Pelvic Sentinel lymph node detection in High-Risk Endometrial Cancer (SHREC-trial)—the final step towards a paradigm shift in surgical staging

ObjectiveTo report on the performance of hysteroscopic injection of tracers (indocyanine green (ICG) and technetium-99m (Tc-99m)) for sentinel lymph node (SLN) mapping in endometrial cancer.MethodsSingle-center retrospective evaluation of consecutive patients who underwent SLN mapping following hysteroscopic peritumoral injection of tracer. Detection rate (overall/bilateral/aortic) diagnostic accuracy, and oncologic outcomes were evaluated.ResultsA total of 221 procedures met the inclusion criteria. Mean patient age was 60 (range 28–84) years and mean body mass index was 26.9 (range 15–47) kg/m2 . In 164 cases (70.9%) mapping was performed laparoscopically. The overall detection rate of the technique was 94.1% (208/221 patients). Bilateral pelvic mapping was found in 62.5% of cases with at least one SLN detected and was more frequent using ICG than with Tc-99m (73.8% vs 53.3%; p<0.001). In 47.6% of cases SLNs mapped in both pelvic and aortic nodes, and in five cases (2.4%) only in the aortic area. In eight patients (3.8%) SLNs were found in aberrant (parametrial/presacral) areas. Mean number of detected SLNs was 3.7 (range 1–8). In 51.9% of cases at least one node other than SLNs was removed. Twenty-six patients (12.5%) had nodal involvement: 12 (46.2%) macrometastases, six (23.1%) micrometastases, and eight (30.7%) isolated tumor cells. In 12 cases (46.8%) the aortic area was involved. Overall, 6/221 (2.7%) patients had isolated para-aortic nodes. Three false-negative results were found, all in the Tc-99m group. All had isolated aortic metastases. Overall sensitivity was 88.5% (95% CI 71.7 to 100.0) and overall negative predictive value was 96.5% (95% CI 86.8 to 100.0). There were 10 (4.8%) recurrences: five abdominal/distant, four vaginal, and one nodal (in the aortic area following a unilateral mapping plus side-specific pelvic lymphadenectomy). Most recurrences (9/10 cases) were patients in whom a completion lymphadenectomy was performed. No deaths were reported after a mean follow-up of 47.7 months.ConclusionsHysteroscopic injection of tracers for SLN mapping in endometrial cancer is as accurate as cervical injection with a higher detection rate in the aortic area. ICG improves the bilateral detection rate. Adding lymphadenectomy to SLN mapping does not reduce the risk of relapse.

Section: Discussioncontrasting

confidence: 46%

Section: Discussionmentioning

confidence: 99%

Sentinel lymph node mapping in endometrial cancer: performance of hysteroscopic injection of tracers

Martinelli

Ditto

Bogani

et al. 2020

“…On the other hand, in the SHREC study no complications associated with the SLN procedure were observed, indicating the importance of surgical experience. Another study performed at our institution showed a 13-fold decrease in symptomatic lower limb lymphedema (18.1% compared with 1.3%) and a 5-fold decrease in the incidence of pelvic lymphoceles (13.3% compared with 2.6%) after SLN only compared with a full pelvic lymph node dissection, demonstrating the potential of the SLN concept in decreasing postoperative lymphatic complications 2 11 13 14…”

Section: Introductionmentioning

confidence: 76%

“…Therefore, the principle of a full site-specific lymphadenectomy in case of non-mapping may be questioned from a morbidity perspective, particularly in low risk endometrial cancer patients. The additional 30 min required in the Pelvic SLN detection in the High-Risk Endometrial Cancer (SHREC) study for the SLN procedure, where dissection along both the upper and lower paracervical pathways were performed, is likely too time-consuming to motivate a similar SLN algorithm in presumed low-risk patients, taking into account that surgeries were performed by a few well experienced surgeons 2 11 13. On the other hand, in the SHREC study no complications associated with the SLN procedure were observed, indicating the importance of surgical experience.…”

Section: Introductionmentioning

confidence: 99%

Pelvic sentinel lymph node biopsy in endometrial cancer—a simplified algorithm based on histology and lymphatic anatomy

Bollino

Geppert

Lönnerfors

et al. 2020

Self Cite

ObjectiveTo achieve the full potential of sentinel lymph node (SLN) detection in endometrial cancer, both presumed low- and high-risk groups should be included. Perioperative resource use and complications should be minimized. Knowledge on distribution and common anatomical sites for metastatic SLNs may contribute to optimizing the concept while maintaining sensitivity. Proceeding from previous studies, simplified algorithms based on histology and lymphatic anatomy are proposed.MethodsData on mapping rates and locations of pelvic SLNs (metastatic and non-metastatic) from two previous prospective SLN studies in women with endometrial cancer were retrieved. Cervically injected indocyanine green was used as a tracer and an ipsilateral re-injection was performed in case of non-display of the upper and/or lower paracervical pathways. A systematic surgical algorithm was followed with clearly defined SLNs depicted on an anatomical chart. In high-risk endometrial cancer patients, removal of SLNs was followed by a pelvic and para-aortic lymphadenectomy.Results423 study records were analyzed. The bilateral mapping rates of the upper and lower paracervical pathways were 88.9% and 39.7%, respectively. 72% of all SLNs were typically positioned along the upper paracervical pathway (interiliac and/or proximal obturator fossa) and 71 of 75 (94.6%) of pelvic node positive women had at least one metastatic SLN at either of these positions. Women with grade 1–2 endometroid cancers (n=275) had no isolated metastases along the lower paracervical pathway compared with two women with high-risk histologies (n=148).ConclusionSLNs along the upper paracervical pathway should be identified in all endometrial cancer histological subtypes; removal of nodes at defined typical positions along the upper paracervical pathway may replace a site-specific lymphadenectomy in case of non-mapping despite tracer re-injection. Detection of SLNs along the lower paracervical pathway can be restricted to high-risk histologies and a full pre-sacral lymphadenectomy should be performed in case of non-display.

“…Our study confirmed that the incidence of nodal metastases increased from 13% in the group of patients submitted to standard lymphadenectomy to 25% in the group of patients who underwent SLN biopsy. Furthermore, even if prospective data are needed to verify the reliability and the applicability of this SLN strategy in routine practice over standard lymphadenectomy in high-risk subgroups of women,15–17 there is also new evidence of promising results in this subgroup of patients with apparently confined endometrial cancer.…”

Section: Discussionmentioning

confidence: 99%

Combining positron emission tomography/computed tomography, radiomics, and sentinel lymph node mapping for nodal staging of endometrial cancer patients

Crivellaro

Landoni

Elisei

et al. 2020

ObjectiveTo evaluate the combination of positron emission tomography/computed tomography (PET/CT) and sentinel lymph node (SLN) biopsy in women with apparent early-stage endometrial carcinoma. The correlation between radiomics features extracted from PET images of the primary tumor and the presence of nodal metastases was also analyzed.MethodsFrom November 2006 to March 2019, 167 patients with endometrial cancer were included. All women underwent PET/CT and surgical staging: 60/167 underwent systematic lymphadenectomy (Group 1) while, more recently, 107/167 underwent SLN biopsy (Group 2) with technetium-99m +blue dye or indocyanine green. Histology was used as standard reference. PET endometrial lesions were segmented (n=98); 167 radiomics features were computed inside tumor contours using standard Image Biomarker Standardization Initiative (IBSI) methods. Radiomics features associated with lymph node metastases were identified (Mann-Whitney test) in the training group (A); receiver operating characteristic (ROC) curves, area under the curve (AUC) values were computed and optimal cut-off (Youden index) were assessed in the test group (B).ResultsIn Group 1, eight patients had nodal metastases (13%): seven correctly ridentified by PET/CT true-positive with one false-negative case. In Group 2, 27 patients (25%) had nodal metastases: 13 true-positive and 14 false-negative. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT for pelvic nodal metastases were 87%, 94%, 93%, 70%, and 98% in Group 1 and 48%, 97%, 85%, 87%, and 85% in Group 2, respectively. On radiomics analysis a significant association was found between the presence of lymph node metastases and 64 features. Volume-density, a measurement of shape irregularity, was the most predictive feature (p=0001, AUC=0,77, cut-off 0.35). When testing cut-off in Group B to discriminate metastatic tumors, PET false-negative findings were reduced from 14 to 8 (-43%).ConclusionsPET/CT demonstrated high specificity in detecting nodal metastases. SLN and histologic ultrastaging increased false-negative PET/CT findings, reducing the sensitivity of the technique. PET radiomics features of the primary tumor seem promising for predicting the presence of nodal metastases not detected by visual analysis.