High-risk Early-stage Endometrial Cancer Research Articles

Clinical characteristics and radiation therapy modality of younger patients with early-stage endometrial cancer, a multicenter study in China’s real world

BackgroundEndometrial cancer is a prevalent gynecologic malignancy found in postmenopausal women. However, in the last two decades, the incidence of early-stage has doubled in women under 40 years old. This study aimed to investigate the clinical and pathological characteristics and adjuvant therapeutic modalities of both young and not -young patients with early-stage endometrial cancer in China’s real world.MethodsThis retrospective study analyzed patients with early-stage endometrial cancer at 13 medical institutions in China from 1999 to 2015. The patients were divided into two groups: young (≤ 45 years old) and non-young (> 45 years old). Statistical comparisons were conducted between the two groups for clinical characteristics, pathological features, and survival. The study also identified factors that affect local recurrence-free survival (LRFS) using Cox proportional risk regression analysis. Propensity score matching (1:1) was used to compare the effects of local control between vaginal brachytherapy (VBT) alone and pelvic external beam radiotherapy (EBRT) ± VBT.ResultsThe study involved 1,280 patients, 150 of whom were 45 years old or younger. The young group exhibited a significantly higher proportion of stage II, low-risk, lower uterine segment infiltration (LUSI), and cervical invasion compared to the non-young group. Additionally, the young patients had significantly larger maximum tumor diameters. The young group also had a significantly higher five-year overall survival (OS) and a five-year LRFS. Age is an independent risk factor for LRFS. There was no significant difference in LRFS between young patients with intermediate- to high-risk early-stage endometrial cancer who received EBRT ± VBT and those who received VBT alone.ConclusionsIn the present study, young patients had better characteristics than the non-young group, while they exhibited higher levels of aggressiveness in certain aspects. The LRFS and OS outcomes were better in young patients. Age is an independent risk factor for LRFS. Additionally, VBT alone may be a suitable option for patients under 45 years of age with intermediate- to high-risk early-stage endometrial cancer, as it reduces the risk of toxic reactions and future second cancers while maintaining similar local control as EBRT.

Impact of sentinel lymph node mapping on survival in patients with high-risk endometrial cancer in the early stage: A matched cohort study.

The aim of this study was to compare patient survival using sentinel lymph node (SLN) procedure and pelvic lymphadenectomy for stating early-stage high risk endometrial cancer. Patients who underwent surgery for early-stage high risk endometrial cancer between 2010 and 2017 were extracted from the incidence registry of the SEER program. We identified patients who underwent SLN mapping. Patients who initially underwent pelvic lymphadenectomy were selected as the comparison group. One-to-one matching was performed according to age, ethnicity, histology, extension and grade. The primary outcome was disease-specific survival. The secondary outcome was overall survival. A total of 326 patients who underwent SLN mapping and 326 who underwent pelvic lymphadenectomy initially were included in the study. The three-year analysis did not find a significant difference between the SLN and lymphadenectomy groups on disease-specific survival probability (88.2% vs 82.7, P = 0.07) and on overall survival probability (82.7% vs 78.2%, P = 0.57). Patients who underwent SLN mapping had a lower mean number of lymph nodes removed (mean 3 vs 16, P < 0.001) and there was a higher rate of patients with positive pelvic lymph nodes (18% vs 14%, P = 0.04). Following adjustment for confounding factors, disease-specific survival did not vary according to the lymph node intervention performed (P = 0.056), but the SLN group had better overall survival than those in the lymphadenectomy group (P = 0.047). The SLN technique was not associated with poorer disease-specific survival than pelvic lymphadenectomy even after adjustment. These results suggest that SLN is an acceptable and safe procedure in surgical staging for early-stage high-risk endometrial cancer.

Efficacy and prognosis of adjuvant treatment of endometrial cancer with medroxyprogesterone acetate COX regression analysis.

Endometrial cancer is one of the most commonly diagnosed gynecological cancers worldwide, and early-stage high-risk endometrial cancer has a poor prognosis. Adjuvant treatments after surgery, such as chemotherapy and radiotherapy, have been widely used in clinical practice to improve patient survival. Medroxyprogesterone acetate is a synthetic progestogen that has been reported to have potential anticancer effects in endometrial cancer. However, its efficacy, safety, and long-term prognostic benefits as an adjuvant treatment for endometrial cancer remain controversial. Therefore, this study aimed to observe the efficacy and prognostic impact of adjuvant medroxyprogesterone acetate treatment in patients with early-stage high-risk endometrial cancer and evaluate its safety. To observe the efficacy and prognosis of adjuvant treatment of endometrial cancer with medroxyprogesterone acetate and to evaluate its safety. We collected the clinical data of 200 patients with early-stage high-risk endometrial cancer who were admitted to the Department of Obstetrics and Gynecology of our hospital from January 2018 to December 2022. The control group (100 patients) underwent conventional surgical treatment, and the study group (100 patients) was administered adjuvant medroxyprogesterone acetate tablets on top of the control group. The Kaplan-Meier curve analysis and log-rank test were performed to determine the possible factors influencing the 5-year cumulative survival rate in the patients. The Cox regression analysis was performed to identify the factors influencing the survival prognosis of endometrial cancer. According to the Cox regression analysis, age [hazard ratio (HR) = 4.636, 95% confidence interval (95%CI): 1.411-15.237], pathological type (HR = 6.943, 95%CI: 2.299-20.977), molecular typing (HR = 5.789, 95%CI: 3.305-10.141), and myometrial infiltration (HR = 5.768, 95%CI: 1.898-17.520) were factors influencing the prognosis of patients with early-stage high-risk endometrial cancer. Age, pathological type, molecular typing, and myometrial infiltration were all relevant factors affecting the prognosis of early-stage high-risk endometrial cancer. The potential long-term prognostic benefit of adjuvant postoperative radiotherapy in patients with early-stage high-risk endometrial cancer is worthy of clinical consideration.

Role of systematic lymphadenectomy in patients with intermediate to high-risk early stage endometrial cancer.

To determine the clinical significance of systematic lymph node dissection (LND) and to better define the relevant extent of LND in intermediate- to high-risk early stage endometrial cancer (EC). Patients who received surgery as a primary treatment of histologically confirmed EC and preoperatively considered as uterus-confined early stage disease were included in the study population. The rates of lymph node metastasis (LNM) according to the risk groups and anatomic sites were assessed. Univariate and multivariate analyses were performed to evaluate risk factors for recurrence. A total of 804 patients were included in the study analysis. The rates of LNM were significantly different according to the risk group; 1.2% in low-risk, 20.1% in intermediate-risk, and 30.0% in high-risk group. When assessing the rates of LNM in individual anatomic sites, positive LNs were evenly distributed throughout the pelvic and para-aortic regions. In the intermediate to high-risk EC cases, the rates of para-aortic LNM below and above inferior mesenteric artery (IMA) were 11.1% and 12.5%, respectively. On multivariate analysis, LNM was the only independent risk factor for recurrence in the intermediate to high-risk EC (hazard ratio=2.63, 95% confidence interval=1.01-6.82, p=0.047). LNM was frequently observed in intermediate- and high-risk early stage EC and it served as an independent risk factor for recurrence. When considering the similar rates of LNM between below and above IMA, nodal assessment needs to be performed up to the infra-renal level, especially for the staging purpose in high-risk EC.

Lymphadenectomy, sentinel node mapping plus backup lymphadenectomy and sentinel node mapping alone in low-, intermediate, and high-risk endometrial cancer (555)

<b>Objectives:</b> Sentinel node mapping (SNM) has replaced lymphadenectomy for staging surgery in apparent early-stage endometrial cancer (EC). Here, we evaluate the long-term survival of the three different approaches of nodal assessment in low, intermediate, and high-risk EC. <b>Methods:</b> This is a multi-institutional retrospective study evaluating long-term outcomes (at least three years of follow-up) of EC patients having nodal assessment between 2006 and 2016. In order to reduce possible confounding factors, we applied a propensity-matched algorithm. <b>Results:</b> Charts of 940 patients were evaluated, with 174 (18.5%), 187 (19.9%), and 579 (61.6%) having SNM, SNM followed by backup lym- phadenectomy and lymphadenectomy, respectively. Applying a propensity score matching algorithm (1:1:2), we selected 500 patients: 125 SNM versus 125 SNM plus backup lymphadenectomy versus 250 lymphadenectomies. Baseline characteristics of the study population were similar between groups. The prevalence of nodal disease was 14%, 16%, and 12% in patients having SNM, SNM followed by backup lymphadenectomy and lymphadenectomy, respectively. Overall, 19 (7.6%) patients were diagnosed with low volume nodal disease (seven and 12 patients with micrometastasis and isolated tumor cells). The mean (SD) follow-up time was 62 (±11) months. The survival analysis comparing the three techniques did not show statistical differences in terms of disease-free (p=0.750) and overall survival (p=0.899). Similarly, the type of nodal assessment did not impact survival outcomes after stratification on the basis of uterine risk factors. <b>Conclusions:</b> Our study highlighted that SNM provides similar longterm oncologic outcomes to lymphadenectomy. Further evidence is warranted to assess the prognostic value of low volume disease detected by ultrastaging and the role of molecular/genomic profiling.

Cost-Effectiveness Analysis of Tumor Molecular Classification in High-Risk Early-Stage Endometrial Cancer

(Abstracted from Gynecol Oncol 2022;164:129–135) Endometrial cancer (EC) remains the most common gynecologic cancer in the United States, accounting for nearly 13,000 deaths in 2020 alone. Surgery remains the mainstay of treatment for early-stage EC; however, adjuvant treatment is often indicated.

Cost-effectiveness analysis of tumor molecular classification in high-risk early-stage endometrial cancer

PurposeTumor molecular analyses in endometrial cancer (EC) includes 4 distinct subtypes: (1) POLE-mutated, (2) mismatch repair protein (MMR) deficient, (3) p53 mutant, and (4) no specific molecular profile. Recently, a sub-analysis of PORTEC-3 demonstrated notable differences in treatment response between molecular classification (MC) groups. Cost of testing is one barrier to widespread adoption of MC. Therefore, we sought to determine the cost-effectiveness of MC in patients with stage I and II high-risk EC. MethodsA Markov decision model was developed to compare tumor molecular classification (TMC) vs. no testing (NT). A healthcare payor's perspective and 5-year time horizon were used. Base case data were abstracted from PORTEC-3 and the molecular sub-analysis. Cost and utility data were derived from public databases, peer-reviewed literature, and expert input. Strategies were compared using the incremental cost-effectiveness ratio (ICER) with effectiveness in quality-adjusted life years (QALYs) and evaluated with a willingness-to-pay threshold of $100,000 per QALY gained. Sensitivity analyses were performed to test model robustness. ResultsWhen compared to NT, TMC was cost effective with an ICER of $25,578 per QALY gained; incremental cost was $1780 and incremental effectiveness was 0.070 QALYs. In one-way sensitivity analyses, results were most sensitive to the cost of POLE testing, but TMC remained cost-effective over all parameter ranges. ConclusionsTMC in early-stage high-risk EC is cost-effective, and the model results were robust over a range of parameters. Given that MC can be used to guide adjuvant treatment decisions, these findings support adoption of TMC into routine practice.

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.

800P Tailoring adjuvant treatments in high-risk early stage endometrial cancer: Clinical outcomes of sequential chemoradiation in a real-word scenario

Chemotherapy plus external beam radiotherapy (EBRT) is the current standard adjuvant therapy for patients (pts) with high-risk stage I-III endometrial cancer (EC). Despite this, the best combination schedule for chemoradiation (CR) has not been defined yet. We aimed at describing the clinical outcomes of pts with EC receiving platinum-based chemotherapy administered 2-3 cycles before and after radiotherapy as adjuvant treatment (‘sandwich’ chemoradiation, SCR).

Defining optimal adjuvant treatment for high-risk early-stage endometrial cancer

<h3>Objectives:</h3> There is a paucity of data to determine the optimal adjuvant treatment of early-stage, high-risk endometrial histologies. While many retrospective series focus on uterine serous cancer, the optimal treament for other high risk subtypes, including G3 endometrioid cancer, clear cell carcinoma or carcinosarcoma is not yet clear. We sought to determine patterns and outcomes of adjuvant treatment for early-stage high-risk endometrial cancers of multiple histologic subtypes. <h3>Methods:</h3> After Institutional Review Board approval, a retrospective review of patients at Montefiore Medical Center diagnosed with early stage high-risk endometrial cancer between 2006 and 2018 was conducted. Inclusion criteria included: 1) Stage I-II disease 2) Grade 3 endometrioid, carcinosarcoma, clear cell, serous, or mixed histologies. Demographic and clinical information pertaining to cancer treatment was collected. The primary outcome was recurrence-free survival. Univariate and multivariate analyses were performed and a Kaplan-Meier progression free survival curve was created using STATA 14.2. P-value <0.05 was considered statistically significant. <h3>Results:</h3> A total of 1208 patients with endometrial cancer were identified, 249 of which met inclusion criteria. Sixty-percent (149) of patients had serous, clear cell, or mixed histologies, 17% (43) had carcinosarcoma, 23% (57) had Grade 3 endometrioid histology. Most patients received adjuvant combination chemoradiotherapy (52%, N=131) whereas 20% (49) received radiation alone (brachytherapy or external beam), 7% (18) received chemotherapy alone, and 20% (50) received no adjuvant treatment. Of the 48 (19%) disease recurrences, 25 (45%) were distant metastases at the time of recurrence. Combined chemoradiotherapy was associated with increased recurrence-free survival compared with chemotherapy alone (p=0.026) or radiation alone (p=0.004). Compared to G3 endometrioid histology, the hazard ratios for recurrence were: 3.70 (CI 1.31-10.41, p=0.01) for serous histology, 1.37 (CI 0.15-12.21, p=0.78) for clear cell, 9.70 (CI 3.22-29.16, p<0.01) for carcinosarcoma, and 4.59 (CI 1.28-16.46, p=0.02) for mixed histology. Charlson Cormorbidity Index was also associated with cancer recurrence (HR 1.53, CI 1.28-1.82, p<0.01), as was age (HR 0.95, CI 0.92-0.99, p=0.01). <h3>Conclusions:</h3> Multimodal treatment with chemotherapy and radiation therapy is associated with increased recurrence free survival in patients with high-risk early-stage endometrial cancers, in comparison to radiation or chemotherapy alone after surgical staging. Histologic subtype, comorbid conditions, and age all significantly impact survival. Notably, recurrence in clear cell tumors were not significantly impacted by adjuvant treatment with chemotherapy and radiation therapy. Randomized trials are needed to determine the optimal treatment of high-risk histologic subtypes.

Outcomes after chemotherapy, radiation or combination therapy for high-intermediate and high-risk early-stage endometrial cancer

Objective: The adjuvant therapy for high-intermediate and high-risk endometrial cancer remains controversial. A recent randomized trial (PORTEC-3) reported that survival was improved with combination chemotherapy and radiotherapy, although the survival benefit was most pronounced in women with stage III tumors. We analyzed the association between multimodal therapy and survival for women with stage I–II high- and high-intermediate risk endometrial cancer.

Off-study utilization of experimental therapies: Analysis of GOG249-eligible cohorts using real world data

ObjectiveAdjuvant management of women with high-intermediate- and high-risk early-stage endometrial cancer remains controversial. Recently published results of GOG 249 revealed that vaginal brachytherapy plus chemotherapy (VBT + CT) was not superior to whole pelvic radiation therapy (WPRT) and was associated with more toxicities and higher nodal recurrences. This study examined off-study utilization of VBT + CT among women who met criteria for GOG 249 in the period prior to study publication. MethodsWomen diagnosed with FIGO IA-IIB endometrioid, serous, or clear cell uterine cancer between 2004-2015 and treated with hysterectomy and radiotherapy (RT) were identified in the National Cancer Database. Cochrane-Armitrage trend test was used to assess trends over time. Univariate and multivariate Cox analyses were performed to calculate odds ratio (OR) of VBT + CT receipt and hazard ratio (HR) of OS. Propensity-score matched analysis was conducted to account for baseline differences. Results9956 women met inclusion criteria. 7548 women (75.8%) received WPRT while 2408 (24.2%) received VBT + CT in the study period. From 2004-2015, there was a significant increase in VBT + CT use (p < 0.001) with the largest overall increase occurring in 2009 to 22%. Factors significantly associated with VBT + CT receipt included higher socioeconomic status (p < 0.001), higher grade endometrioid cancer (p < 0.001), and aggressive histology (p < 0.001). After propensity-score matching, VBT + CT was associated with improved OS (HR 0.74, 95% CI 0.58–0.93); however, when stratified by FIGO stage, VBT + CT was only associated with improved OS for FIGO stage 1B (HR 0.62, 95% CI 0.44–0.87). ConclusionsThere was significant use of experimental arm off-study treatment in the United States prior to report of GOG 249 results. Providers should be cautious when offering off-study treatment utilizing an experimental regimen given uncertainty about efficacy and toxicity.

PET-CT scan in the preoperative workup of early stage intermediate- and high-risk endometrial cancer

Objectives: To evaluate positron emission tomography-computed tomography (PET-CT) for the preoperative management of early-stage intermediate- and high-risk endometrial cancer (EC).Study design: Data of patients with intermediate- and high-risk early-stage EC were retrieved from a prospectively collected database. Patients with preoperative PET-CT followed by surgical staging including pelvic lymphadenectomy were analyzed. Diagnostic performance for lymph node (LN) metastasis was evaluated.Results: Overall, 45 patients were included: 27 (60%) and 18 (40%) with intermediate- and high-risk EC, respectively. Four patients (8.8%) had LN metastasis, three correctly identified at PET-CT, yielding a sensitivity of 75% (95% CI 21.9–98.7). Among 41 patients (91.2%) without LN metastasis, 38 had negative PET-CT with specificity of 92.7% (95% CI 78.9–98.1). The negative predictive value (NPV) was 97.4% (95% CI 84.9–99.9) and the positive predictive value was 50% (95% CI 13.9–86.1).Conclusions: The utility of PET-CT is limited by the low sensitivity for LN metastasis in intermediate- and high-risk early-stage EC, that may impede to consider PET-CT alone an adequate alternative to surgical retroperitoneal staging by lymphadenectomy or sentinel LN biopsy. However, the high diagnostic accuracy, specificity and NPV might support its adoption to improve the diagnostic accuracy of the sentinel LN algorithm.

Patterns of Failures and Clinical Outcome of Patients with Early-Stage, High-Risk, Node-Negative Endometrial Cancer Treated with Surgery Followed by Adjuvant Platinum-Based Chemotherapy and Vaginal Brachytherapy

Objective: To assess the clinical outcome of patients with high-risk early-stage endometrial cancer and negative pelvic nodes who received adjuvant platinum-based chemotherapy plus vaginal brachytherapy (VBT). Methods: This investigation assessed 80 patients who underwent hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy for stage Ib-II, grade 2–3 endometrioid (n = 43) or stage Ia-II nonendometrioid (n = 37) endometrial cancer. Results: Five-year local control rate, 5-year disease-free survival, and 5-year overall survival were 97, 87, and 97%, respectively, for endometrioid carcinoma, and 66, 50, and 72%, respectively, for nonendometrioid carcinoma. Conclusions: This retrospective study appears to show that adjuvant platinum-based chemotherapy plus VBT achieve very good results in endometrioid carcinoma. This combined treatment seems to be less effective in nonendometrioid carcinoma.

Impact of adjuvant treatment on outcome in high-risk early-stage endometrial cancer: a retrospective three-center study.

High grade and non-endometrioid endometrial cancers carry a poor prognosis, and the lack of randomized prospective data has led to a wide range of practice regarding adjuvant therapy. The objective of this study was to evaluate the outcomes of different treatment strategies in patients with high-risk, early-stage endometrial cancer. Patients with high-grade endometrioid, serous endometrial cancer and carcinosarcoma diagnosed between 2000 and 2012 were identified from databases in three gynecologic oncology divisions, in Toronto and in Israel. Adjuvant treatment practices differed across the centers, creating a heterogeneous cohort. A comparison of stage I patients stratified by adjuvant treatment was undertaken. Log-rank tests and Cox proportional hazards models were employed to compare recurrence and survival across treatment groups. 490patients with high risk endometrial cancer were identified, among them 213 patients with stage I disease. Israeli patients received more chemotherapy (41% vs 10% in stage I disease; P<0.001) than patients in Toronto. Chemotherapy was not associated with improved disease-free, disease-specific or overall survival, nor was it associated with fewer distant recurrences (50% vs 54%). Radiation was also not associated with improved recurrence or survival, nor did it affect the pattern of recurrence. On Cox multivariable analysis, neither radiation treatment nor chemotherapy were significantly associated with outcome (HR for recurrence, 0.72 for pelvic radiation (P=0.46) and 1.99 for chemotherapy (P=0.09); HR for death, 0.67 for pelvic radiation (P=0.29) and 1.03 for chemotherapy (P=0.94)). In this retrospective analysis, neither adjuvant radiation nor chemotherapy were associated with improved outcome in stage I, high risk endometrial cancer.

Patterns of Care and Outcomes of Adjuvant Treatment in Stage II Endometrioid Carcinoma

GOG 249 reaffirmed adjuvant pelvic radiation as the standard of care for high-risk early stage endometrial cancer. Patients with Stage II disease, elderly patients, and patients with poor performance status were underrepresented in the trial population. We utilized the National Cancer Database to study the patterns of care in stage II patients stratified by adjuvant therapy (AT), age, and performance status. We included patients diagnosed in 2004-2014 with stage II (FIGO 2009) endometrioid carcinoma who underwent TAH/BSO with negative margins. Patients with unknown AT, refusing AT, who died after surgery, or who did not have AT because of comorbidity were excluded. All patients with PXRT received a minimum dose of 45Gy and all patients with chemotherapy had multiagent chemotherapy (mCT). Adjuvant therapies compared were surgery alone, mCT alone, VBT alone, PXRT alone, VBT+mCT, PXRT+VBT, PXRT+VBT+mCT. Multivariate Cox regression was used to identify factors significantly associated with overall survival. A total of 5,130 patients were identified with tumor grades 42% G1, 29% G2, 18% G3, and 13% unknown. Lymphovascular invasion (LVI) was present in a small number of patients (14.5%, absent 34.1%, unknown 51.5%). Approximately one quarter of patients were >70 years old (1,232; 24%) and had 1+ comorbidity (1,341; 26%). More than one in four patients (1,492; 29%) did not receive any planned adjuvant therapy. These patients were older >65 (49% vs. 38%), Medicare insured (47% vs 39%), had 1+ comorbidity (31% vs.24%), and lived >50 miles from a treating facility (19% vs 12 %). For adjuvant therapy, 1,231 (24%) had VBT alone, 1,231 (23.5%) PXRT+VBT, 886 (13%) PXRT alone, 140 (3%) mCT alone, and 137 (3%) PXRT+VBT+mCT. The use of mCT+ VBT tripled from 1.8% prior to 2009 to 6.2% after 2009, while PXRT+VBT decreased from 28% to 20.5% in the same time period (all p < 0.001). For the entire cohort, median follow-up was 58.7 mos (95% CI: 57.1–60.1 mos) and 5-yr OS was 79.5% (78.2–80.9%). By adjuvant treatment 5-yr OS was 87.4% VBT+mCT, 84.3% VBT alone, 83.3%, PXRT+VBT, 79.9% PXRT+VBT+mCT, 79.6% mCT, 78.1% PXRT alone, 72.2% surgery alone. On adjusted multivariate survival models, mCT+VBT was not associated with improved OS over PXRT+VBT (adjusted HR 0.68, p=0.1). All adjuvant regimens had a significant survival advantage when compared to surgery alone except mCT alone. In subgroup of elderly patients >70 years and the subgroup of patients with 1+ comorbidity, 35% and 31% patients respectively had no planned adjuvant therapy. These patients had significantly inferior OS compared to patients with AT (elderly: aHR 1.8 (1.5-2.2), p < 0.001; 1+ comorbidity aHR 2.0 (1.6-2.6), p<0.001). Adjuvant treatment for stage II endometrioid carcinoma is not administered to more than one quarter of patients in this national hospital-based. Patients without adjuvant treatment are older and have comorbidities. There appears to be survival benefit to adjuvant treatment in these populations.

A novel preoperative scoring system based on 18-FDG PET-CT for predicting lymph node metastases in patients with high-risk endometrial cancer

The purpose of this study was to develop a model predicting the probability of pelvic-paraaortic node metastases in high-risk endometrial cancer patients. This trial included 41 high-risk endometrial cancer patients. All of the patients underwent an 18-FDG PET-CT followed by surgical staging, including a pelvic and paraaortic lymphadenectomy. We developed a useful scoring system combining weighted risk factors derived from a regression model: (3 × presence PET-CT involvement) + (3 × PET-CT maximum standardised uptake value ≥20) + (2 × diabetes comorbidity) + (1 × age ≥60 years) + (1 × body mass index ≥30). The area under the curve of the resulting score was 0.848. There was 75% sensitivity, 89% specificity and a 75% positive predictive value and 89% negative predictive value when a score of 6 was used as the cut-off. Our novel preoperative scoring system is an accurate method for the preoperative evaluation of lymph node metastases, and thus will aid gynaecological oncologists in selecting EC patients who may benefit from a lymphadenectomy.Impact statementWhat is already known on this subject? Endometrial cancer (EC) is a common gynaecological malignancy. Surgical staging is currently the standard treatment and the gold standard for evaluating lymph node metastases (LNm) is a surgical assessment (Chan et al. 2006). Three previous randomised clinical studies failed to find a clear therapeutic role for the lymphadenectomy; thus, the utility of this surgical procedure in high-risk early-stage EC remains under debate (Benedetti Panici et al. 2008; Kitchener et al. 2009; Signorelli et al. 2015). Non-invasive techniques that accurately identify lymph node metastases would reduce costs and complications.What do the results of this study add? Our developed novel scoring system that is based on positron emission tomography-computer tomography (PET-CT) with 2-deoxy-2-(18F) flouro-2-D-glucose (FDG) may facilitate the identification of patients at an increased risk of LNm.What are the implications of these finding for clinical practice and/or further research? This study shows that our novel preoperative scoring system provides an accurate method for the preoperative evaluation of LNm, and thus could guide gynaecologic oncologists in selecting the high-risk endometrial cancer patients who may benefit from a systematic lymphadenectomy. Further larger, prospective studies are needed to confirm the accuracy and the feasibility of our scoring system.

Lymph node evaluation in high-risk early stage endometrial cancer: A multi-institutional retrospective analysis comparing the sentinel lymph node (SLN) algorithm and SLN with selective lymphadenectomy

ObjectiveThe aim of this study was to determine the impact of the sentinel lymph node mapping algorithm (SLN-A) on the staging in high-risk endometrial cancer (EC) compared to SLN plus selective lymphadenectomy (S-LND). MethodsWe retrospectively analyzed the database from a multicenter collaboration that included women with high risk features who underwent primary surgical staging. ResultsOne-hundred and seventy-one women were identified (171), 66 in the SLN-A and 105 in the S-LND group, respectively. Pelvic LD was performed on 115 patients (67.2%) and aortic dissection was performed in 54/105 of the women in the S-LND group (51%). The 5-year comparison did not show a significant difference in the strategy adopted for nodal staging, regarding disease-free survival (DFS) [HR: 0.82; 95% CI 0.53–1.28; p = 0.390]. ConclusionsIn this study focusing on women with EC in the HR groups, we did not find a difference in the 5-year DFS when comparing the SLN-A strategy with S-LND. The SLN strategy did not seem to compromise the prognosis of patients with a higher risk of recurrence.

Lymphadenectomy in Early-Stage Intermediate-/High-Risk Endometrioid Endometrial Cancer: Clinical Characteristics and Outcomes in an Australian Cohort.

The role of lymphadenectomy (LND) in early-stage endometrial cancer (EC) remains controversial. Previous studies have included low-risk patients and nonendometrioid histologies for which LND may not be beneficial, whereas long-term morbidity after LND is unclear. In a large Australian cohort of women with clinical early-stage intermediate-/high-risk endometrioid EC, we analyzed the association of LND with clinicopathological characteristics, adjuvant treatment, survival, patterns of disease recurrence, and morbidity. From a larger prospective study (Australian National Endometrial Cancer Study), we analyzed data from 328 women with stage IA grade 3 (n = 63), stage IB grade 1 to 3 (n = 160), stage II grade 1 to 3 (n = 71), and stage IIIC1/2 grade 1 to 3 (n = 31/3) endometrioid EC. Overall survival (OS) was estimated using Kaplan-Meier methods. The association of LND with OS was assessed using Cox regression analysis adjusted for age, stage, grade, and adjuvant treatment. The association with risk of recurrent disease was analyzed using logistic regression adjusted for age, stage, and grade. Morbidity data were analyzed using χ2 tests. Median follow-up was 45.8 months. Overall survival at 3 years was 93%. Lymphadenectomy was performed in 217 women (66%), 16% of this group having positive nodes. Median node count was 12. There were no significant differences in OS between LND and no LND groups, or by number of nodes removed. After excluding stage IB grade 1/2 tumors, there was no association between LND and OS among a "high-risk" group of 190 women with a positive node rate of 24%. However, a similar cohort (n = 71) of serous EC in the Australian National Endometrial Cancer Study had improved survival after LND. Women who underwent LND had significantly higher rates of critical events (5% vs 0%, P = 0.02) and lymphoedema (23% vs 4%, P < 0.0001). In this cohort with early-stage intermediate-/high-risk endometrioid EC, LND did not improve survival but was associated with significantly increased morbidity.

The Addition of Adjuvant Chemotherapy to Radiation in Early-Stage High-Risk Endometrial Cancer: Survival Outcomes and Patterns of Care.

Early-stage high-risk endometrial cancer (HREC) treated with adjuvant radiotherapy (aRT) alone has been associated with an increased risk of distant relapse. The addition of chemotherapy to radiotherapy (aCRT) may benefit overall survival (OS). We investigated the patterns-of-care and OS benefit of aCRT in HREC by analyzing a large national registry. Our query was limited to patients with the International Federation of Gynecology and Obstetrics stage IB and II HREC with either papillary serous, clear cell, or grade 3 adenocarcinoma, diagnosed between 2004 and 2012. Logistic and Cox regression analyses were utilized to identify predictors of aCRT use and OS, respectively. Survival analysis was performed with Kaplan Meier and log-rank methods. Propensity score matching was employed to decrease the potential influence of selection bias. A total of 11,746 patients were identified for analysis with 8206 (69.9%) receiving aCRT, and 3540 (30.1%) received aRT. Predictors of aCRT included International Federation of Gynecology and Obstetrics stage II (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.22-1.57), papillary serous (OR, 9.44; 95% CI, 8.22-10.85) or clear cell (OR, 3.21; 95% CI, 2.59-3.97) histology, lymph nodes removed (OR, 1.48; 95% CI, 1.31-1.69), and receipt of brachytherapy alone (OR, 1.55; 95% CI, 1.36-1.78). Estimated 5-year OS was 75.2% for patients receiving aRT only and 79.2% for those receiving aCRT (P < 0.001). When compared with aRT, aCRT was associated with improved OS on multivariate (hazard ratio, 0.78; 95% CI, 0.61-0.99) analysis. A univariate shared-frailty Cox regression after propensity score matching revealed persistence of the OS benefit with aCRT (hazard ratio, 0.74; 95% CI, 0.65-0.84). The addition of adjuvant chemotherapy to radiation in HREC is associated with improved OS. Multiple demographic and clinical factors significantly influence the choice of adjuvant therapy in this setting.