Stage IIIC Endometrial Cancer Research Articles

Chemotherapy before radiation for women with stage IIIC endometrial cancer receiving combined adjuvant chemotherapy and radiation

Objective: It is unclear how to best sequence adjuvant treatment for women with advanced endometrial cancer receiving both chemotherapy and radiation. The goal of this study was to review the outcomes for women treated with chemotherapy before radiation.

Lymph Node Number Predicts the Efficacy of Adjuvant Chemoradiotherapy in Node-Positive Endometrial Cancer Patients.

This study aimed to evaluate the value of lymph node (LN) number as a predictor for adjuvant treatment in node-positive endometrial cancer. Data of 441 patients diagnosed with International Federation of Gynaecology and Obstetrics (FIGO) stage IIIC endometrial cancer and who underwent adjuvant chemotherapy alone or chemoradiotherapy between 2009 and 2015 from the Taiwan Cancer Registry were reviewed. The patients were stratified based on the number of positive LN as follows: 1, 2–5, and ≥ 6. The overall survival (OS) was analysed using the Kaplan–Meier method and the Cox proportional hazards model. In multivariable analysis, chemoradiotherapy was independently associated with improved OS (hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.43–0.90; p = 0.01) compared with chemotherapy alone. Patients with ≥ 6 positive LNs were associated with a worse OS (HR: 2.22, 95% CI: 1.25–3.95; p = 0.006) and those with 2–5 LNs were not associated with a worse OS (HR: 1.56, 95% CI: 0.94–2.59; p = 0.09) compared to patients with one LN. When stratified based on LN number, chemoradiotherapy was found to significantly improve the 5-year OS of patients with ≥ 6 positive LNs compared to chemotherapy alone (35.9% vs. 70.0%, p < 0.001). No significant differences between chemotherapy alone and chemoradiotherapy were observed in 5-year OS among patients with one LN (73.1% vs. 80.8%, p = 0.31) or 2–5 positive LNs (71.4% vs. 75.7%, p = 0.68). Lymph node number may be used to identify node-positive endometrial cancer patients who are likely to have improved OS with intensification of adjuvant therapy.

Impact of different adjuvant treatment approaches on survival in stage III endometrial cancer: A population-based study

BackgroundPatients with International Federation of Gynaecology and Obstetrics (FIGO) stage III endometrial cancer (EC) have a substantial risk of adverse outcomes. After surgery, adjuvant therapy is recommended with external beam radiotherapy (EBRT), chemotherapy (CT) or both EBRT and CT. Recent trials suggest that EBRT + CT is superior to EBRT or CT alone but also results in more toxicity. We have compared the outcome of different adjuvant treatments in a population-based cohort to identify subgroups that benefit most from EBRT + CT. MethodsAll patients diagnosed with FIGO stage III EC and treated with surgery in 2005–2016 were identified from the Netherlands Cancer Registry. The primary outcome was overall survival (OS); associations with adjuvant treatment were analysed using Cox regression analysis. ResultsAmong 1241 eligible patients, EBRT + CT was associated with a better OS than CT (hazard ratio [HR] = 1.84, 95% confidence interval [CI] = 1.34–2.52) and EBRT alone (HR = 1.37, 95% CI = 1.05–1.79). In stage IIIC, there was a significant benefit of EBRT + CT compared with CT or EBRT alone. In stage IIIA–B, there was no difference between EBRT + CT or EBRT alone. In endometrioid EC (EEC) and carcinosarcomas, EBRT + CT was associated with a better OS than CT or EBRT alone. For uterine serous cancers, there was no survival benefit of EBRT + CT over CT. In all analysis by stage and histology, any adjuvant treatment was superior to no adjuvant therapy. ConclusionsIn this population-based study, adjuvant EBRT + CT was associated with improved OS compared with CT or EBRT alone in FIGO stage IIIC EC, EEC and carcinosarcoma. This suggests that application of EBRT + CT in stage III should be further stratified according to these subgroups.

The characteristics of isolated para-aortic lymph node metastases in endometrial cancer and their prognostic significance.

Background:The aim of this study was to clarify the features and prognostic significance of isolated para-aortic lymphatic metastasis of endometrial cancer.Methods:A retrospective study of patients with stage IIIC endometrial cancer was performed based on the Surveillance, Epidemiology, and End Results (SEER) database. A total of 2767 patients were divided into three groups according to the lymphatic metastasis patterns: isolated pelvic lymphatic metastasis, isolated para-aortic lymphatic metastasis and dual lymphatic metastasis. The clinic-pathological characteristics and prognosis of patients were compared among the three groups.Result:The proportion of patients with isolated para-aortic lymphatic metastasis was 13.70%. Patients with isolated pelvic lymphatic metastasis or isolated para-aortic lymphatic metastasis shared similar histological characteristics, except that patients with isolated para-aortic lymphatic metastasis had a lower proportion of tumors over 5 cm in diameter than patients with isolated pelvic lymphatic metastasis (35.1% versus 45.7%, p = 0.001). Compared with patients with dual lymphatic metastasis, isolated para-aortic lymphatic metastasis was more common in patients with endometrioid tumors (78.6% versus 67.3%, p < 0.001), grade 1–2 cancers (53.3% versus 36.3%, p < 0.001) and negative peritoneal cytology (76.2% versus 61.1%, p < 0.001). Dual lymphatic metastasis was an independent predictive factor for the poor outcomes of patients at stage IIIC. However, in stage IIIC endometrioid tumors, patients with isolated pelvic lymphatic metastasis and those with isolated para-aortic lymphatic metastasis shared similar prognosis. Patients at stage IIIC with nonendometrioid tumors and patients at stage IV could not be further divided into subgroups according to lymphatic metastasis patterns in terms of prognosis.Conclusion:Endometrioid patients with isolated pelvic lymphatic metastasis and isolated para-aortic lymphatic metastasis share similar clinical pathological characteristics and prognoses.

Is there any benefit of paraaortic field irradiation in pelvic lymph node positive endometrial cancer patients? A propensity match analysis

We evaluated the survival outcomes and recurrence patterns of endometrial cancer (EC) patients with pelvic lymph node metastases who received postoperative radiotherapy (RT) to the pelvis (P-RT) or to the pelvis plus paraaortic lymph nodes (PA-RT) with or without systemic chemotherapy (ChT). The data from 167 patients with stage IIIC1 EC treated with postoperative RT or RT and ChT were collected retrospectively. Those patients with pelvic lymph node metastases were treated with either P-RT (106 patients, 63%) or PA-RT (61 patients, 37%). The median follow-up time for the entire cohort was 49 (range = 5–199) months. The patients receiving adjuvant ChT and RT had significantly higher 5-year OS rates (77% vs. 33%, p < .001) and 5-year PFS rates (71% vs. 30%, p < .001) when compared to those receiving adjuvant RT alone. The patients receiving P-RT and ChT had significantly higher 5-year OS rates and 5-year PFS rates when compared to those treated with adjuvant PA-RT in the entire cohort and matched cohort. Adjuvant ChT together with RT is the strongest predictor of the OS and PFS. Prophylactic PA-RT is unnecessary, even if ChT is used together with P-RT in EC patients with pelvic lymph node metastasis. Impact statement What is already known on this subject? Local and distant recurrence risks are relatively higher in patients with stage IIIC disease, postoperative adjuvant treatment is required to reduce the recurrence risk. Adjuvant RT is a common approach for patients with locally advanced EC. Optimal target volume for RT in patients with stage IIIC EC remains controversial. We demonstrated that extended field RT is unnecessary, even if ChT is used together with pelvic RT in stage IIIC EC patients. What do the results of this study add? We demonstrated that adjuvant ChT together with RT is the strongest predictor of the OS and PFS for EC patients with pelvic lymph node metastases. Extended field RT is unnecessary, even if ChT is used together with pelvic RT in EC patients with pelvic lymph node metastases. What are the implications of these findings for clinical practice and/or further research? Although adjuvant treatment modalities are associated with improvements in survival, distant metastasis still remains the most common site of recurrence in advanced EC patients. Thus, further research is warranted to identify improved combined modality strategies to optimise the outcomes for EC patients with pelvic lymph node metastasis.

Minimally invasive surgery does not impair overall survival in stage IIIC endometrial cancer patients.

We aimed to evaluate weather survival is impaired in stage IIIC endometrial cancer patients treated with minimally invasive surgery as compared to laparotomy. We analyzed surgical data and oncologic outcome of histologically proven stage IIIC endometrial cancer patients who were treated at our institution via laparotomy or via laparoscopic surgery. All the patients underwent a systematic pelvic and para-aortic lymphadenectomy and a complete tumor resection. Perioperative morbidity and overall survival of the patients subjected to the two surgical approaches were compared. Sixty-six patients with stage IIIC endometrial cancer were identified. Of these, 15 patients were operated via laparotomy and 51 via laparoscopy. The two groups were similar with regards to median age at diagnosis, BMI, histotype, number of affected lymph nodes, and median maximal diameter of the affected lymph nodes. Patients undergoing laparoscopic surgery had fewer perioperative complications, a smaller estimated blood loss, and were subjected less frequently to transfusions. Overall survival at 60months of follow-up did not differ between the two groups. At uni- and multivariate analysis, surgical approach did not affect survival. Only age was a variable associated with overall survival. Minimally invasive surgery has better perioperative outcomes and does not impair survival in stage IIIC endometrial cancer patients. Age at diagnosis is the only factor independently affecting survival.

Role of lymphadenectomy in endometrial cancer with nonbulky lymph node metastasis: Comparison of comprehensive surgical staging and sentinel lymph node algorithm

ObjectivesTo compare survival and progression outcomes between 2 nodal assessment approaches in patients with nonbulky stage IIIC endometrial cancer (EC). MethodsPatients with stage IIIC EC treated at 2 institutions were retrospectively identified. At 1 institution, a historical series (2004–2008) was treated with systematic pelvic and para-aortic lymphadenectomy (LND cohort). At the other institution, more contemporary patients (2006–2013) were treated using a sentinel lymph node algorithm (SLN cohort). Outcomes (hazard ratios [HRs]) within the first 5 years after surgery were compared between cohorts using Cox models adjusted for type of adjuvant therapy. ResultsThe study included 104 patients (48 LND, 56 SLN). The use of chemoradiotherapy was similar in the 2 cohorts (46% LND vs 50% SLN), but the use of chemotherapy alone (19% vs 36%) or radiotherapy alone (15% vs 2%) differed. Although there was evidence of higher risk of cause-specific death (HR, 2.10; 95% CI, 0.79–5.58; P = 0.14) and lower risk of para-aortic progression (HR, 0.27; 95% CI, 0.05–1.42; P = 0.12) for the LND group, the associations did not meet statistical significance. The risk of progression was not significantly different between the groups (HR, 1.27; 95% CI, 0.60–2.67; P =0 .53). In parsimonious multivariable models, high-risk tumor characteristics and nonendometrioid type were independently associated with lower cause-specific survival and progression-free survival. ConclusionsIn EC patients with nonbulky positive lymph nodes, use of the SLN algorithm with limited nodal dissection does not compromise survival compared with LND. Aggressive pathologic features of the primary tumor are the strongest determinants of prognosis.

Removal of positive pelvic sentinel lymph nodes without additional lymphadenectomy does not compromise pelvic side wall control in patients with endometrial cancer

Objective: The aim of this study was to evaluate whether pelvic side wall (PSW) control is compromised by removal of positive sentinel lymph nodes (SLNs) alone compared with SLN and additional lymph node dissection (SLN + LND) in patients with stage IIIC1 endometrial cancer.

Adjuvant combined-modality therapy for stage IIIC endometrioid and non-endometrioid endometrial cancer

ObjectiveTo identify the optimal adjuvant treatment regimen for patients with endometrioid and non-endometrioid node-positive endometrial cancer. MethodsWe retrospectively identified 249 women with FIGO 2009 stage IIIC endometrial cancer at our institution who underwent surgical staging from 1985 to 2015 followed by external beam radiotherapy (RT), chemotherapy (CT), or a combination of CT + RT. Survival rates were calculated using the Kaplan-Meier method. ResultsThe 5-year disease-specific survival (DSS) rate for all patients was 65%. Adjuvant CT + RT conferred higher rates of 5-year DSS as compared to CT alone in patients with grade 3 endometrioid and non-endometrioid tumors (61% vs. 27%, P = 0.04 and 67% vs. 38%, P = 0.02, respectively). Among patients with non-endometrioid tumors, treatment with concurrent chemoradiotherapy followed by additional sequential chemotherapy had higher 5-year DSS rates than with concurrent chemoradiotherapy alone (74% vs. 50%, P = 0.02). The 3-year pelvic recurrence rate was 5% with RT ± CT and 35% with CT alone (P < 0.001) for all patients. No paraaortic nodal failures were observed following extended-field RT, but 14% of patients who received pelvic-only RT or CT alone developed recurrences in the paraaortic nodes (P < 0.001). ConclusionsCombined-modality therapy including adjuvant external beam pelvic radiotherapy yields excellent outcomes for patients with all subtypes of node-positive endometrial cancer. The most pronounced DSS advantage from adjuvant chemoradiotherapy was evident in women with non-endometrioid endometrial cancer.

Mucinous endometrial cancer: Clinical study of the eleven cases.

OBJECTIVE:In this study, we analyzed surgico-pathologic factors of mucinous type endometrial carcinoma and examined its frequency of recurrence.METHODS:In this study, eleven cases, definitely diagnosed as pure mucinous type endometrium carcinoma between January 1993 and May 2013, were reviewed.RESULTS:Of 1640 women with endometrium carcinoma, 11 (0.67%) of them had a mucinous cell type. Mean age of the study group was 55 years. According to the FIGO 2009, 10 (90.9%) cases were evaluated as stage I and 1 (9.1%) as stage IIIC1. The presence of lymph node metastasis was noticed in only one (12.5%) of eight patients who underwent lymphadenectomy. In this case, metastasis was detected in the pelvic lymph node. Four patients underwent adjuvant therapy as pelvic radiotherapy. Median follow-up time was 50 months (range, 5–84). Recurrence was observed in one (9.1%) patient with stage IIIC1 endometrial cancer in 30 months after primary surgery. The site of recurrence was only in the upper abdominal region.CONCLUSION:Based on our study, mucinous endometrial carcinoma has good prognostic factors, and long term survival can be achieved surgically alone in patients with stage I.

A multi-institutional analysis of sequential versus 'sandwich' adjuvant chemotherapy and radiotherapy for stage IIIC endometrial carcinoma.

ObjectiveTo analyze the outcomes of sequential or sandwich chemotherapy (ChT) and radiotherapy (RT) in patients with node-positive endometrial cancer (EC).MethodsData from 4 centers were collected retrospectively for 179 patients with stage IIIC EC treated with postoperative RT and ChT (paclitaxel and carboplatin). Patients were either treated with 6 cycles of ChT followed by RT (sequential arm; 96 patients) or with 3 cycles of ChT, RT, and an additional 3 cycles of ChT (sandwich arm; 83 patients). Prognostic factors affecting overall survival (OS) and progression-free survival (PFS) were analyzed.ResultsThe 5-year OS and PFS rates were 64% and 59%, respectively, with a median follow-up of 41 months (range, 5–167 months). The 5-year OS rates were significantly higher in the sandwich than sequential arms (74% vs. 56%; p=0.03) and the difference for 5-year PFS rates was nearly significant (65% vs. 54%; p=0.05). In univariate analysis, treatment strategy, age, International Federation of Gynecology and Obstetrics (FIGO) stage, pathology, rate of myometrial invasion, and grade were prognostic factors for OS and PFS. In multivariate analysis, non-endometrioid histology, advanced FIGO stage, and adjuvant sequential ChT and RT were negative predictors for OS, whereas only non-endometrioid histology was a prognostic factor for PFS.ConclusionPostoperative adjuvant ChT and RT for stage IIIC EC patients, either given sequentially or sandwiched, offers excellent clinical efficacy and acceptably low toxicity. Our data support the superiority of the sandwich regimen compared to the sequential strategy in stage IIIC EC patients for OS.

The Utility of Dissected Lymph Node Number and Lymph Node Metastasis Ratio In Stage IIIC Endometrium Adenocarcinoma: A Multicentric Analysis

The prognostic impact of number of dissected and metastatic lymph nodes, the lymph node metastasis ratio in stage IIIC endometrium cancer is not well-studied. Thus, the purpose of this retrospective multicentric study is to investigate the prognostic value of the number of dissected (LNC) and positive nodes (pN) with the value of the lymph node ratio (LNR) in FIGO stage IIIC endometrial cancer patient who received postoperative radiotherapy with or without chemotherapy. From January 2001 to December 2016, a total of 180 stage IIIC endometrial cancer patients who were treated with surgery and adjuvant postoperative radiotherapy (RT) (51 patients, 28%) or radiotherapy and chemotherapy (RT-CT) (129 patients, 72%) were retrospective analyzed. The LNR was defined as the number of positive lymph nodes divided by the total number of lymph nodes dissected. The endpoints were overall survival (OS) and progression-free survival (PFS). The median age and follow up times for entire cohort were 60 years (range 36 – 88 years) and 50.5 months (range 2.8 – 199.2 months), respectively. The median dissected and metastatic lymph node numbers were 36 (range 5 – 34) and 2 (range 1 – 45), respectively. The receiver-operating characteristic (ROC) analysis identified 36 [AUC=0.390 (%95CI; 0.304-0.476); p=002] as cut-off value for LNC, with 53% sensitivity and 53% specificity. For LNR, the cut-off value determined in ROC analysis was 10% [AUC=0.636 (%95CI; 0.548 – 0.725), p=0.001] with 60% sensitivity and 60% specificity. In univariate analysis, patients with an LNC ≥36 and LNR value less than 10% had better 5-year OS (68% vs 54% p=0.04; %76.0% vs.45.0%, p < 0.001 respectively), 5-year PFS rates (67% vs 48% p=0.01; 74% vs. 41%, p<0.001 respectively). Multivariate analysis only revealed that LNR was an independent prognostic factor for OS (hazard ratio [HR=2.06 (95% CI; 1.26-3.36); p=0.004) and PFS [HR=1.83 (95%CI; 1.16-2.88; p = 0.001)]. Additional analyses revealed grade I-II histology, receiving adjuvant chemotherapy showed better OS and PFS than counterpart groups (p=0.02, p<0.001 and p=0.04 and p<0.001 respectively). More than 10% LNR and high grade (grade III) histology are an important prognostic factors for OS and PFS in stage IIIC endometrial carcinoma patients. Our findings suggest that addition of chemotherapy to RT should be the preferred adjuvant treatment strategy for patients with stage IIIC endometrial cancer with higher grade disease and high lymph node metastasis ratio.

Survival Outcomes of Stage IIIC Endometrioid and Non-Endometrioid Endometrial Cancer Treated with Combined Modality Adjuvant Therapy

The optimal adjuvant treatment for stage IIIC endometrial cancer remains controversial with the recent report of GOG 258 and PORTEC-3 leading to potentially conflicting conclusions about the benefit of combined modality treatment. These randomized trials included endometrioid and non-endometrioid subsets although they are known to have different patterns of recurrence. We aimed to identify the adjuvant treatment regimen associated with the best survival outcomes for histologic subsets. Patients with clinical or pathological stage IIIC who underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and lymph node sampling between 2/1985 – 9/2015 were identified. Median follow-up time from the time of surgery for these 282 patients was 56 months (range, 2-325 months). The Kaplan-Meier method was used to calculate overall survival (OS), disease specific survival (DSS), and pelvic disease control from the time of surgery. Comparisons between patient and treatment characteristics were assessed using log-rank tests. Univariate and multivariable analyses were calculated using Cox proportional hazards modeling. Among patients with endometrioid histology (n=177), 87% received external beam radiation therapy (EBRT); the most common regimen was concurrent chemoradiation followed by adjuvant chemotherapy (34%). The majority of patients with non-endometrioid (serous, clear cell, carcinosarcoma, adenosquamous; n=105) and grade 3 (n=143) histologies received chemotherapy with or without EBRT at rates of 84% and 80%, respectively; adjuvant chemotherapy alone was utilized in 44% and 37% of patients, respectively. OS, DSS, and pelvic disease control for all patients at 5 years was 63%, 65%, and 77%. Among the grade 1/2 endometrioid subset, 5-year DSS was 80% for EBRT alone and 84% for chemoradiation (p=0.8); grade 3 endometrioid patients had rates of 58% and 66%, respectively (p=0.6). For non-endometrioid patients, 5-year DSS improved with chemoradiation (72%) as compared to chemotherapy alone (42%; p<0.02). Age >60 (HR 2.39 [95% CI 1.57-3.63], p<0.001), non-endometrioid histology (HR 2.27 [95% CI 1.22-4.23], p=0.01), grade 3 (HR 2.62 [95% CI 1.65-4.14], p<0.001), adnexal involvement (HR 1.65 [95% CI 1.08-2.50], p=0.02), and >50% myometrial invasion (HR 2.47 [95% CI 1.55-3.91], p<0.001) were independently associated with lower DSS. Pelvic failure was associated with death (HR 1.68 [95% CI 1.08-2.60], p=0.02). Patients with gross disease who received EBRT with a boost experienced a similar high rate of pelvic disease control as patients without gross disease treated with EBRT without a boost (92% vs. 90%, p=0.8). Patients with endometrioid cancer had similar outcomes if treated with EBRT with or without chemotherapy. Combined modality treatment resulted in higher rates of DSS and pelvic disease control in patients with non-endometrioid high-risk histology as compared to patients who received chemotherapy alone.

What are the Optimal Radiation Fields for FIGO IIIC Endometrial Cancer? A Multi-Institutional Study

In GOG-258, rates of pelvic & para-aortic (PA) nodal failure were lower with the addition of adjuvant radiation (RT) compared to chemotherapy alone, although details on RT fields have not yet been reported. In patients with node positive endometrial cancer, the selection of pelvic (PRT) vs. extended field RT (EFRT) has yet to be defined. This study evaluates outcomes and sites of failure in patients with FIGO stage IIIC endometrial cancer treated with PRT vs. EFRT. In a multi-institutional retrospective cohort study, we identified 143 patients with FIGO IIIC endometrioid endometrial cancer s/p surgical staging who received adjuvant RT from 1/2000-12/2016. RT fields were reviewed and categorized as EFRT if the superior field border included the renal hilum or PRT if below. Baseline characteristics & outcomes were compared by stage (IIIC1 vs. IIIC2) and RT type (PRT vs. EFRT). Actuarial estimates of RFS & OS were calculated by Kaplan-Meier & compared by logrank. Sites of failure were reported as local (vaginal), regional (pelvic or PA nodal) or distant, & within or outside the RT field. Median follow-up was 59.3 months. Clinical and treatment characteristics for 3 treatments groups are described in Table 1: pelvic node positive (IIIC1) & elective EFRT, pelvic node positive (IIIC1) & PRT, and PA node positive (IIIC2) & EFRT. Recurrence rates were lowest for patients with IIIC1 EFRT (5-year RFS 78.9%), but did not significantly differ from IIIC1 PRT (72.5%) or IIIC2 EFRT (69.3%, p =0.44). The 5-year OS rates were similar by group: 91.7% for IIIC1 EFRT, 86.5% for IIIC1 PRT, and 84.9% for IIIC2 EFRT (p=0.65). Of 31 patients with recurrence, most had distant relapse outside the RT field (16, 52%). In-field recurrences were local (3, 13%), regional (13%) or both (1, 3%). Of 78 IIIC1 patients treated with PRT, 7 patients (9%) had PA failure. Most patients with PA relapse had LVI (86%), ≥50% MMI (71%), & grade 3 disease (57%). Adjuvant RT results in excellent survival outcomes for patients with FIGO IIIC endometrial cancer. For patients with positive pelvic nodes, further study is warranted to determine if those with LVI, deep MMI & grade 3 disease benefit from EFRT.Abstract TU_21_3531; Table 1Patient CharacteristicsIIIC1 EFRTIIIC1 PRTIIIC2 EFRTp-value∗Wilcoxon rank sum, Kruskal-WallisN=32 (22.4%)N = 78 (54.5%)N = 33 (23.1%)Median Age (Range)57.5 (33-84)60.5 (41-78)57 (44-74)0.20Grade1238 (25.0)18 (56.3)6 (18.8)23 (29.5)33 (42.3)22 (28.2)11 (33.3)12 (36.4)10 (30.3)0.58LVI25 (78.1)53 (69.7)23 (71.9)0.77MMI ≥50%23 (71.9)49 (62.8)28 (84.8)0.16Gross residual diseaseInvolved LN VaginalOther01 (3.1)01 (1.3)0012 (36.4)01 (3.0)<.0001Median LNs dissected (Range)11.5 (2-46)13 (1-55)12 (0-39)0.99Median LNs involved (Range)1 (1-5)1 (1-10)3 (0-19)0.59Median EBRT dose in Gy (Range)45 (45-50.4)45 (45-56)45 (21.6-54)0.1Systemic Chemotherapy29 (92)63 (81)33 (100)∗ Wilcoxon rank sum, Kruskal-Wallis Open table in a new tab

Patterns of FIRST recurrence of stage IIIC1 endometrial cancer with no PARAAORTIC nodal assessment

ObjectiveTo assess the rates and distribution of first recurrence in patients with FIGO stage IIIC1 endometrial cancer (EC) who did not undergo paraaortic dissection at surgical staging. MethodsWe retrospectively selected all (n = 207) stage IIIC1 patients treated at a single institution from 5/1993–1/2017. Sites of first recurrence were identified, disease-free (DFS) and overall survival (OS) calculated, multivariate logistic regression performed to identify factors associated with recurrence. ResultsThree-year DFS and OS were 66.5% and 85.7%, respectively. The most common histology was endometroid (64.2%). Three-year DFS was 81% (SE±3.8%) endometrioid vs. 39.5% (SE±6.6%) non-endometrioid (P < 0.001). Three-year OS was 96.9% (SE±1.8%) endometrioid vs. 65.6% (SE±6.7%) non-endometrioid (P < 0.001). Sixty-two (30.1%) patients recurred. Patterns of recurrence were: 14 (8.3%) multiple sites, 17 (8.2%) abdominal, 14 (6.8%) extra-abdominal, 17 (8.3%) isolated nodal (8 of these (3.9%) paraaortic). Patients with isolated tumor cells (ITCs) in lymph nodes only had 12/71 (17%) recurrence rate vs. 50/135 (37%) for patients with micro−/macrometastasis. On univariate analysis, grade (HR 4.67 95%CI 1.5–14.5, P = 0.008), histology (HR 4.9 95%CI 2.6–9.3, P < 0.001), myometrial invasion (HR 1.9 95%CI 1.04–3.5, P = 0.04), pelvic washing (HR 2.2 95%CI 1.1–4.5, P = 0.03), tumor volume in pelvic LNs (ITC vs. micro−/macrometastasis; HR 0.3 95%CI 0.2–0.7, P = 0.003) were associated with recurrence. On multivariate analysis, only histology was associated with recurrence (HR 7.88 95%CI 3.43–18.13, P < 0.001). ConclusionsIsolated paraaortic recurrence in stage IIIC1 EC is uncommon. Micro−/macrometastasis were associated with twice the recurrence rate compared to ITC. These data will help clinicians counsel patients with stage IIIC1 EC regarding paraaortic assessment.

Comparison of a sentinel lymph node mapping algorithm and comprehensive lymphadenectomy in the detection of stage IIIC endometrial carcinoma at higher risk for nodal disease.

To determine if a sentinel lymph node (SLN) mapping algorithm will detect metastatic nodal disease in patients with intermediate-/high-risk endometrial carcinoma. Patients were identified and surgically staged at two collaborating institutions. The historical cohort (2004-2008) at one institution included patients undergoing complete pelvic and paraaortic lymphadenectomy to the renal veins (LND cohort). At the second institution an SLN mapping algorithm, including pathologic ultra-staging, was performed (2006-2013) (SLN cohort). Intermediate-risk was defined as endometrioid histology (any grade), ≥50% myometrial invasion; high-risk as serous or clear cell histology (any myometrial invasion). Patients with gross peritoneal disease were excluded. Isolated tumor cells, micro-metastases, and macro-metastases were considered node-positive. We identified 210 patients in the LND cohort, 202 in the SLN cohort. Nodal assessment was performed for most patients. In the intermediate-risk group, stage IIIC disease was diagnosed in 30/107 (28.0%) (LND), 29/82 (35.4%) (SLN) (P=0.28). In the high-risk group, stage IIIC disease was diagnosed in 20/103 (19.4%) (LND), 26 (21.7%) (SLN) (P=0.68). Paraaortic lymph node (LN) assessment was performed significantly more often in intermediate-/high-risk groups in the LND cohort (P<0.001). In the intermediate-risk group, paraaortic LN metastases were detected in 20/96 (20.8%) (LND) vs. 3/28 (10.7%) (SLN) (P=0.23). In the high-risk group, paraaortic LN metastases were detected in 13/82 (15.9%) (LND) and 10/56 (17.9%) (SLN) (%, P=0.76). SLN mapping algorithm provides similar detection rates of stage IIIC endometrial cancer. The SLN algorithm does not compromise overall detection compared to standard LND.

Benefit of combination chemotherapy and radiation stratified by grade of stage IIIC endometrial cancer.

The optimal strategy for adjuvant therapy in stage IIIC endometrial cancer has not been determined. Our aim was to evaluate survival benefit of different treatments and to investigate if benefit varied by histologic grade. We identified 199 patients with stage IIIC endometrial cancer from 2000 to 2012 through the Siteman Cancer Center registry. All patients underwent surgical staging followed by no adjuvant therapy (NAT), radiation (RT), chemotherapy (CT) or chemoradiation (CRT). The association between adjuvant treatment and overall survival was explored using Kaplan-Meier plots and multivariable Cox regression analysis. Multivariable analysis was stratified by low- or high-grade to explore the interaction between grade and treatment. Most patients received CRT (50.3%) followed by CT (23.1%), RT (16.1%) and NAT (10.5%). Survival after CRT was superior to NAT (p<0.001), RT (p=0.010) and CT (p<0.001). After adjusting for covariates, treatment with RT, CT and CRT led to a 57% (p=0.024), 62% (p=0.003) and 83% (p<0.001) reduction in risk of death compared to NAT, respectively. With CRT as the reference, the adjusted hazard of death was higher with NAT (5.94, p<0.001), RT (2.56, p=0.009) and CT (2.24, p=0.004). Stratifying by grade, RT and CRT led to a 67% (p=0.039) and 85% (p<0.001) reduction in death, compared to NAT in low-grade patients. CT and CRT led to a 72% (p=0.003) and 83% (p<0.001) reduction in death, compared to NAT in high-grade patients. Our findings suggest that CRT should be the preferred adjuvant treatment strategy for patients with stage IIIC endometrial cancer.

The role of para-aortic lymphadenectomy in stage IIIC endometrial cancer: A single-institute study

The therapeutic value of para-aortic lymphadenectomy (PAL) in women with endometrial cancer (EC) remains uncertain. We retrospectively analysed 25 patients with stage IIIc EC (17 stage IIIC1; 8 IIIC2) who were treated in our institution. All subjects had undergone pelvic lymphadenectomies in which para-aortic nodes were sampled, or removed only when these nodes were enlarged. Sampling of para-aortic nodes or PAL was performed in all patients with stage IIIC2 disease and one of 17 with stage IIIC1 disease. Para-aortic lymph nodes were the most frequent site of recurrence in stage IIIC1 patients, but no such recurrences occurred in stage IIIC2 patients. Overall survival tended to be shorter in stage IIIC1 patients than stage IIIC2 patients. Our findings indicate that PAL improves the outcomes of patients with EC and high risk of para-aortic lymph node metastasis, such as those with positive pelvic lymph nodes or enlargement of para-aortic lymph nodes.Impact statementPara-aortic lymph node (PALN) metastases are important prognostic factors in endometrial cancer.Overall survival of patients with stage IIIC1 disease is generally longer than for those with stage IIIC2 disease.Retrospective studies – but no prospective studies – have suggested that para-aortic lymphadenectomy (PAL) provides a survival benefit.In our institution, we had performed PAL or para-aortic sampling for patients with enlarged PALNs; therefore, as most IIIC1 patients had no enlarged PALNs, they underwent pelvic lymphadenectomy only, whereas all IIIC2 patients had enlarged PALNs and underwent pelvic lymphadenectomy and PAL or PALN sampling in addition to pelvic lymphadenectomy. However, under this policy, survival of stage IIIC1 patients was not better than for stage IIIC2 patients. Our retrospective study indicates a survival benefit for PAL in patients with pelvic node-positive or enlarged PALN. PAL warrants a prospective randomised trial to see whether it should be a standard treatment in these patients.

FIGO stage IIIC endometrial cancer identification among patients with complex atypical hyperplasia, grade 1 and 2 endometrioid endometrial cancer: laparoscopic indocyanine green sentinel lymph node mapping versus frozen section of the uterus, why get around the problem?

To compare two surgical strategies used to identify lymph node metastases in patients with preoperative diagnosis of complex atypical hyperplasia (CAH), grade 1 and 2 endometrial cancer (EC). Data on patients with preoperative diagnosis of CAH, grade 1 and 2 EC undergoing laparoscopic indocyanine green (ICG) sentinel lymph node (SLN) mapping followed by frozen section of the uterus were collected. When risk factors were identified at frozen section, patients were subjected to a systematic lymphadenectomy. False negative (FN) rates, negative predictive values (NPV), positive predictive values (PPV) and correlation with stage IIIC EC were calculated for the systematic lymphadenectomy based on frozen section of the uterus and for the SLN mapping. Six (9.5%) out of 63 patients had lymph nodal metastases. Based on frozen section of the uterus, 22 (34.9%) and 15 (22.2%) patients underwent a pelvic and a pelvic and paraaortic lymphadenectomy, respectively. Five patients with stage IIIC disease were identified with a FN rate of 16.7% and a NPV and PPV of 97.6 and 27.3%, respectively. Overall and bilateral detection rates of ICG SLN mapping were 100 and 97.6%, respectively; no FN were recorded. The identification of patients with stage IIIC disease with ICG SLN mapping showed a NPV and PPV of 100%. Correlation between indication to lymphadenectomy and stage IIIC disease was poor (κ=0.244) when based on frozen section of the uterus and excellent (κ=1) when based on SLN mapping. ICG SLN mapping reduces the number of unnecessary systematic lymphadenectomies and the risk of underdiagnosing patients with metastatic lymph nodes.

Impact of paraaortic lymphadenectomy for endometrial cancer with positive pelvic lymph nodes: A Korean Radiation Oncology Group study (KROG 13-17)

AimWe investigated the role of paraaortic lymph node dissection (PALND) in patients with stage IIIC1 endometrial carcinoma after surgery followed by adjuvant radiotherapy (RT) alone or chemoradiotherapy (CTRT). MethodsWe performed a subgroup analysis in 151 patients treated with adjuvant pelvic RT. Paraaortic-recurrence free survival, disease-free survival (DFS) and overall survival (OS) were analyzed. ResultsIn adjuvant RT alone, PALND was significantly related to reduced risk of paraaortic recurrence (0% vs. 17.1%) and distant metastasis (4.5% vs. 19.5%) compared with the no PALND group. PALND affected 5-year DFS (90.2% vs. 58.9%, p = 0.016) and OS (100% vs. 83.1%, p = 0.022). For the CTRT group, the paraaortic recurrence rate was 19.5% for the no PALND group and 12.8% for the PALND group (p = 0.682). Of patients who underwent PALND in the CTRT group, less extensive PALND was significantly related to increased paraaortic recurrence (≤10 vs. >10 dissected LNs, 17.1% vs. 0%). In the no PALND group (n = 82), 5-year paraaortic-recurrence free survival was 79.4% for the CTRT group and 76.2% for the RT alone group (p = 0.941). In multivariate analysis, PALND was significantly associated with reduced risk of disease-specific death (HR, 0.50; 95% CI, 0.26–0.96; p = 0.037). ConclusionPALND provided excellent paraaortic control and improved outcome in stage IIIC1 endometrial cancer with favorable tumor features treated with adjuvant RT alone. Less extensive PALND was associated with significantly increased paraaortic recurrence in patients with advanced tumor features treated with adjuvant CTRT. Combined CTRT did not affect disease control in the paraaortic region compared with RT alone.