Introduction The low accuracy of pre-operative imaging techniques for prediction of nodal status strengthens the relevance of sentinel lymph node (SLN) biopsy in endometrial cancer, although the optimal method for its detection is still under investigation. The increasing use of indocyanine green (ICG) has aroused concern about its enhanced visualization of lymphatic channels, which could lead to a specimen that is thought to be nodal tissue not subsequently yielding a lymph node on pathologic analysis ('empty node packet'). Our main objective was to compare the overall and bilateral detection rates for SLN biopsy using two combined techniques: technetium-99m-ICG (Tc-99m-ICG) versus technetium-99m-methylene blue (Tc-99m-MB). Our secondary aim was to compare the ‘empty node packet’ rates between the two cohorts. Methods A prospective, non-randomized, single-center trial including patients diagnosed with endometrial cancer (any grade or histology) in pre-operative early stage, and operated on between February 2017 and July 2019. All tracers were injected intracervically. Pelvic and aortic lymphadenectomy were performed on patients at intermediate or high risk of recurrence pre-operatively. All SLNs were sent for intra-operative frozen section and afterwards processed following an ultrastaging protocol. Results Eighty-four patients were included, 58% (n=49) in the Tc-99m-MB group and 42% (n=35) in the Tc-99m-ICG group. Overall detection rate was 93% and was not statistically different between the two groups. A better bilateral detection rate was observed among Tc-99m-ICG patients (69% vs 41%, p=0.012). The 'empty node packet' rate was 4% in the Tc-99m-ICG cohort and 0% in the Tc-99m-MB cohort (p=0.032). Discussion Tc-99m-ICG is a feasible, safe technique for SLN biopsy in early-stage endometrial cancer, and appears to be superior in terms of bilateral detection to Tc-99m-MB. The addition of Tc-99m to ICG could decrease the rate of 'empty node packets' and better define the anatomic location of SLNs in patients with endometrial cancer.

Objectives To investigate the pattern of first recurrence of disease in patients with endometrial cancer according to molecular classification, and to assess the independent role of molecular profiling in each type of failure. Methods Retrospective single-center study including patients diagnosed with endometrial cancer stage I–IVB (International Federation of Gynecology and Obstetrics 2009) between December 1994 and May 2022, who underwent primary surgical treatment and had a complete molecular profile. First recurrence was classified as isolated or multiple, and as vaginal, pelvic, peritoneal, nodal, and distant according to its location. The log-rank test and univariate and multivariate adjusted Cox regression models were used for comparison between groups. Results A total of 658 patients were included. Recurrence was observed in 122 patients (18.5%) with a recurrence rate of 12.4% among mismatch-repair deficient tumors, 14.5% among non-specific molecular profile, 2.1% among POLE-mutated, and 53.7% among p53-abnormal tumors. Recurrences were found to be isolated in 80 (65.6%) and multiple in 42 (34.4%) patients, with no differences in molecular subtype (p=0.92). Patients with p53-abnormal tumors had a recurrence mainly as distant (28.4%) and peritoneal (21.1%) disease, while patients with non-specific molecular profile tumors presented predominantly with distant failures (10.3%), and mismatch-repair deficient tumors with locoregional recurrences (9.4%). On multivariate analysis, p53-abnormal molecular profile was the only independent risk factor for peritoneal failure (OR=8.54, 95% CI 2.0 to 36.3). Vaginal recurrence was independently associated with p53-abnormal molecular profile (OR=6.51, 95% CI 1.1 to 37.4) and lymphovascular space invasion. p53-abnormal and non-specific molecular profiles were independent predictors for distant recurrence (OR=3.13, 95% CI 1.1 to 8.7 and OR=2.35, 95% CI 1.1 to 5.0, respectively), along with lymphovascular space invasion and high-grade tumors. Molecular profile was not independently associated with pelvic and nodal recurrences. Conclusions Endometrial cancer featured different patterns of recurrence depending on the molecular profile. p53-abnormal molecular profiling was the only independent risk factor for peritoneal relapse, while non-specific molecular profile showed a strong association with distant failures.