - 89.746, p = 0.034) and lymphadenectomy (HR 0.240, 95% CI 0.071 - 0.811, p = 0.022) were statistically significant predictors for overall survival. Conclusion: The current study suggested that adjuvant radiation therapy definitely improve survival of patients with stage IB, grade III endometrial cancer. There is a need for more randomized trials to define patients who require adjuvant radiation therapy and define what type of radiation should be received. Well defined guidelines are very important to standardize treatment and cut costs in clinical practice.

Predictors of Pelvic Recurrence in Stage IB Grade 2-3 Endometrioid Endometrial Adenocarcinoma Treated with Post-Operative Vaginal Brachytherapy

Optimal adjuvant management of surgically staged FIGO stage IB grade 2 (G2) and grade 3 (G3) endometrial endometrioid adenocarcinoma (EAC) is controversial. The objective of this study is to report outcomes utilizing adjuvant vaginal brachytherapy (VB) without pelvic radiotherapy (RT) for patients with surgically staged IB G2 and G3 EAC and to analyze rates and predictors of pelvic recurrence. Retrospective review of an institutional database identified patients diagnosed between 2005-2015 with 2009 FIGO stage IB G2 and G3 EAC. All patients underwent comprehensive surgical staging and VB as the sole adjuvant RT as per institutional guidelines during the study period. Disease free survival (DFS) was calculated from the date of primary surgery to date of last follow up or recurrence, and a minimum of 6 months follow-up was required for inclusion. Kaplan-Meier methods were used to estimate DFS. Pearson chi-squared test was used to determine association of pathologic variables and pelvic recurrence. A total of 78 patients were identified for inclusion. The median age at diagnosis was 67 (range, 42-93). Surgical staging included hysterectomy, bilateral salpingo-oopherectomy, pelvic washings, pelvic lymph node dissection (98.7%), and paraaortic node sampling (78.2%). Fifty-five patients (71%) had G2 EAC and 23 (29%) had G3 EAC. Lymphovascular invasion (LVI) was observed in 37 (47%), lower uterine segment involvement (LUSI) in 38 (49%), and outer 1/3rd myometrial invasion (MMI) (defined as ≥ 67% MMI) in 39 (50%). Median number of pelvic lymph nodes removed was 18. The majority (88.5%) received VB alone and 11.5% received VB in combination with chemotherapy. Median follow up was 45.5 months (range 6.3-151.8) and 3-year estimated DFS was 84.7% for the entire cohort. There were a total of 11 recurrences, of which 3 (27.3%) were distant only. The remainder (72.3%) had a pelvic component including 5 which were pelvic and distant and 3 which were isolated to the pelvis. Median time to recurrence was 27.8 months (range, 11.5 - 46.9). On univariate analysis, G3 versus G2 (p = 0.600), LVI present versus absent (p = 0.388), and ≥20 versus <20 pelvic nodes dissected (p = 0.051) were not associated with higher pelvic recurrence risk. Presence of LUSI (p = 0.03) and outer 1/3rd MMI (p = 0.03) were associated with increased risk of pelvic failure. Stage IB G2 and G3 patients treated with adjuvant VB following surgical staging overall fared well, and isolated pelvic recurrences were few in number. While grade and LVI were not associated with increased pelvic failure in this cohort, the association of LUSI and outer 1/3rd MMI is intriguing. Further investigation into risk factors for pelvic recurrence in stage I EAC would be valuable to identify subgroups which benefit the most from pelvic RT.