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Objectives: To assess associations between treatment and recurrence-free survival (RFS) among patients with isolated tumor cells (ITCs) in sentinel lymph nodes (SLN) and otherwise stage I/II endometrioid endometrial cancer (EC)., Methods: A multi-institutional retrospective study of patients with SLN ITCs (<200 cells and < 0.2 mm) was performed. Only patients with otherwise stage I/II EC, endometrioid histology, and no evidence of micro-or macrometastases were included. Univariate and multivariable Cox proportional hazard models were used to evaluate associations between treatment, tumor characteristics, and RFS., Results: 175 patients were included. Median follow up time was 31 months. 39% stage IB and 12% stage II disease. 76 (43%) received no adjuvant therapy or vaginal brachytherapy only (NAT/VBT), 21 (12%) had external beam radiation (EBRT), and 78 (45%) received chemotherapy +/- radiation. Patients who received chemotherapy more often had tumors with deep myoinvasion, lymphovascular space invasion (LVSI), and higher grade. Nine (5.1%) patients recurred; 5 distant, 3 retroperitoneal, and 1 vaginal. Extra-vaginal recurrences were similar in patients with or without chemotherapy (5.2% vs 3.8%, p = 0.68). After controlling for stage, LVSI and grade, chemotherapy and EBRT were not associated with RFS (HR = 0.63, 95%CI 0.11-3.52, and HR = 0.90, 95%CI 0.22-3.61, respectively). Type of lymph node dissection and ITC detection method were not associated with RFS., Conclusions: Risk of retroperitoneal and/or distant recurrence is low (4.6%) for patients with stage I/II endometrioid EC and ITCs in SLNs regardless of treatment. Our preliminary data suggests that adjuvant therapy may not be significantly associated with RFS. However, longer follow-up time and a larger sample size are needed before definitive recommendations regarding adjuvant therapy for patients with EC and only ITCs in SLN can be made., Competing Interests: Declaration of Competing Interest Dr. Leitao reports personal fees from JnJ/Ethicon, outside the submitted work; and Dr. Leitao is an ad hoc speaker for Intuitive Surgical, Inc. Dr. Abu-Rustum reports grants from GRAIL, grants from Stryker, outside the submitted work. Dr. Backes reports grants and personal fees from Eisai, grants and personal fees from Merck, grants from Immunogen, grants and personal fees from Clovis, personal fees from Agenus, personal fees from AstraZeneca, personal fees from Genentech, personal fees from GlaxoSmithKline, all outside the submitted work. None of the other authors have a significant conflict of interest related to the current study. Some of the investigators (Felix, Abu-Rustum, Leitao) receive grants for other projects that fund part of their time., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: According to the updated FIGO system, positive peritoneal cytology does not affect endometrial cancer stage. This revision may reduce rates of obtaining cytology, with unclear implications in advanced disease. This study evaluates the significance of positive cytology in stage III (FIGO 2009) endometrial cancer., Methods: Eligible patients received treatment for stage III endometrial cancer at a single institution and had peritoneal cytology performed., Results: Of 196 patients, 58% were ≥ 60 years old, 48% had deep myometrial invasion, 71% lymphovascular invasion, 25% cervical invasion, 37% adnexal involvement, 79% nodal involvement, and 46% aggressive histology. Positive cytology was present in 23% (45/196) and significantly associated with cervical stromal invasion, adnexal involvement, and aggressive histology (P ≤ 0.03). There was no significant difference in rates of lymphadenectomy, chemotherapy, or radiation between negative and positive cytology groups. At a median follow-up of 47 months, the 5-year freedom from relapse was 39% for positive cytology vs. 69% for negative, disease-specific survival 42% vs. 77%, and overall survival 34% vs. 72% (P < 0.001). Positive cytology correlated with higher recurrence rates in the para-aortic nodes and peritoneum (30% vs. 9%, 23% vs. 4%; P ≤ 0.008). When controlling for adverse features including aggressive histology, positive cytology was associated with an increased hazard for relapse (HR 2.3; P = 0.002) and death (HR 2.9; P < 0.001)., Conclusions: In stage III endometrial cancer, positive cytology independently predicts outcome and is associated with distinct relapse patterns. Obtaining peritoneal cytology in stage III endometrial cancer is critical., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To determine whether the frequency of cases diagnosed with stage IIIC endometrial cancer is affected by the incorporation of a modified surgical lymph node assessment., Methods: Since 2008, we have increasingly utilized a modified nodal assessment using an algorithm that incorporates SLN mapping. For this analysis, we identified all cases of newly diagnosed endometrial cancers undergoing a minimally invasive staging procedure not requiring conversion to laparotomy from 1/1/08 to 12/31/10. Procedures were categorized as standard, modified, and hysterectomy only. Differences were based on time period: 2008 (Y1), 2009 (Y2), and 2010 (Y3). Appropriate statistical tests were used., Results: We identified a total of 507 cases. The distribution of cases was 143 (Y1), 190 (Y2), and 174 (Y3). Tumor grade (P=0.05) and high-risk histologies (P=0.8) did not differ during the 3 time periods. A standard staging procedure was performed in the following cases: Y1 (93/143; 65%), Y2 (66/166; 35%), and Y3 (40/164; 23%) (P<0.001). Median operative times were as follows: Y1 (218 min), Y2 (198 min), and Y3 (176.5 min) (P<0.001). The median numbers of total lymph nodes removed among cases with at least 1 node retrieved were: Y1 (20); Y2 (10); Y3 (7) (P<0.001). Cases diagnosed as stage IIIC were as follows: Y1 (10/143; 7%), Y2 (15/166; 7.9%), and Y3 (13/164; 7.5%) (P=1.0)., Conclusions: The incorporation of a modified staging approach utilizing the SLN mapping algorithm reduces the need for standard lymphadenectomy and does not appear to adversely affect the rate of stage IIIC detection., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The hereditary basis of endometrial cancer is apparent in young women with endometrial cancer. The objective of this study was to examine risk factors and outcomes in patients 40 years of age and younger with endometrial cancer., Methods: We performed a retrospective cohort study of patients aged 40 years or less who were diagnosed with endometrial carcinoma between 1/93 and 5/08. Clinical and pathologic data were extracted from medical records. Paraffin-embedded slides from hysterectomy specimens were obtained and DNA mismatch repair (MMR) immunohistochemistry was performed. Cases were analyzed according to the presence of DNA MMR protein defects. Standard two-sided statistical tests were performed., Results: Of the 56 identified patients, the median age was 36 years (range, 24-40). The majority of the endometrial carcinomas were of endometrioid histology (91%), stage I (71%), and FIGO grade 1 (59%). Abnormal DNA MMR was found in 9 cases (16%). Cases with abnormal DNA MMR had lower body mass index (BMI) (P=0.05), and had a family history suggestive of Lynch syndrome (P=0.001). Tumors were more likely to have advanced stage disease (P<0.001), be high grade (P<0.001), have deep myometrial invasion (P<0.001), and have lymphovascular invasion (P=0.002). Cases with abnormal DNA MMR had significantly worse overall survival (P=0.028) and progression-free survival (P=0.042)., Conclusions: Endometrial cancer is rare in women aged 40 years or less. In this group of patients, loss of DNA MMR was associated with lower BMI, worse clinicopathologic factors, and worse outcome. These results may have implications when young women diagnosed with endometrial cancer are counseled regarding prognosis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To compare the incidence of metastatic cancer cells in sentinel lymph nodes (SLN) vs. non-sentinel nodes in patients who had lymphatic mapping for endometrial cancer and to determine the contribution of metastases detected on ultrastaging to the overall nodal metastasis rate., Methods: All patients who underwent lymphatic mapping for endometrial cancer were reviewed. Cervical injection of blue dye was used in all cases. Sentinel nodes were examined by routine hematoxylin and eosin (H&E), and if negative, by standardized institutional pathology protocol that included additional sections and immunohistochemistry (IHC)., Results: Between 09/2005 and 03/2010, 266 patients with endometrial cancer underwent lymphatic mapping. Sentinel node identification was successful in 223 (84%) cases. Positive nodes were diagnosed in 32/266 (12%) patients. Of those, 8/266 patients (3%) had the metastasis detected only by additional section or IHC as part of SLN ultrastaging. Excluding the 8 cases with positive SLN on ultrastaging only, 24/801 (2.99%) SLN and 30/2698 (1.11%) non-SLN were positive for metastatic disease (p=0.0003)., Conclusion: Using a cervical injection for mapping, metastatic cells from endometrial cancer are three times as likely to be detected in SLN than in the non-sentinel nodes. This finding strongly supports the concept of lymphatic mapping in endometrial cancer to fine tune the nodal dissection topography. By adding SLN mapping to our current surgical staging procedures we may increase the likelihood of detecting metastatic cancer cells in regional lymph nodes. An additional benefit of incorporating pathologic ultrastaging of SLN is the detection of micrometastasis, which may be the only evidence of extrauterine spread., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: Traditionally we have relied mainly on final FIGO stage to estimate overall oncologic outcome in endometrial cancer patients. However, it is well known that other patient factors may play equally important roles in outcome. Our objective was to develop a clinically useful nomogram in the hope of providing a more individualized and accurate estimation of overall survival (OS) following primary therapy., Methods: Using a prospectively maintained endometrial cancer database, 1735 patients treated between 1993 and 2008 were analyzed. Characteristics known to predict OS were collected. For each patient, points were assigned to each of these 5 variables. A total score was calculated. The association between each predictor and the outcome was assessed by multivariable modeling. The corresponding 3-year OS probabilities were then determined from the nomogram., Results: The median age was 62 years (range, 25-96). Final grade included: G1 (471), G2 (622), G3 (634), and missing (8). Stage included: IA (501), IB (590), IC (141), IIA (36), IIB (75), IIIA (116), IIIB (6), IIIC (135), IVA (7), and IVB (128). Histology included: adenocarcinoma (1376), carcinosarcoma (100), clear cell (62), and serous (197). Median follow-up for survivors was 29.2 months (0-162.2 months). Concordance probability estimator for the nomogram is 0.746+/-0.011., Conclusion: We developed a nomogram based on 5 easily available clinical characteristics to predict OS with a high concordance probability. This nomogram incorporates other individualized patient variables beyond FIGO stage to more accurately predict outcome. This new tool may be useful to clinicians in assessing patient risk when deciding on follow-up strategies.

The objective of this study was to review available literature pertaining to lymphatic mapping in endometrial cancer. We reviewed all published series of lymphatic mapping in endometrial cancer available through a PubMed search. Techniques used for identification of sentinel lymph nodes fell into three main categories in relation to the site of injection: 1) uterine subserosal, 2) cervical, and 3) endometrial via hysteroscopy. High detection rates may be achieved in all three categories. The use of both radiolabeled technetium and blue dye has been reported. A combination of cervical and uterine corpus injections appears feasible and less technically demanding than hysteroscopic injections. Immunohistochemistry staining of sentinel nodes coupled with step-serial section may improve the detection of micrometastasis in sentinel nodes. Meaningful sensitivity and false-negative rates cannot be calculated from current series due to their small numbers. The role of lymphatic mapping in endometrial carcinoma and the optimal injection site remains to be determined. A combination of cervical and uterine fundal injections may result in acceptable detection rates. Large-scale validation trials requiring complete pelvic and para-aortic lymphadenectomy are needed to evaluate its role in future clinical practice.

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.