Comparison of a sentinel lymph node and a selective lymphadenectomy algorithm in patients with endometrioid endometrial carcinoma and limited myometrial invasion.

To assess clinicopathologic outcomes between two nodal assessment approaches in patients with endometrioid endometrial carcinoma and limited myoinvasion. Patients with endometrial cancer at two institutions were reviewed. At one institution, a complete pelvic and para-aortic lymphadenectomy to the renal veins was performed in select cases deemed at risk for nodal metastasis due to grade 3 cancer and/or primary tumor diameter>2cm (LND cohort). This is a historic approach at this institution. At the other institution, a sentinel lymph node mapping algorithm was used per institutional protocol (SLN cohort). Low risk was defined as endometrioid adenocarcinoma with myometrial invasion <50%. Macrometastasis, micrometastasis, and isolated tumor cells were all considered node-positive. Of 1135 cases identified, 642 (57%) were managed with an SLN approach and 493 (43%) with an LND approach. Pelvic nodes (PLNs) were removed in 93% and 58% of patients, respectively (P<0.001); para-aortic nodes (PANs) were removed in 14.5% and 50% of patients, respectively (P<0.001). Median number of PLNs removed was 6 and 34, respectively; median number of PANs removed was 5 and 16, respectively (both P<0.001). Metastasis to PLNs was detected in 5.1% and 2.6% of patients, respectively (P=0.03), and to PANs in 0.8% and 1.0%, respectively (P=0.75). The 3-year disease-free survival rates were 94.9% (95% CI, 92.4-97.5) and 96.8% (95% CI, 95.2-98.5), respectively. Our findings support the use of either strategy for endometrial cancer staging, with no apparent detriment in adhering to the SLN algorithm. The clinical significance of disease detected on ultrastaging and the role of adjuvant therapy is yet to be determined.

Zahl Eriksson AG ，Ducie J ，Ali N ，McGree ME ，Weaver AL ，Bogani G ，Cliby WA ，Dowdy SC ，Bakkum-Gamez JN ，Abu-Rustum NR ，Mariani A ，Leitao MM Jr ... -  《-》

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.

Ducie JA ，Eriksson AGZ ，Ali N ，McGree ME ，Weaver AL ，Bogani G ，Cliby WA ，Dowdy SC ，Bakkum-Gamez JN ，Soslow RA ，Keeney GL ，Abu-Rustum NR ，Mariani A ，Leitao MM Jr ... -  《-》

Isolated tumor cells identified by sentinel lymph node mapping in endometrial cancer: Does adjuvant treatment matter?

To evaluate the outcome and the role of adjuvant treatment in the management of patients with endometrial cancer and isolated tumor cells (ITCs) identified by SLN mapping. This single center study identified all patients undergoing hysterectomy, salpingo-oophorectomy, lymphadenectomy and SLN mapping for endometrial cancer between November 2010 and December 2015. Data was prospectively collected. Progression-free survival was analyzed according to the Kaplan-Meier method and compared using the log-rank test. A total of 519 patients were included. Overall, 85 patients (16.4%) were found to have SLN metastases of which 43 (51%) were macrometastasis, 11 (13%) micrometastasis (MM) and 31 (36%) ITC. Eleven (35%) of patients with ITCs received adjuvant chemotherapy±whole pelvic radiation therapy (WPRT), 10 (32%) received WPRT, and 10 (32%) received either no adjuvant treatment or vault brachytherapy (VBT) only. ITC patients received significantly less chemotherapy (p=0.0001) and WPRT (p=0.007) compared to patients with macrometastasis. Of note, ITC were not considered node positive in our study. With a median follow-up of 29months (range: 0-67), the progression free survival (PFS) at 3-years for the ITC patients was 95.5%, similar to node negative (87.6%) and micrometastasis patients (85.5%), but statistically better than patients with macrometastasis (58.5%) (p=0.0012). Only 1/31 patient with ITC recurred (IB, 7cm carcinosarcoma) despite adjuvant treatments. None of the ITC patients with endometrioid histology recurred (0/28) and none of the ITC patients who did not receive adjuvant treatment or VBT recurred (0/10). Patients with endometrial cancer found to have SLN ITCs have an excellent outcome. The use of adjuvant treatment should be tailored to uterine factors and histology and not solely based on the presence of ITCs. Patients with ITCs and otherwise low-risk uterine disease probably derive little benefit from receiving additional treatments. More studies are needed to confirm our results.

Plante M ，Stanleigh J ，Renaud MC ，Sebastianelli A ，Grondin K ，Grégoire J ... -  《-》

Sentinel lymph nodes (SLN) in endometrial cancer: The relationship between primary tumor histology, SLN metastasis size, and non-sentinel node metastasis.

To examine sentinel lymph node pathology and describe relationships to uterine pathology, non-sentinel pelvic lymph nodes, and para-aortic lymph nodes. Patients with apparent uterine-confined endometrial cancer underwent robotic hysterectomy, SLN mapping, completion pelvic lymphadenectomy (LND), and para-aortic (PaLND) directed by frozen section. Patients were risk stratified by histology: low-risk (LR) endometrioid <50% depth-of-invasion (DOI), intermediate-risk (IR) endometrioid ≥50% DOI, and high-risk (HR) type II histology for comparison to other pelvic/aortic metastases. 414 patients were stratified: 275 LR, 80 IR, and 59 HR cases. PaLND was performed in 84.2% of IR/HR patients and 25.1% LR patients. Pelvic node metastasis was detected in 11.6% LR, 50.0% IR, and 39.0% HR patients. PaLN metastasis was detected in 2.9% LR, 11.3% IR, and 16.9% HR patients. Proportionally, isolated tumor cells (ITC) SLNs were more common in LR or IR vs. HR group (51.6% and 44.7% vs. 15.0%, p < 0.05). The SLN false negative rates (FNR) were 0% LR, 2.5% IR, and 5.1% HR. Non-sentinel pelvic node metastases were present in 28(31.5%) of all SLN+ cases, but only 3(8.3%) of SLN with ITC. PaLN metastasis was found in 18.8% LR, 11.8% IR, and 33.3% HR cases with ITC SLNs. After controlling for DOI, LVSI, and grade, ITC-positive SLNs had a significant association with non-sentinel pelvic and aortic metastasis (p = 0.03 and p = 0.008, respectively). Patients with HR histology have more micro/macro-metastases in both SLNs and non-SLN metastases compared to LR/IR patients. SLN ITCs were associated with a clinically significant incidence of PaLN metastasis across all histology risk groups. There were no cases of isolated aortic node metastasis in this study. SLN mapping had an increased, although clinically acceptable FNR in the HR cohort compared to LR patients.

Kennard JA ，Stephens AJ ，Ahmad S ，Zhu X ，Singh C ，McKenzie ND ，Kendrick JE ，Holloway RW ... -  《-》

Lymphovascular space invasion and positive pelvic lymph nodes are independent risk factors for para-aortic nodal metastasis in endometrioid endometrial cancer.

Para-aortic lymph node dissemination in endometrioid endometrial cancer is uncommon, and systematic para-aortic lymph node dissection increases morbidity. The purpose of this study was to identify a subgroup of endometrioid endometrial cancer patients who did not require para-aortic lymphadenectomy. All patients who had undergone surgery for endometrioid endometrial cancer between 1 January 1995 and 31 December 2012 were retrospectively reviewed. Patients with higher risk factors for nodal metastasis and inadequate lymphadenectomy were excluded. Para-aortic lymph node dissemination was defined as nodal metastasis when pelvic and para-aortic lymph node dissection was performed, when para-aortic lymph node recurrence occurred after negative para-aortic lymph node dissection or when para-aortic lymph node dissection was not performed. Multivariate logistic regression models were used to identify the pathological features as predictors for para-aortic lymphatic dissemination. A total of 827 patients were assessed, 516 (62.4%) of whom underwent pelvic and para-aortic lymph node dissection. Sixty-seven (13%) patients (37 with only pelvic, 26 with pelvic and para-aortic, and 4 with only para-aortic metastasis) had positive lymph nodes in the pelvic and para-aortic lymph node dissection group. Multivariate analysis confirmed positive pelvic nodes (odds ratio 20.58; p<0.001) and lymphovascular space invasion (odds ratio 8.10; p=0.022) as independent predictors of para-aortic lymphatic dissemination. When these two factors were absent (in 83% of patients), the predicted probability of para-aortic lymph node metastasis was 0.1%. Positive pelvic nodes and lymphovascular space invasion are highly associated with para-aortic lymph node metastasis. These markers may be useful for identifying those patients who require para-aortic lymph node dissection.

Solmaz U ，Mat E ，Dereli ML ，Turan V ，Tosun G ，Dogan A ，Sanci M ，Ozdemir IA ，Pala EE ... -  《-》