Technetium-99m-indocyanine green versus technetium-99m-methylene blue for sentinel lymph node biopsy in early-stage endometrial cancer

Abstract

IntroductionThe 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.MethodsA 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.ResultsEighty-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).DiscussionTc-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.

Anatomic Asymmetry in Sentinel Lymph Node Detection in Endometrial Cancer

“…Kessous et al (15) reported higher unilateral and bilateral SLN detection rates of 97.5% and 81.3%, respectively, with concomitant use of ICG and Tc99m-FSC. Recently, Cabrera et al (16) demonstrated significantly higher bilateral detection rate among patients injected with Tc-99m and ICG patients (69%). Our data agrees, highlighting the superiority of Tc99m-ICG combination over Tc99m-FSC alone for bilateral detection (87.3% vs. 63.4%, p=0.0006).…”

Status of Sentinel Lymph Node Biopsy in Endometrial Cancer

“…A combination of ICG with Tc99m nanocolloid to show and detect sentinel lymph nodes in patients with endometrial cancer has recently come into the focus of scientific interest. Kessous et al reported in their study of 157 patients with endometrial cancer that a triple tracer combination (ICG, Tc99m and patent blue) does not lead to a significant improvement in the overall detection rate (93.5 vs. 97.5 %) and bilateral detection rate (80.5 vs. 81.3 %) compared with a double tracer combination (ICG and ▶ Table 2 Sentinel lymph node detection rates: overall and bilateral detection rates (modified and supplemented from [11] [43]. As regards the overall detection rate (93 vs. 94 %) there was no significant difference between the 2 groups, but the bilateral detection rate was significantly higher (69 vs. 41 %) in the patients who had mapping by means of a combination of ICG and Tc99m [43].…”

“…Kessous et al reported in their study of 157 patients with endometrial cancer that a triple tracer combination (ICG, Tc99m and patent blue) does not lead to a significant improvement in the overall detection rate (93.5 vs. 97.5%) and bilateral detection rate (80.5 vs. 81.3%) compared with a double tracer combination (ICG and Tc99m) 42 . In a group of 84 patients with endometrial cancer Cabrera et al compared the sentinel lymph node detection rate after mapping by a combination of ICG and Tc99m (35 patients) to mapping with the combination of ICG and methylene blue (49 patients) 43 . As regards the overall detection rate (93 vs. 94%) there was no significant difference between the 2 groups, but the bilateral detection rate was significantly higher (69 vs. 41%) in the patients who had mapping by means of a combination of ICG and Tc99m 43 .…”

“…In a group of 84 patients with endometrial cancer Cabrera et al compared the sentinel lymph node detection rate after mapping by a combination of ICG and Tc99m (35 patients) to mapping with the combination of ICG and methylene blue (49 patients) 43 . As regards the overall detection rate (93 vs. 94%) there was no significant difference between the 2 groups, but the bilateral detection rate was significantly higher (69 vs. 41%) in the patients who had mapping by means of a combination of ICG and Tc99m 43 .…”

“…An advantage of the combination of several tracers is the reduction in the rate of failed identification of the sentinel lymph node in endometrial cancer and avoidance of the so-called empty node packet phenomenon, which is described in association with injection of ICG only 43 . The FILM study reported empty node packets in 5% of samples and Thomaier et al described empty node packets in 7% of samples after imaging the lymph nodes with ICG 41 , 44 .…”