Primary Surgery For Endometrial Cancer Research Articles

Locoregional Control Following Adjuvant Chemotherapy and Radiotherapy for Treatment of High-Risk Endometrial Cancer

<h3>Purpose/Objective(s)</h3> Patients with locally advanced stage and aggressive histology endometrial cancer are at high risk of relapse, and usually treatment includes surgery, chemotherapy and radiotherapy. The timing and coordination of chemotherapy and radiotherapy remain controversial, though historically we have delivered adjuvant radiotherapy after completion of chemotherapy. The premise being to avoid delaying chemotherapy, which confers an overall survival benefit. We decided to review oncologic outcomes and patterns of recurrence among our patients and compare them with the published literature. <h3>Materials/Methods</h3> A retrospective review was conducted to evaluate patients who underwent primary surgery for endometrial cancer between 2005 and 2017, had a final pathology demonstrating Stage I-II endometrial cancer of serous or clear cell histology, Stage III endometrial cancer of any histology or Stage IV endometrial cancer of endometrioid adenocarcinoma histology, and were considered appropriate for adjuvant chemotherapy and radiotherapy. Kaplan-Meier analysis was used to calculate progression-free survival (PFS) and overall survival (OS). <h3>Results</h3> A total of 140 patients met the eligibility criteria and were included, with a median age of 65. The distribution according to stage was as follows: 41 (29.3%) Stage I, 24 (17.1%) Stage II, 68 (48.6%) Stage III, and 7 (5.0%) Stage IV. Of these patients, 52 (37.1%) had endometrioid, 75 (53.6%) had serous, and 11 (7.9%) had clear cell histology. All patients received chemotherapy with the median start time being 49 days after initial surgery. In total, 120 (92%) completed 6 cycles of chemotherapy. The median start time for radiotherapy was 35 days after chemotherapy and 192 days after surgery, with 129 (92.1%) completing adjuvant radiotherapy. The median dose of external beam radiotherapy (EBRT) was 4500 cGy in 25 fractions and the median dose of vaginal brachytherapy, when used, was 1800 cGy in 3 fractions. In terms of EBRT technique, 54 were treated with traditional conformal fields and 74 with IMRT techniques. The median follow-up was 63.9 months and the 5-year PFS and OS rates were 69% and 66% respectively. A total of 42 patients (30.0%) developed a recurrence; of which 2 (1.4%) were local, 10 (7.1%) were locoregional (any with component of locoregional failure), 8 (5.7%) were isolated para-aortic and 27 (19.3%) were distant. Among the 129 patients receiving radiotherapy, 6 (4.6%) patients had locoregional failure. Only 7 (5.4%) of patients had an "in-field" recurrence after EBRT, with 4 (3.1%) among patients treated with conformal fields and 3 (2.3%) among those treated with IMRT. <h3>Conclusion</h3> Adjuvant radiotherapy given after completion of surgery and adjuvant chemotherapy leads to favorable outcomes with regards to PFS and OS (compared to published randomized studies), and still results in excellent locoregional control.

Sentinel lymph node biopsy in early stage endometrial cancer: a Turkish gynecologic oncology group study (TRSGO-SLN-001)

ObjectiveThe aim of this multicenter study was to evaluate the feasibility of sentinel lymph node (SLN) mapping in clinically uterine confined endometrial cancer.MethodsPatients who underwent primary surgery for endometrial cancer...

Patient-reported outcomes after surgery for endometrial carcinoma: Prevalence of lower-extremity lymphedema after sentinel lymph node mapping versus lymphadenectomy

ObjectiveTo compare the prevalence of patient-reported lower-extremity lymphedema (LEL) with sentinel lymph node (SLN) mapping versus comprehensive lymph node dissection (LND) for the surgical management of newly diagnosed endometrial carcinoma. MethodsPatients who underwent primary surgery for endometrial cancer from 01/2006-12/2012 were mailed a survey that included a validated 13-item LEL screening questionnaire in 08/2016. Patients diagnosed with LEL prior to surgery and those who answered ≤6 survey items were excluded. ResultsOf 1275 potential participants, 623 (49%) responded to the survey and 599 were evaluable (180 SLN, 352 LND, 67 hysterectomy alone). Median BMI was similar among cohorts (P = 0.99). External-beam radiation therapy (EBRT) was used in 10/180 (5.5%) SLN and 35/352 (10%) LND patients (P = 0.1). Self-reported LEL prevalence was 27% (49/180) and 41% (144/352), respectively (OR, 1.85; 95% CI, 1.25–2.74; P = 0.002). LEL prevalence was 51% (23/45) in patients who received EBRT and 35% (170/487) in those who did not (OR, 1.95; 95% CI, 1.06–3.6; P = 0.03). High BMI was associated with increased prevalence of LEL (OR, 1.04; 95% CI, 1.02–1.06; P = 0.001). After controlling for EBRT and BMI, LND retained independent association with an increased prevalence of LEL over SLN (OR, 1.8; 95% CI, 1.22–2.69; P = 0.003). Patients with self-reported LEL had significantly worse QOL compared to those without self-reported LEL. ConclusionsThis is the first study to assess patient-reported LEL after SLN mapping for endometrial cancer. SLN mapping was independently associated with a significantly lower prevalence of patient-reported LEL. High BMI and adjuvant EBRT were associated with an increased prevalence of patient-reported LEL.

Risk-based stratification of carcinomas concurrently involving the endometrium and ovary

ObjectiveDetermining whether carcinomas concurrently involving endometrium and ovary are independent primary tumors (IPTs) or endometrial carcinomas with ovarian metastases (at least stage IIIA endometrial cancers, IIIA-EC) using clinicopathologic criteria is often challenging. Recent genomic studies showed that most such tumors are clonally related. We sought to identify clinicopathologic features associated with clinical outcomes, and to separate women with these tumors into clinically low-risk and high-risk groups. MethodsWe reviewed clinical and pathologic data from 74 women who, between 1993 and 2014, underwent primary surgery for endometrial cancer and had concurrent ovarian involvement. ResultsThe endometrial carcinomas were endometrioid (EECs, n = 41) or non-endometrioid (ENECs, n = 33). Nineteen (26%) cases were originally classified as IPTs using clinicopathologic criteria. Multivariate analysis revealed that lymph node involvement (hazard ratio (HR) = 2.38, 95% CI 1.13–5.02, p = 0.023) and non-endometrioid endometrial tumor histology (HR = 6.27, 95% CI 2.6–15.13, p < 0.001) were associated with poorer progression-free survival (PFS). Multivariate analysis of 65 women with known lymph node status revealed two prognostically distinct groups: a high-risk group comprising ENECs with ≥50% myometrial invasion irrespective of lymph node status (n = 21; median PFS 12.7 months, 95% CI, 9.24–19.8); and a low-risk group consisting of all EECs, as well as lymph node-negative ENECs with <50% myometrial invasion (n = 44, median PFS not reached). The risk-based classification was superior to the original classification of endometrial cancers as IPTs vs. IIIA-EC for predicting PFS (log-rank test, p < 0.001 vs. p = 0.07). ConclusionOur proposed risk-based stratification enables categorization of women with concurrent endometrial and ovarian tumors according to their likely clinical outcomes.

The Clinical Features of Recurrent Endometrial Cancer in Japan: Chemotherapy Instead of Radiotherapy as Postoperative Adjuvant Treatment.

Chemotherapy is a standard adjuvant treatment after primary surgery for endometrial cancer in Japan. We aimed to characterize the clinical features of recurrent endometrial cancer (REC) patients in Japan. We retrospectively reviewed the medical records of 112 REC patients who were primarily treated at 1 of 3 university hospitals in Japan from 2005 to 2012. We analyzed overall survival since the first recurrence (R-OS) in accordance with several factors. Median patient age was 64 years. The median follow-up period was 48 months. The distributions of cancer stage and histological subtype lacked distinctive features, and most patients had a high risk for recurrence at the time of the primary surgery. Although approximately 78% of patients received adjuvant chemotherapy, 85/112 patients (76%) experienced recurrence within 2 years after the initial treatment ended. For patients receiving adjuvant chemotherapy, regional lymph node (LN) and distant-site recurrence were more frequent (>40%) than vaginal or intra-abdominal recurrence. Median survival and 5-year R-OS were 27 months and 26.1%, respectively. The R-OS was significantly better for patients aged 65 years or older, those with negative peritoneal cytology at the time of primary surgery, those with recurrence within regional LN (eg, pelvic LN or para-aortic LN under the renal vein) and/or vagina, and those who underwent surgery and/or radiotherapy after recurrence. A multivariate analysis indicated that positive peritoneal cytology, a disease-free interval of less than 12 months, recurrent lesions in 2 or 3 areas, and treatment excluding surgery or radiotherapy were independent predictors of poor prognosis after recurrence. Adjuvant chemotherapy was insufficient to reduce the incidence of distant recurrence. The prognosis of patients recurred within regional LN and/or vagina was significantly better than that of patients with recurrence in other lesions because of treatment with surgery and/or radiotherapy. The disease-free interval was a significant prognostic factor for REC patients.

The effect of obesity on clinical and economic outcomes in robotic endometrial cancer surgery.

The aim of this study was to compare the financial and clinical outcomes in robotic-assisted laparoscopic surgery for primary endometrial cancer between obese and nonobese women. The hospital finance department assessed the total admission costs for robotic surgery for endometrial cancer in 54 women. This included a subanalysis for costs over nine areas (ward and clinics, drugs and pharmacy, medical staff, theaters, blood products, imaging, pathology, rehabilitation therapy, and high dependency costs). Furthermore, a prospective collection of morbidity and surgical outcome data was performed. The study group included 21 nonobese and 33 obese women (body mass index >30). Obese women were more likely to stay for more than one night in hospital (20/33 [60.6%] compared to 4/21 [19.0%], P=0.032) and to have high dependency care (25/33 [75.8%] compared to 10/21 [47.6%], P=0.032). Theater time was on average 35 min longer (95% confidence interval [CI] 5–65 min, P=0.0252). Both the groups were comparable for comorbidities except for the presence of diabetes being present in the obese group (13/33 [39.4%] compared to 0/21 [0.0%], P=0.007). There were six Clavien-Dindo grade II complications in the obese group and two in the nonobese group. The average overall costs were £1,852 greater (95% CI £431–£3,277, P=0.012) in the obese group. Diabetes and hypertension were associated with increased costs, but obesity was the only independent variable. In conclusion, greater resource should be allocated to obese women undergoing primary surgery for endometrial cancer.

The Added Value of SPECT/CT in Sentinel Lymph Nodes Mapping for Endometrial Carcinoma.

This study was designed to evaluate the detection rate (DR) and sensitivity of sentinel lymph node (SLN) mapping in patients with endometrial cancer using TC99m colloid and blue dye and to evaluate the contribution of preoperative planar lymphoscintigraphy (PLSG) and SPECT/CT. A retrospective analysis of patients who underwent SLN mapping as part of their primary surgery for endometrial cancer. Patients underwent preoperative PLSG and later with additional SPECT/CT. Intraoperative detection was performed using TC99m colloid and blue dye by cervical injections. SLNs were sent separately for pathologic evaluation with ultrastaging. Fifty-three patients were included in this study. Successful preoperative mapping was achieved in 31 of 37 patients (84 %) who underwent SPECT/CT compared with only 30 of 45 patients (67 %) who underwent PLSG. SPECT/CT localizations of SLNs were anatomically accurate in 91 % of cases. Intraoperative DR of at least one SLN was 77 %, whilst the bilateral DR was 49 %. DR was significantly better using combined blue dye and TC99m colloid injections compared with blue dye alone: 81 versus 57 % for unilateral and 54 versus 28 % for bilateral mapping (P = 0.01, 0.009, respectively). Six cases of nodal metastasis were diagnosed: four by positive SLNs, and two cases were diagnosed using side-specific full dissection according to the SLN algorithm when SLN detection failed. There were no cases of false-negative results. SLN detection using cervical injections of TC99m colloid and blue dye is feasible and sensitive for patients with endometrial cancer. SPECT/CT aids to accurate locating of the SLN.

Improving sentinel lymph node detection rates in endometrial cancer: How many cases are needed?

Objective To describe sentinel lymph node (SLN) detection rates in endometrial cancer and estimate how many cases are needed to achieve > 90% SLN detection. Methods We conducted a prospective study of patients undergoing primary surgery for endometrial cancer between September 2005 and March 2009. Lymph node mapping was performed using blue dye injection into the cervix in all cases. Additional injection methods included blue dye injection in the uterine fundus, and cervical injection of Tc99m. SLNs were identified and removed, followed by regional lymph node dissection. The results were analyzed according to two study periods: an “early” phase (September 2005–December 2007) and a “late” phase (January 2008–March 2009). Results One hundred and fifteen patients with endometrial cancer were included. The cervix was the only site of injection in 82 cases (71%), while a combined cervical and fundal injection was performed in 33 cases (29%). Overall, SLN detection was achieved in 98 (85%) cases. In the initial 27 months of the study, a SLN was identified in 50 of 64 cases (78%), with 2 false negative cases. In the subsequent 15 months, successful mapping was achieved in 48 of 51 cases (94%) with no false negative cases. When examining an individual provider's performance, after the first 30 cases, the rate of successful mapping significantly increased from 77% to 94% ( P = 0.033). Conclusion Sentinel node mapping in uterine cancer requires a dedicated effort to achieve high detection rates. Surgeons should determine their individual detection rates and false negative rates. Our data demonstrate that high SLN detection rates can be achieved in women with uterine cancer and increasing surgical volume (30 cases) is associated with significantly increased detection rates.

The incidence of pelvic lymph node metastasis by FIGO staging for patients with adequately surgically staged endometrial adenocarcinoma of endometrioid histology

The seminal Gynecologic Oncology Group study on surgical pathologic spread patterns of endometrial cancer demonstrated the risk of pelvic lymph node metastasis for clinical stage I endometrial cancer based on tumor grade and thirds of myometrial invasion. However, the FIGO staging system assigns surgical stage by categorizing depth of myometrial invasion in halves. The objective of this study was to determine the incidence of pelvic lymph node metastasis in endometrial cancer based on tumor grade and myometrial invasion as per the current FIGO staging system. We reviewed the records of all patients who underwent primary surgical staging for clinical stage I endometrial cancer at our institution between May 1993 and November 2005. To make the study cohort as homogeneous as possible, we included only cases of endometrioid histology. We also included only patients who had adequate staging, which was defined as a total hysterectomy with removal of at least eight pelvic lymph nodes. During the study period, 1036 patients underwent primary surgery for endometrial cancer. The study cohort was composed of the 349 patients who met study inclusion criteria. Distribution of tumor grade was as follows: grade 1, 80 (23%); grade 2, 182 (52%); and grade 3, 87 (25%). Overall, 30 patients (9%) had pelvic lymph node metastasis. The incidence of pelvic lymph node metastasis in relation to tumor grade and depth of myometrial invasion (none, inner half, and outer half) was as follows: grade 1-0%, 0%, and 0%, respectively; grade 2-4%, 10%, and 17%, respectively; and grade 3-0%, 7%, and 28%, respectively. We determined the incidence of pelvic nodal metastasis in a large cohort of endometrial cancer patients of uniform histologic subtype in relation to tumor grade and a one-half myometrial invasion cutoff. These data are more applicable to current surgical practice than the previously described one-third myometrial invasion cutoff results.

Treatment results of endometrial carcinoma with positive peritoneal washing, adnexal involvement and serosal involvement.

To review the treatment results of patients with endometrial carcinoma having positive peritoneal washing (PPW), adnexal involvement, uterine serosal involvement, or all three. The treatment records of patients who had undergone primary surgery for endometrial cancer without distant metastasis during 1990--2001 at the Department of Clinical Oncology, Tuen Mun Hospital, Hong Kong, were reviewed. Thirty-five patients were found to have involvement of positive PPW, adnexal involvement, uterine serosal involvement, or all three. Seven (20%) of them had gross or microscopic lymph-node metastasis. Thirty-three (94.3%) patients received adjuvant radiotherapy (28 whole-pelvic irradiation [WPI]; five abdominal radiotherapy [WART]). Two patients with solitary ovarian metastasis received chemotherapy, and one with isolated PPW also received adjuvant hormonal therapy. The median follow-up was 50.4 months (range 2.4-151.2 months). Multivariate analysis was carried out using the Cox regression proportional hazards model. Among the 28 patients with clinical or pathological node-negative disease (International Federation of Gynecology and Obstetrics [FIGO] stage IIIA), only two patients with solitary ovarian metastases developed recurrence. The 5-year actuarial disease-free survival (DFS) rates for the whole group and patients without lymph-node involvement were 77.9% and 91.7%, respectively. Five out of the seven patients with lymph-node involvement developed recurrences. Univariate analysis showed that lymph-node involvement (P < 0.0001) and high-grade disease (P = 0.011) were the significant poor prognostic factors. Multivariate analysis showed that lymph-node involvement was the only significant poor prognostic factor to predict poor 5-year DFS (P = 0.0001). Only one patient (3.7%) who had received WART developed grade 4 toxicity. This study showed that good treatment results could be obtained from patients with stage IIIA endometrial carcinoma without clinical or pathological lymph-node involvement after adjuvant radiotherapy, with acceptable late side-effects. The relative prognostic importance of individual IIIA involvement and the optimal adjuvant treatment remain to be determined.

Outcomes of endometrial cancer patients undergoing surgery with gynecologic oncology involvement

OBJECTIVE:This study was undertaken to compare the outcomes of patients with endometrial cancer who had primary surgery with gynecologic oncology involvement at university or community hospitals.METHODS:The study population consisted of all patients who had primary surgery for endometrial cancer with involvement of the attending physicians of the Division of Gynecologic Oncology. The patients were divided into two groups based on whether their surgery was performed at a university or community hospital. Demographic and clinical data were abstracted from the medical records.RESULTS:There were no significant differences between the two groups with regard to Quetelet index (kg/m2); intervals between biopsy and consultation, consultation and surgery, and biopsy and surgery; estimated blood loss; incidence of operative or hospital complications; frequency of appropriate surgical staging; stage distribution; histology or grade; and hospital stay. Patients at a university hospital were significantly older, had a higher severity index, were more likely to have had a vaginal hysterectomy, and participate in a research protocol. Both the Quetelet index and the severity index were significantly higher for patients who had vaginal hysterectomy than for those who had either laparoscopically assisted vaginal hysterectomy or total abdominal hysterectomy. When analyzed by surgical approach, the frequencies of pelvic and paraaortic lymph node sampling were comparable between the groups. Both the Quetelet and severity indices were significantly higher for patients who did not have lymph node sampling.CONCLUSION:Involvement of a gynecologic oncologist at the time of primary surgery for endometrial cancer was associated with comparable outcomes in both the university and community hospital setting.

Outcome of Endometrial Carcinoma Patients with Involvement of the Uterine Serosa

Objective. The goal of this work was to evaluate the outcome of endometrial carcinoma patients undergoing primary surgery who have serosal involvement (SI).Methods. Between 1980 and 1998, 562 women underwent primary surgery for endometrial cancer at the University of Chicago. Thirty-nine were noted to have SI. FIGO stages were IIIA (19), IIIB (1), IIIC (7), and IV (12). Of the 19 IIIA patients, 15 had solitary SI. Twenty-six patients received pelvic radiation therapy (RT) with or without vaginal brachytherapy (VB). One patient received whole-abdomen radiation therapy, and 13, adjuvant chemotherapy. Solitary SI patients received pelvic RT with or without VB as their sole adjuvant therapy. Disease-free survivals (DFSs) were estimated using the method of Kaplan and Meier and prognostic factors were analyzed by the log-rank test.Results. With a median follow-up of 30.3 months, the 5-year actuarial DFS of the entire group was 28.9%. Factors correlated with disease recurrence included tumor stage (P = 0.003) and lymph node involvement (P = 0.04). In addition, patients with solitary SI had a better 5-year DFS (41.5% vs 20%, P = 0.04) than patients with SI plus other extrauterine sites. Relapse occurred in 23 women overall and in 7 of 15 solitary SI patients. The most common site of disease recurrence was distant both in the entire group and in the solitary SI patients. While abdominal recurrences were common in the entire group, they were infrequent in solitary SI patients.Conclusion. Endometrial carcinoma patients with SI have a high rate of relapse and a poor outcome. Even when patients have extrauterine disease limited to SI, the outcome is relatively unfavorable. Nonetheless, our results demonstrate the need to distinguish patients with solitary SI and those with SI plus other extrauterine disease sites.

Progestagens for endometrial cancer.

Progestagen therapy following primary surgery for endometrial cancer has been advocated to reduce the risk of recurrence. The objective of this review was to assess the effect of adjuvant progestagen therapy in endometrial cancer. We searched the Cochrane Gynaecological Cancer Group trials register and MEDLINE up to May 1999. Randomised trials of progestagen therapy in women who have had surgery for endometrial cancer. Trial quality was assessed and two reviewers abstracted data independently. Six trials involving 4351 women were identified. Three trials included women with stage one disease only, whereas three included women with more advanced disease. Based on five trials, overall survival was not improved by adjuvant progestagen therapy (OR 1.05, 95% CI 0.88 to 1.24). Endometrial cancer deaths and relapse of disease appears to be reduced by progestagen therapy OR 0.88 95% CI (0.71-1.1) and 0. 81 95% CI (0.65-1.01) respectively. However, non-endometrial cancer related deaths were more common in women treated with progestagens OR 1.33 (1.02-1.73). Current evidence does not support the use of adjuvant progestagen therapy in the primary treatment of endometrial cancer.