Intermediate Risk Endometrial Cancer Research Articles

Intermediate-risk endometrial cancer treated with adjuvant brachytherapy using single dosimetric planning: long-term outcome and toxicity assessment

ObjectiveBrachytherapy of the vaginal dome is the recommended adjuvant treatment for intermediate-risk endometrial cancer. This study assessed the results of dosimetric planning of high-dose-rate brachytherapy exclusively in the first treatment session.Study design: This retrospective study included all patients who underwent hysterectomy for endometrial cancer followed by adjuvant brachytherapy of the vaginal dome between 2012 and 2015. Local recurrence rates, overall survival (OS) rates, recurrence-free survival (RFS) rates, and related acute and late toxicity rates were evaluated. ResultsThis analysis included 250 patients, of whom 208 were considered to be at high–intermediate risk of disease recurrence. After a median follow-up of 56 months, the cumulative incidence of local recurrence was 4.8% at 3 years [95% confidence interval (CI) 2.8–8.3] and 7.8% at 5 years (95% CI 4.8–12.6). The 5-year OS rate was 86.2% (95% CI 80.6–90.3), and the 5-year RFS rate was 77.5% (95% CI 71.1–82.7). Acute toxicity occurred in 20 (8%) patients, of which two patients had grade ≥3 toxicity. Only one patient (0.4%) presented with late grade ≥3 toxicity. ConclusionThese findings confirm the tolerability of this brachytherapy approach, indicating minimal cases of late grade ≥3 toxicity, associated with a good 5-year OS rate. With the advent of molecular prognostic factors, the current focus revolves around discerning those individuals who gain the greatest benefit from adjuvant therapy, and tailoring treatment more effectively.

Tailoring postoperative management through sentinel lymph node biopsy in low- and intermediate-risk endometrial cancer - the SENTRY clinical trial.

While total hysterectomy and bilateral salpingo-oophorectomy without lymph node staging are standard for low- and intermediate-risk endometrial cancer, certain histopathologic factors revealed after surgery can necessitate additional interventions. Our study assessed the influence of sentinel lymph node biopsy on postoperative decision-making. In the SENTRY trial (July 2021 - February 2023), we enrolled patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IA-IB low-grade endometrioid endometrial cancer. Laparoscopic sentinel lymph node mapping using indocyanine green was performed alongside total hysterectomy with bilateral salpingo-oophorectomy. Subsequent management changes based on sentinel lymph node biopsy results were evaluated. The trial was registered at ClinicalTrials.gov (NCT04972682). Of the 100 enrolled participants, a bilateral detection rate of 91% was observed with a median detection time of 10 min (interquartile range 8-13 min). Sentinel lymph node metastases were found in 8% (N = 8) of participants. Postoperative FIGO staging increased in 15% (N = 15) and decreased in 5% (N = 5) of patients. Sentinel lymph node biopsy results altered the adjuvant treatment plan for 20% (N = 20): external beam radiotherapy was omitted in 12% (N = 12) while 6% (N = 6) had external beam radiotherapy +/- systemic chemotherapy added due to sentinel lymph node metastases. In 2% (N = 2), the external beam radiotherapy field was expanded with the paraaortic region. No intraoperative complications were reported and no 30-day major morbidity and mortality occurred. Throughout a median follow-up of 14 (95% CI 12-15 months, neither patient-reported lymphedema nor pelvic recurrence surfaced in the cohort. Sentinel lymph node biopsy using indocyanine green is a safe procedure and allows tailoring adjuvant therapy in presumed low- and intermediate-risk endometrial cancer. It assists in avoiding external beam radiotherapy overtreatment and introducing additional modalities when necessary.

Prognostic impact and causality of age on oncological outcomes in women with endometrial cancer: a multimethod analysis of the randomised PORTEC-1, PORTEC-2, and PORTEC-3 trials

Numerous studies have shown that older women with endometrial cancer have a higher risk of recurrence and cancer-related death. However, it remains unclear whether older age is a causal prognostic factor, or whether other risk factors become increasingly common with age. We aimed to address this question with a unique multimethod study design using state-of-the-art statistical and causal inference techniques on datasets of three large, randomised trials. In this multimethod analysis, data from 1801 women participating in the randomised PORTEC-1, PORTEC-2, and PORTEC-3 trials were used for statistical analyses and causal inference. The cohort included 714 patients with intermediate-risk endometrial cancer, 427 patients with high-intermediate risk endometrial cancer, and 660 patients with high-risk endometrial cancer. Associations of age with clinicopathological and molecular features were analysed using non-parametric tests. Multivariable competing risk analyses were performed to determine the independent prognostic value of age. To analyse age as a causal prognostic variable, a deep learning causal inference model called AutoCI was used. Median follow-up as estimated using the reversed Kaplan-Meier method was 12·3 years (95% CI 11·9-12·6) for PORTEC-1, 10·5 years (10·2-10·7) for PORTEC-2, and 6·1 years (5·9-6·3) for PORTEC-3. Both overall recurrence and endometrial cancer-specific death significantly increased with age. Moreover, older women had a higher frequency of deep myometrial invasion, serous tumour histology, and p53-abnormal tumours. Age was an independent risk factor for both overall recurrence (hazard ratio [HR] 1·02 per year, 95% CI 1·01-1·04; p=0·0012) and endometrial cancer-specific death (HR 1·03 per year, 1·01-1·05; p=0·0012) and was identified as a significant causal variable. This study showed that advanced age was associated with more aggressive tumour features in women with endometrial cancer, and was independently and causally related to worse oncological outcomes. Therefore, our findings suggest that older women with endometrial cancer should not be excluded from diagnostic assessments, molecular testing, and adjuvant therapy based on their age alone. None.

Symptomatic Lymphocele After Robot-Assisted Pelvic Lymphadenectomy as Part of the Primary Surgical Treatment for Cervical and Endometrial Cancer: A Retrospective Cohort Study

Pelvic lymph node dissection (PLND) is part of the primary treatment for early-stage cervical cancer and high-intermediate risk or high-risk endometrial cancer. Pelvic lymphocele is a postoperative complication of PLND and when symptomatic, lymphoceles necessitate treatment. The aim of this study was to investigate the incidence and risk factors of symptomatic lymphocele after robot-assisted laparoscopic PLND in cervical and endometrial cancer. Retrospective cohort study. Single-center academic hospital. Two hundred and fifty-eight patients with cervical cancer and one hundred and twenty-nine patients with endometrial cancer. Pelvic lymphadenectomy by robot-assisted laparoscopic surgery. We retrospectively included all patients with early-stage cervical cancer and high- intermediate risk or high-risk endometrial cancer who underwent pelvic lymphadenectomy by robot-assisted laparoscopic surgery between 2008 and 2022. Medical records were reviewed for the occurrence of a symptomatic lymphocele. Univariate and multivariate logistic regression analyses were conducted to identify risk factors for developing a symptomatic lymphocele. In total 387 patients, 258 with cervical cancer and 129 with endometrial cancer, were included in the study. The overall incidence of symptomatic lymphoceles was 9.6% with a median follow-up of 47 months [IQR 23-61]. For the entire cohort, smoking was the only significant risk factor for symptomatic lymphoceles identified in univariate (OR 2.47, 95% CI 1.19-5.11) and multivariate analysis (OR 2.42, 95% CI 1.16-5.07). For cervical cancer, BMI (OR 1.09, 95% CI 1.00-1.17) and prior abdominal surgery (OR 2.75, 95% CI 1.22-6.17) were also identified as significant independent risk factors. For endometrial cancer, age was identified as significant independent risk factor (OR 0.90, 95% CI 0.83-0.97). This single-center cohort study demonstrated an incidence of almost 10% of symptomatic lymphoceles after robot-assisted laparoscopic PLND for cervical cancer and endometrial cancer, with a higher risk observed among patients who smoke at the time of diagnosis. Furthermore, risk factors differ between the two populations, necessitating further studies to establish risk models.

Treatment outcomes of early-stage endometrial cancer patients: A propensity score matching of vaginal brachytherapy versus pelvic radiotherapy.

This study aimed to report the treatment outcomes of radiation therapy for early-stage endometrial cancer patients. In addition, this study intended to identify high-risk factors that require pelvic radiotherapy (PRT) in addition to vaginal brachytherapy (VBT) for intermediate-risk endometrial cancer patients. Patients with early-stage endometrial cancer receiving postoperative VBT alone or with PRT were included. Propensity score matching was used to balance the two study groups. The primary endpoint was locoregional recurrence (LRR). Age-adjusted Charlson comorbidity index and substantial lymphovascular space invasion were selected for subgroup analyses to identify the benefits of PRT over VBT alone. From 2005 to 2017, a total of 288 patients underwent analysis following propensity score matching. Of these, 144 received VBT and 144 received PRT. There was no significant difference in 5-year LRR between VBT and PRT for both intermediate (0% vs. 0%) and high-intermediate risk patients (3.5% VBT vs. 5.4% PRT; HR 0.54: 0.05-6.00; p = 0.616). The subgroup analyses revealed no significant factors favoring PRT over VBT. Patients with high comorbidities may have higher risks of non-cancer death after receiving PRT. Postoperative VBT alone is sufficient for early-stage intermediate-risk endometrial cancer patients.

Cost-effectiveness of POLE testing for high intermediate risk endometrial cancer (2242)

Cost-effectiveness of POLE testing for high intermediate risk endometrial cancer (2242)

Molecular Classification Predicts Response to Radiotherapy in the Randomized PORTEC-1 and PORTEC-2 Trials for Early-Stage Endometrioid Endometrial Cancer.

The molecular classification of endometrial cancer (EC) has proven to have prognostic value and is predictive of response to adjuvant chemotherapy. Here, we investigate its predictive value for response to external beam radiotherapy (EBRT) and vaginal brachytherapy (VBT) in early-stage endometrioid EC (EEC). Data of the randomized PORTEC-1 trial (n = 714) comparing pelvic EBRT with no adjuvant therapy in early-stage intermediate-risk EC and the PORTEC-2 trial (n = 427) comparing VBT with EBRT in early-stage high-intermediate-risk EC were used. Locoregional (including vaginal and pelvic) recurrence-free survival was compared between treatment groups across the four molecular classes using Kaplan-Meier's methodology and log-rank tests. A total of 880 molecularly classified ECs, 484 from PORTEC-1 and 396 from PORTEC-2, were included. The majority were FIGO-2009 stage I EEC (97.2%). The median follow-up was 11.3 years. No locoregional recurrences were observed in EC with a pathogenic mutation of DNA polymerase-ε (POLEmut EC). In mismatch repair-deficient (MMRd) EC, locoregional recurrence-free survival was similar after EBRT (94.2%), VBT (94.2%), and no adjuvant therapy (90.3%; P = .74). In EC with a p53 abnormality (p53abn EC), EBRT (96.9%) had a substantial benefit over VBT (64.3%) and no adjuvant therapy (72.2%; P = .048). In EC with no specific molecular profile (NSMP EC), both EBRT (98.3%) and VBT (96.2%) yielded better locoregional control than no adjuvant therapy (87.7%; P < .0001). The molecular classification of EC predicts response to radiotherapy in stage I EEC and may guide adjuvant treatment decisions. Omitting radiotherapy seems to be safe in POLEmut EC. The benefit of radiotherapy seems to be limited in MMRd EC. EBRT yields a significantly better locoregional recurrence-free survival than VBT or no adjuvant therapy in p53abn EC. VBT is the treatment of choice for NSMP EC as it is as effective as EBRT and significantly better than no adjuvant therapy for locoregional tumor control.

The SENTIREC-endo study – Risks and benefits of a national adoption of sentinel node mapping in low and intermediate risk endometrial cancer

ObjectiveThe SENTIREC-endo study aims to investigate risks and benefits of a national protocolled adoption of sentinel lymph node (SLN) mapping in women with early-stage low-grade endometrial cancer (EC) with low- (LR) and intermediate-risk (IR) of lymph node metastases. MethodsWe performed a national multicenter prospective study of SLN-mapping in women with LR and IR EC from March 2017–February 2022. Postoperative complications were classified according to Clavien-Dindo. Lymphedema was assessed as a change score and as incidence of swelling and heaviness evaluated by validated patient-reported outcome measures at baseline and three months postoperatively. Results627 women were included in the analyses; 458 with LR- and 169 with IR EC. The SLN detection rate was 94.3% (591/627). The overall incidence of lymph node metastases was 9.3% (58/627); 4.4% (20/458) in the LR- and 22.5% (38/169) in the IR group. Ultrastaging identified 62% (36/58) of metastases. The incidence of postoperative complications was 8% (50/627) but only 0.3% (2/627) experienced an intraoperative complication associated with the SLN procedure. The lymphedema change score was below the threshold for clinical importance 4.5/100 CI: (2.9–6.0), and the incidence of swelling and heaviness was low; 5.2% and 5.8%, respectively. ConclusionSLN mapping in women with LR and IR EC carries a very low risk of early lymphedema and peri- and postoperative complications. The national change in clinical practice contributed to a more correct treatment allocation for both risk groups and thus supports further international implementation of the SLN technique in early stage, low grade EC.

Sentinel Lymph Node Mapping in Presumed Low- and Intermediate-Risk Endometrial Cancer Management (SLIM): A Multicenter, Prospective Cohort Study in The Netherlands.

The aim was to investigate the incidence of sentinel lymph node (SLN) metastases and the contribution of SLN mapping in presumed low- and intermediate-risk endometrial cancer (EC). A multicenter, prospective cohort study in presumed low- and intermediate-risk EC patients was performed. Patients underwent SLN mapping using cervical injections of indocyanine green and a minimally invasive hysterectomy with bilateral salpingo-oophorectomy. The primary outcome was the incidence of SLN metastases, leading to adjusted adjuvant treatment. Secondary outcomes were the SLN detection rate and the occurrence of complications. Descriptive statistics and univariate general linear model analyses were used. A total of 152 patients were enrolled, with overall and bilateral SLN detection rates of 91% and 61%, respectively. At final histology, 78.9% of patients (n = 120) had truly low- and intermediate-risk EC. Macro- and micro-metastases were present in 11.2% (n = 17/152), and three patients had isolated tumor cells (2.0%). Nine patients (5.9%) had addition of adjuvant radiotherapy based on SLN metastases only. In 2.0% of patients with high-risk disease, adjuvant therapy was more limited due to negative SLNs. This study emphasizes the importance of SLN mapping in presumed early-stage, grade 1 and 2 EC, leading to individualized adjuvant management, resulting in less undertreatment and overtreatment.

Reassessment of low- and intermediate-risk endometrial cancer reports by gynecological pathologists increases risk classification without impacting outcome

ObjectivesA lack of agreement is often observed in pathological reviews performed by specialized and general pathologists. Four histopathological variables influence the risk classification of endometrial cancer: histological type; histological grade; myometrial invasion; lymph-vascular space invasion (LVSI). This study aimed to evaluate if changes in the risk classification after a specialized pathological review of low- and intermediate-risk endometrial cancer (LIREC) samples may impact disease-free survival (DFS). MethodsA retrospective cohort of 195 patients diagnosed with LIREC at Barretos Cancer Hospital was obtained. Two gynecologic pathologists re-evaluated the pathological reports. Through the histology report reviewed, we could determine their new risk classification. The Kappa concordance score was used to verify the concordance between the general’s and specialized pathologists’ reports, and the new risk classification was correlated with the patients’ DFS. ResultsThe final reports led to changes in the histological type, histological grade, myometrial invasion, and lymphovascular space invasion in 13.3 %, 62,8%, 18.3 %, and 11.1 % of cases, respectively. The Kappa concordance score for all variables was less than 0.7. In 54 patients (30 %), the risk classification was modified (κ = 0.396), of which 30 (55.5 %) cases upstaged. There was no difference in DFS for patients who had an upstaging in their European Society of Medical Oncology modified classification compared to those who maintained their initial risk classification (86.7 % vs 88.0 %, p = 0.77). ConclusionDespite the differences in the reports reassessed by expert gynecological pathologists and the change (30%) in patients' risk classification, there was no difference in their DFS.

PO-1357 Comorbidity index and LVSI for treatment selection for intermediate risk endometrial cancer patients

PO-1357 Comorbidity index and LVSI for treatment selection for intermediate risk endometrial cancer patients

664 Laparoscopic sentinel lymph node dissection in patients with high-intermediate risk endometrial cancer and serious comorbidity

Introduction and aims of the study: Sentinel lymph node dissection (SLND) is an alternative procedure in surgical staging of patients with intermediate risk endometrial cancer. Data about use of this technique in patients with high-intermediate risk endometrial cancer and serious comorbidity is insufficient. Methods: The retrospective study included 24 patients with high intermediate risk endometrial cancer (endometrioid adenocarcinoma FIGO stage IA, grade 3 (n=15) and stage IA, grade 1-2, LVSI+ (n=9).

The added value of SLN mapping with indocyanine green in low- and intermediate-risk endometrial cancer management: a systematic review and meta-analysis

ObjectiveThe aim of this study was to assess the SLN detection rate in presumed early stage, low- and intermediate-risk endometrial cancers, the incidence of SLN metastases, and the negative predictive value of SLN mapping performed with indocyanine green (ICG).MethodsA systematic review with meta-analyses was conducted. Study inclusion criteria were A) low- and intermediate-risk endometrial cancer, B) the use of ICG per cervical injection; C) a minimum of twenty included patients per study. To assess the negative predictive value of SLN mapping, D) a subsequent lymphadenectomy was an additional inclusion criterion.ResultsFourteen studies were selected, involving 2,117 patients. The overall and bilateral SLN detection rates were 95.6% (95% confidence interval [CI]=92.4%–97.9%) and 76.5% (95% CI=68.1%–84.0%), respectively. The incidence of SLN metastases was 9.6% (95% CI=5.1%–15.2%) in patients with grade 1–2 endometrial cancer and 11.8% (95% CI=8.1%–16.1%) in patients with grade 1–3 endometrial cancer. The negative predictive value of SLN mapping was 100% (95% CI=98.8%–100%) in studies that included grade 1–2 endometrial cancer and 99.2% (95% CI=97.9%–99.9%) in studies that also included grade 3.ConclusionSLN mapping with ICG is feasible with a high detection rate and negative predictive value in low- and intermediate-risk endometrial cancers. Given the incidence of SLN metastases is approximately 10% in those patients, SLN mapping may lead to stage shifting with potential therapeutic consequences. Given the high negative predictive value with SLN mapping, routine lymphadenectomy should be omitted in low- and intermediate-risk endometrial cancer.

Ultrastaging of ‘negative’ pelvic lymph nodes in patients with low- and intermediate-risk endometrioid endometrial cancer who developed non-vaginal recurrences

ObjectiveEvidence on micrometastases and isolated tumor cells as factors associated with non-vaginal recurrence in low- and intermediate-risk endometrial cancer is limited. The goal of our study was to investigate risk...

58: Use of Robotic Hysterectomy in Intermediate-Risk Endometrial Cancer

58: Use of Robotic Hysterectomy in Intermediate-Risk Endometrial Cancer

A 4-Gene Signature Associated With Recurrence in Low- and Intermediate-Risk Endometrial Cancer.

BackgroundThe molecular profile of endometrial cancer has become an important tool in determining patient prognosis and their optimal adjuvant treatment. In addition to The Cancer Genome Atlas (TCGA), simpler tools have been developed, such as the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE). We attempted to determine a genetic signature to build a recurrence risk score in patients diagnosed with low- and intermediate-risk endometrial cancer.MethodsA case-control study was conducted. The eligible patients were women diagnosed with recurrence low- and intermediate-risk endometrial cancer between January 2009 and December 2014 at a single institution; the recurrence patients were matched to two nonrecurrence patients with the same diagnosis by age and surgical staging. Following RNA isolation of 51 cases, 17 recurrence and 34 nonrecurrence patients, the expression profile was determined using the nCounter® PanCancer Pathways Panel, which contains 770 genes.ResultsThe expression profile was successfully characterized in 49/51 (96.1%) cases. We identified 12 genes differentially expressed between the recurrence and nonrecurrence groups. The ROC curve for each gene was generated, and all had AUCs higher than 0.7. After backward stepwise logistic regression, four genes were highlighted: FN1, DUSP4, LEF1, and SMAD9. The recurrence risk score was calculated, leading to a ROC curve of the 4-gene model with an AUC of 0.93, sensitivity of 100%, and specificity of 72.7%.ConclusionWe identified a four-gene signature that may be associated with recurrence in patients with low- and intermediate-risk endometrial cancer. This finding suggests a new prognostic factor in this poorly explored group of patients with endometrial cancer.

Effect of mismatch repair protein status on outcomes in high intermediate risk endometrial cancer

<h3>Objectives:</h3> To compare recurrence rates between patients with mismatch repair proficient (pMMR) and MMR deficient (dMMR) high intermediate risk (HIR) endometrial cancer <h3>Methods:</h3> Adult women with HIR endometrial cancer diagnosed between January 1, 2016, and December 31, 2018, were identified from UC San Diego and Kaiser Southern California. Patient and disease characteristics were collected by chart review. Cases were limited to those who underwent hysterectomy with endometrioid histology and stage 1 disease. HIR disease was defined as the presence of three risk factors if age < 50 years, two risk factors if age ≥50 and <70 years, and one risk factor if age ≥70 years. Risk factors included tumor grade 2 or 3, the presence of lymphovascular space invasion (LVSI), and ≥50% myometrial invasion as outlined in GOG protocol 249. Categorical variables were compared using Chi-square tests, and continuous variables were compared using Student's t-test. The Kaplan-Meier method was used to evaluate time to recurrence. Assuming a two-sided alpha error of 0.05, power calculation identified a sample size of 174 would be needed to detect a 0.15 difference in recurrence rates between cohorts with 80% power. <h3>Results:</h3> Two hundred forty-four patients with HIR endometrial cancer were identified during the study period. One hundred fifty-eight patients (65%) were pMMR by immunohistochemical staining, and 86 patients (35%) were dMMR. There were no differences in mean age, mean body mass index (BMI), race, grade, mean follow-up time, or type of adjuvant treatment received between the pMMR versus dMMR cohorts. In total, 40 (16%) patients experienced cancer recurrence, and there were 11 (4.5%) cancer-related deaths during the study period. There was no statistically significant difference in recurrence rates between the pMMR and dMMR cohorts (15% versus 19%, p=0.49). The lack of association between MMR status and recurrence persisted after controlling for depth of myometrial invasion and LVSI in logistic regression multivariable analysis. pMMR tumors were more likely to exhibit ≥50% myometrial invasion than patients with dMMR tumors (p=0.03). dMMR tumors were significantly more likely to exhibit LVSI than pMMR tumors (p<0.001). There was no statistically significant association between the type of adjuvant treatment received and MMR status among those who recurred (p=0.58). Among patients who recurred, site of first recurrence (local vs distant) was not associated with MMR status (p=.90). The mean time to recurrence was 531 days in the pMMR cohort (n=24) and 473 days in the dMMR cohort (n=16), which was not significantly different (p=0.28). <h3>Conclusions:</h3> Our analysis represents one of the largest recurrence rate analyses of HIR endometrial cancer as stratified by MMR status. Although our pMMR and dMMR patient cohorts with HIR did not differ with respect to patient characteristics, dMMR tumors were significantly more likely to have <50% myometrial invasion and to exhibit LVSI. Despite these differences, we observed no difference in recurrence rates or time to recurrence between the two groups, which is in contrast to previously published reports of better prognosis among patients with pMMR tumors. Further study is ongoing to evaluate the effect of mismatch repair status on treatment selection and patient outcomes.

The 10-year results after national introduction of pelvic lymph node staging in Danish intermediate-risk endometrial cancer patients not given postoperative radiotherapy

The 10-year results after national introduction of pelvic lymph node staging in Danish intermediate-risk endometrial cancer patients not given postoperative radiotherapy. Gitte Ørtoft; Claus Høgdall; Estrid S Hansen; Margit Dueholm. ObjectiveTo prepare for the national introduction of sentinel node staging, we evaluated the consequences of the previous national decision to introduce lymph node staging in intermediate-risk endometrial cancer patients (grade 1/2 with > 50% or grade 3 with < 50% myometrial invasion) by determining the number of patients upstaged by lymphadenectomy and whether upstaging affected the survival and recurrence patterns of non-staged patients and patients with and without lymph node metastases. Study DesignIn a national cohort study, 2005–12, 1294 stage I–IV patients who should have been offered lymphadenectomy were progressively registered. The number of patients upstaged by lymphadenectomy, 10-year survivals were evaluated by Kaplan–Meier analysis and adjusted Cox regression. ResultsThis study demonstrates that it takes time to introduce lymphadenectomy at a national level, as indicated by the increasing number of cases staged per year, from 12% in 2005 to 74% in 2012. Pelvic lymphadenectomy was performed in 43.8% (567/1294) and lymph node metastases were found in 13.6% (77/567). As 54 patients had further dissemination outside the uterine body, only 23 patients (6%) were upstaged from stage I to IIIC. Compared to lymph node-negative patients, the 77 patients with lymph node metastasis had significantly lower overall, (55% versus 68%), disease-specific (64% versus 86%), and progression-free survival (51% versus 77%), mainly due to non-local recurrences including a high number of paraaortic recurrences. In 873 final stage I intermediate-risk patients, 10-year survival and recurrence rates were not significantly lower in non-staged as compared to lymph node-negative patients (overall survival 62% versus 70%: disease-specific survival: 90% versus 90%, progression-free survival: 81% vs 83%), probably due to the low number of patients upstaged from stage I to stage IIIC. ConclusionLymph node metastases were present in 13.6% of patients with intermediate-risk who underwent pelvic lympadenectomy, and these patients had a lower 10-year survival than lymph node-negative patients. Because lymphadenectomy upstaged only 6% from stage I to stage IIIC, survival and recurrence rates were not significantly compromised in non-staged as compared to lymph node-negative intermediate-risk stage I patients. Sentinel node staging has now been implemented in Danish intermediate-risk endometrial cancer patients.

A longitudinal study of the adherence to PORTEC-2 based adjuvant radiotherapy in high-intermediate-risk endometrial adenocarcinoma and associated oncologic outcomes.

e17570 Background: In 2010, Nout et al. reported on PORTEC-2, which randomized patients with high intermediate risk (HIR) endometrial cancer to adjuvant vaginal brachytherapy or pelvic radiotherapy or observation, and showed that vaginal brachytherapy was non-inferior in terms of locoregional control and was deemed the adjuvant treatment of choice for these patients. We sought to evaluate the adherence to and the oncologic outcomes of the PORTEC-2 regimen. Methods: We utilized the SEER database to identify patients who met PORTEC-2 inclusion criteria. All patients underwent surgery followed by either vaginal brachytherapy (VBT) or whole pelvic radiotherapy (WPRT). Inclusion criteria were patients with the following characteristics: grade 1 with ≥ 50% myometrial invasion (MI), grade 2 with any invasion, and grade 3 with &lt; 50% MI. Patients were excluded if any lymph nodes were examined or involved, if they received any chemotherapy, or had any missing values for any of the variables. HIR endometrial adenocarcinoma was defined as the presence of 2 of the following: age &gt; 60, grade 3, and ≥50% myometrial invasion. Radiation status was extracted from the SEER Radiation/Chemotherapy database. Outcomes were overall death, cancer specific death and total survival months per SEER’s standard definitions. Variables are reported as median and interquartile range (IQR) or number (%). Mean survival was calculated using Kaplan Meier analysis and Mantel-Cox rank test was done to test for statistical significance between the study groups. Cox regression analysis was performed, and hazard ratios (HR) were calculated. Statistical analysis was performed using SPSS v. 22.0. Results: Between 2005- 2015, 571 patients met PORTEC-2 inclusion criteria of whom 349 (61.1%) and 222 (38.9%) received WPRT and VBT, respectively. We showed that the rate of VBT was significantly increased from 85 (27.4%) between 2005-2010 to 137 (52.5%) between 2011-2015 (p &lt; 0.001). There was no difference in grade and myometrial invasion between the study groups. Kaplan Meier analysis showed a 22.5 and 16.3 month improvement in overall and cancer specific survival in subjects who underwent VBT as compared to WPRT, respectively (p &lt; 0.001 for both). Cox regression analysis revealed a 36% and 66% decrease in the hazard of overall and cancer specific death, respectively, in the VBT group as compared to WPRT group (Overall death: HR = 0.64, 95% CI: 0.45-0.91, p = 0.012; Cancer specific death: HR = 0.34, 95% CI: 0.16-0.73, p = 0.006). Conclusions: Administration of vaginal brachytherapy following surgery has become significantly more popular after publication of the PORTEC-2 results in 2010. Our study shows a significant decrease in both overall and cancer related death and an increase in survival with VBT over WPRT in patients with HIR endometrial cancer.

Avoiding Full Lymphadenectomies in Intermediate- and High-Risk Endometrial Cancer by Sentinel Lymph Node Biopsy Implementation.

ObjectiveTo evaluate the role of sentinel lymph node biopsy (SLNB) to avoid staging lymphadenectomies by detecting nodal metastasis in intermediate- and high-risk endometrial cancer (EC).MethodsA single institutional retrospective study was performed including all patients with intermediate- and high-risk EC who underwent surgical nodal staging between January 2012 and December 2019. Patients with disseminated disease detected on imaging techniques or at the time of surgery were excluded. Patients were evaluable if they underwent nodal staging with SLNB and pelvic (PLD) and paraaortic (PALD) lymph node dissection. We analyzed the accuracy of the sentinel lymph node technique. Only patients with at least one sentinel lymph node (SLN) detected were included in the sensitivity and negative predictive value (NPV) analyses. The tracers used were technetium 99m, blue dye, and indocyanine green.ResultsEighty-eight patients presented intermediate- and high-risk EC (51 patients and 37 patients respectively) and underwent SLNB with consecutive PLD and PALD. The median (range) number of sentinel nodes retrieved was 2.9 (0–11). The global detection rate of SLN was 96.6% with a bilateral detection of 80.7% when considering all tracers used. However, when combination of indocyanine green and technetium was used the bilateral detection rate was 90.3%. Nodal metastases were detected in 17 (19.3%) cases, 8 (47%) of them corresponded to low volume metastasis (LVM), 7 (87.5%) of them diagnosed at ultrastaging pathologic exam. Finally, we obtained a sensitivity of 90%, a NPV of 97.5%, and a false negative rate (FNR) of 10% in the intermediate-risk EC compared to sensitivity of 85.7%, NPV of 96.6%, and FNR of 14.3% in the high-risk EC group. The only patient with isolated paraaortic nodal metastasis was found at the high-risk group, 1.1%.ConclusionsAccording to our results, full lymphadenectomy could be avoided by performing SLNB in patients with intermediate-risk EC because the only false negative case detected was at the beginning of ICG learning curve. For high-risk EC patients we did not find enough evidence to support the systematic avoidance of staging full lymph node dissection. Nevertheless, SLNB should be performed in all cases of EC as it improves LVM diagnosis substantially.