Comparison of Two-Position and Four-Position Cervical Injection Techniques for Sentinel Lymph Node Mapping in Endometrial Cancer Using Methylene Blue

Endometrial Neoplasms

Endometrial Neoplasms — a type of gynecological cancer.

Comparison of tracer application methods for sentinel lymph node detection in open surgery patients with endometrial cancer: a retrospective cohort study

This study aimed to evaluate the effectiveness of different tracers´ application techniques for sentinel lymph node (SLN) detection in women with endometrial cancer undergoing laparotomy. Additionally, potential risk factors for SLN detection failure were assessed. We retrospectively analyzed data from 248 endometrial cancer patients who underwent abdominal surgery with SLN mapping between January 2020 and March 2024. Statistical analyses were conducted using the Wilcoxon rank sum test for continuous variables and either Pearson's chi-square test or Fisher's exact test for categorical variables, with a significance level set at p < 0.05. Group I + S consisted of 147 women with intracervical and subserosal tracers´application and group I + I included 101 women with intracervical and intrafundal application. Successful detection of SLN on both sides was achieved in 39.9% (99/248) of all patients, in 38.1% (56/147) in the I + S group and in 42.6% (43/101) in the I + I group, respectively. SLNs were identified in 32.7% (81/248) of all patients on only one side of the pelvis, in 31.3% (46/147) in the I + S and in 34.7% (35/101) in the I + I group, respectively. No SLNs were detected in 27.4% (68/248) of all subjects, comprising 30.6% (45/147) from the I + S and 22.8% (23/101) from the I + I group. Although the success rate of SLN detection was higher in the I + I group and on the right side of the pelvis regardless of the detection method, these differences were not statistically significant. An age exceeding 66.3 years was recognized as a critical risk factor for successful detection, other followed factors did not demonstrate a statistically significant impact on overall detection success. Additional significant risk factors were identified: depth of tumor myometrial invasion on the right side, history of pelvic surgery, and total tumor volume on the left side. The study did not reveal significant differences in SLN mapping success between the groups receiving intracervical + intrafundal and intracervical + subserosal tracers´applications among endometrial cancer patients treated via open surgery. Overall, older age emerged as the most critical risk factor for SLN detection failure, while other assessed factors did not show a statistically significant impact on overall detection success. Institution University Hospital Královské Vinohrady, Prague, Czech Republic. EK-VP-21-0-2023. Date of registration 7-JUN-2023. This study was retrospectively registered in compliance with the Declaration of Helsinki.

Sentinel lymph node mapping in endometrial cancer: A comparison of main national and international guidelines

AbstractObjectivesTo compare national and international guidelines regarding sentinel lymph node (SLN) mapping in endometrial cancer.MethodsA descriptive comparative study of the National Comprehensive Cancer Network (NCCN), the Society of Gynecologic Oncology (SGO), the European Society of Gynecological Oncology (ESGO), the British Gynecological Cancer Society (BGCS), and the Japan Society of Gynecologic Oncology (JSGO) guidelines.ResultsThere is a broad consensus that SLN mapping is an appropriate alternative to pelvic lymphadenectomy for uterine‐confined endometrioid endometrial cancer (five of five guidelines). It is broadly accepted that a full lymphadenectomy should be performed in case of failed SLN mapping (four of five guidelines), and that mapping with the fluorescent dye indocyanine green is superior to other methods (four of five guidelines). It is agreed that the cervix is the preferable site for dye injection (four of five guidelines), and pathology ultrastaging is advocated by most guidelines (three of five guidelines). Regarding high‐risk patients (i.e., high‐grade histology and non‐endometroid carcinomas), some guidelines accept (three of five), but others currently do not advocate (one of five guidelines), SLN mapping as a sole method for lymph node evaluation. There is no consensus regarding para‐aortic lymph node evaluation in pelvic SLN‐positive patients.ConclusionGuidelines for SLN mapping are comparable with regards to surgical technique, ultrastaging, and management in case of failed mapping. Nevertheless, some variations exist regarding the management of high‐grade histology and positive pelvic lymph nodes.

Sentinel lymph node mapping versus sentinel lymph node mapping with systematic lymphadenectomy in endometrial cancer: an open-label, non-inferiority, randomized trial (ALICE trial)

Growing evidence suggest that sentinel lymph node (SLN) biopsy in endometrial cancer accurately detects lymph node metastasis. However, prospective randomized trials addressing the oncological outcomes of SLN biopsy in endometrial cancer without lymphadenectomy are lacking. The present study aims to confirm that SLN biopsy without systematic node dissection does not negatively impact oncological outcomes. We hypothesized that there is no survival benefit in adding systematic lymphadenectomy to sentinel node mapping for endometrial cancer staging. Additionally, we aim to evaluate morbidity and impact in quality of life (QoL) after forgoing systematic lymphadenectomy. This is a collaborative, multicenter, open-label, non-inferiority, randomized trial. After total hysterectomy, bilateral salpingo-oophorectomy and SLN biopsy, patients will be randomized (1:1) into: (a) no further lymph node dissection or (b) systematic pelvic and para-aortic lymphadenectomy. Inclusion criteria are patients with high-grade histologies (endometrioid G3, serous, clear cell, and carcinosarcoma), endometrioid G1 or G2 with imaging concerning for myometrial invasion of ≥50% or cervical invasion, clinically suitable to undergo systematic lymphadenectomy. The primary objective is to compare 3-year disease-free survival and the secondary objectives are 5-year overall survival, morbidity, incidence of lower limb lymphedema, and QoL after SLN mapping ± systematic lymphadenectomy in high-intermediate and high-risk endometrial cancer. 178 participants will be randomized in this study with an estimated date for completing accrual of December 2024 and presenting results in 2027. NCT03366051.

Uptake and outcomes of sentinel lymph node mapping in women undergoing minimally invasive surgery for endometrial cancer

AbstractObjectiveTo examine the patterns and outcomes of sentinel lymph node (SLN) assessment in women with endometrial cancer.DesignRetrospective cohort study.SettingUnited States inpatient and outpatient hospital services.PopulationWomen with endometrial cancer who underwent a laparoscopic or robotic‐assisted hysterectomy.MethodsThe Perspective Database from 2012 to 2018 was used. Performance of lymph node dissection was classified as SLN mapping, lymph node dissection or no nodal evaluation. Adjusted regression models were developed to examine the association between SLN mapping and morbidity and cost.Main Outcome MeasuresUtilisation rates, morbidity and cost of both lymph node dissection and SLN mapping.ResultsAmong 45 381 patients, SLN mapping was performed for 7768 patients (17.1%), lymph node dissection was performed for 23 214 patients (51.2%) and no lymphatic evaluation was performed for 14 399 patients (31.7%). SLN mapping increased from 1.8% in 2012 to 35.3% in 2018, whereas the rate of lymph node dissection decreased from 63.5% to 39.1% (p &lt; 0.001). Among women who underwent nodal evaluation, residence in the west, White race and use of robotic‐assisted hysterectomy were associated with SLN mapping (p &lt; 0.05 for all). The complication rate was 5.9% for SLN mapping, compared with 7.3% in those that underwent lymph node dissection (aRR 0.85, 95% CI 0.77–0.95). The median hospital costs for women who underwent SLN mapping ($10 479) and lymph node dissection ($10 747) were higher than for those who did not undergo nodal assessment ($9149) (p &lt; 0.001).ConclusionsThe performance of SLN mapping is increasing for endometrial cancer. Compared with lymph node dissection, SLN mapping is associated with lower morbidity. SLN mapping significantly increases the costs compared with hysterectomy alone.Tweetable AbstractSLN mapping is increasing rapidly for endometrial cancer and is associated with decreased perioperative morbidity.

Diagnostic accuracy of sentinel node biopsy in non-endometrioid, high-grade and/or deep myoinvasive endometrial cancer: A Turkish gynecologic oncology group study (TRSGO-SLN-006)

This study aimed to evaluate the diagnostic accuracy of the sentinel lymph node (SLN) mapping algorithm in high-risk endometrial cancer patients. Two hundred forty-four patients with non-endometrioid histology, grade 3 endometrioid tumors and/or tumors with deep myometrial invasion were enrolled in this retrospective, multicentric study. After removal of SLNs, all patients underwent pelvic ± paraaortic lymphadenectomy. Operations were performed via laparotomy, laparoscopy or robotic surgery. Indocyanine green (ICG) and methylene blue (MB) were used as tracers. SLN detection rate, sensitivity, negative predictive value (NPV) and false-negative rate (FNR) were calculated. Surgeries were performed via laparotomy in 132 (54.1%) patients and 152 (62.3%) underwent both bilateral pelvic and paraaortic lymphadenectomy. At least 1 SLN was detected in 222 (91%) patients. Fifty-five (22.5%) patients had lymphatic metastasis and 45 patients had at least 1 metastatic SLN. Lymphatic metastases were detected by side-specific lymphadenectomy in 8 patients and 2 patients had isolated paraaortic metastasis. Overall sensitivity, NPV and FNR of SLN biopsy were 81.8%, 95% and 18.2%, respectively. By applying SLN algorithm steps, sensitivity and NPV improved to 96.4% and 98.9%, respectively. For grade 3 tumors, sensitivity, NPV and FNR of the SLN algorithm were 97.1%, 98.9% and 2.9%. SLN algorithm had high diagnostic accuracy in high-risk endometrial cancer. All pelvic metastases were detected by the SLN algorithm and the isolated paraaortic metastasis rate was ignorable. But long-term survival studies are necessary before this approach becomes standard of care.

Laparoscopic sentinel node mapping with intracervical indocyanine green injection for endometrial cancer: the SENTIFAIL study – a multicentric analysis of predictors of failed mapping

Laparoscopy is commonly used for endometrial cancer treatment, and sentinel lymph node (SLN) mapping has become the standard procedure for nodal assessment. Despite the standardization of the technique, there is no definitive data regarding its failure rate. The objective of this study is to identify factors associated with unsuccessful SLN mapping in endometrial cancer patients undergoing laparoscopic SLN mapping after intracervical indocyanine green (ICG) injection. We retrospectively evaluated a consecutive series of endometrial cancer patients who underwent laparoscopic SLN mapping with intracervical ICG injection, in four oncological referral centers from January 2016 to July 2019. Inclusion criteria were biopsy-proven endometrial cancer, total laparoscopic approach, and intracervical ICG injection. Exclusion criteria were evidence of lymph node involvement or extrauterine disease at pre-operative imaging, synchronous invasive cancer, the use of tracers different from ICG, and the use of neoadjuvant treatment. Bilateral and failed bilateral SLN mapping groups were compared for clinical and pathological features. In patients with an unsuccessful procedure, side-specific lymphadenectomy was performed. Logistic regression was used to identify predictors of failure. A total of 376 patients were included in the study. The overall bilateral and unilateral SLN detection rates were 96.3%, 76.3%, and 20.0% respectively. The failed bilateral mapping detection rate was 23.7%. The median number of sentinel nodes removed was 2.2 (range, 0-5). After multivariate analysis, lymph vascular space involvement [OR 2.4 (1.04-1.12), P=0.003], non-endometrioid histology [OR 3.0 (1.43-6.29), P=0.004], and intraoperative finding of enlarged lymph node [OR 2.3 (1.01-5.31), P=0.045] were identified as independent predictors of failure of SLN mapping. Lymph vascular space involvement, non-endometrioid histology, and intra-operative finding of enlarged lymph nodes were identified as independent risk factors for unsuccessful mapping in patients undergoing laparoscopic SLN mapping.

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

To 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. Patients 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. Of 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. This 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.

Aharon Dick

Andre Lopes

Giulio Sozzi

Glauco Baiocchi

Jason D Wright

Levon Badiglian-Filho

Reitan Ribeiro

Ricardo dos Reis

PhD, Professor, MD Hospital de Câncer de Barretos. Gynecologic Oncology Department

Stefano Restaino

Vito Andrea Capozzi