**5. Recommendations for the clinical application of selective sentinel node biopsy**

The published results of SLNB in EC have shown good diagnostic performance. SNLB is a promising and safe technique from the oncological point of view [10]. Given the mixed results, which have failed to show a therapeutic benefit [9], and the lack of long-term results [5], an appropriate interpretation is recommended [4, 29], considering SNLB a technique under study [79].

As with lymphadenectomy and adjuvant therapy, SNLB can be safely omitted for low-risk patients (endometrioid histology: IA G1, IA G2) [9, 56]. For intermediaterisk (endometrioid histology: IA G3, IB G1, IB G2) patients, SNLB has not shown a clear benefit in survival when performing systematic lymphadenectomy. This group does, however, have a greater risk of lymphatic involvement and typically undergo adjuvant therapy. SLNB in both patient groups has been shown to detect 2–3 times more cases of metastatic EC than lymphadenectomy, without changing the disease prognosis [87, 110]. These results justify extending the technique to low to intermediate risk, with the recommendation of including it in an algorithm or surgical protocol that includes the implementation when faced with failure of the technique. The potential benefit of detecting metastatic SLN in low-risk patients is however diluted by the low incidence of cases and the high proportion of low tumour volume. It appears we need to clarify the role of SLNB and the effect of low tumour volume, which is more frequently detected in this group [87, 110].

Two randomised clinical trials did not show that lymphadenectomy changed overall survival or relapse rates in high-risk patients [111–113], although retrospective series did show this change [114, 115]. The implementation of pelvic and paraaortic lymphadenectomy has been systematised due to the higher rate of lymphatic metastases and poorer prognosis associated with their detection. In contrast, sceptics of lymphadenectomy state that routine nodal assessment of high-risk patients rarely changes the recommendations for adjuvant therapy. EC (especially in high-risk cases) is not just a disease confined to the pelvis [51]. Patients with high-risk EC have a higher probability of recurrence and recidivism with or without detection of lymphatic metastases and should undergo systemic therapy regardless of the nodal state [116]. Nevertheless, published results on high-risk patients have shown no differences compared with those expected from studies that also include low- to intermediate-risk cases, with the same incidence of paraaortic metastasis estimated by lymphadenectomy. Survival data have shown no differences [30], which would assume that the benefit of SNLB in high-risk patients would be equivalent to lymphadenectomy alone [107, 108].

In terms of applying SLNB to high-risk patients, the greatest debate concerns paraaortic drainage, with a greater proportion of undetected metastatic paraaortic nonsentinel lymph nodes. A study by Naoura et al. [117] analysed 180 patients and achieved a much higher FNR in the high-risk group (2.3 vs. 20%; p < 0.001). In this study, it was much more likely that the high-risk subtype (7 vs. 28%; p = 0.03) and the nonendometrioid type (8 vs. 29%; p = 0.02) were poorly assessed.

The FIRES study [75] on 385 patients represents the largest prospective series to date and included low and high-risk patients, achieving a sensitivity of 97.2% and

an NPV of 99.6%. Fifty percent of detected metastatic SLNs were in patients with low-risk EC, the most incidental group. Only 1% were isolated paraaortic metastases, with an FNR of 2.7%. Barlin et al. [3] and the FIRES study concluded that a pelvically located SLN could be sufficient for directing the treatment [75].

In the study by Papadia et al. [119], the implementation of at least 20

FNR, improving the accuracy of the technique.

[30], which concluded with the following recommendations:

detection has a potential effect on staging.

*Role of Sentinel Node Biopsy in Endometrial Cancer DOI: http://dx.doi.org/10.5772/intechopen.89949*

procedures decreased the number of SLNs obtained without compromising the

• The histological analysis should be performed by ultrastaging. Although the implication and proper management of low tumour volume are not known, its

• Lymphatic mapping implementation is contraindicated in uterine sarcoma.

Recently, the SGO published a first consensus on the application of SLNB in EC

• Lymphatic mapping with cervical injection accurately predicts the detection of lymphatic metastasis, with an FNR <5%. In institutions with higher FNRs, the

previously indicated) until an FNR <5% has been ensured. Similarly, the SGO suggests adopting the indications of the American Society of Clinical Oncology applied to SLNB in breast cancer, such that lymphadenectomy is completed after SLNB in the first 20–30 cases. For low-risk patients, the recommendation is to increase the number of supervised cases during the learning process, given

• The injection of radiocolloid and dye is acceptable. If ICG is available, it should

confinement to the uterus, lymphadenectomy can be skipped, performing only

implementation of lymphadenectomy should be maintained (if it was

the lower risk of detecting lymphatic metastases [36, 120].

• For patients with low- to intermediate-grade type I EC and tumour

• Although SLNB has been shown to increase the detection of lymphatic metastases, patients should be informed of the potential risk of undetected

• Ultrastaging is recommended in the analysis of the SLN, although its

[30]. The combination of pelvic and paraaortic lymphadenectomy is reasonable until more safety and efficacy data for SLNB are available.

involvement in detecting ITC requires more research.

• The main demonstrated usefulness of SLNB is in detecting pelvic metastasis. The decision to perform paraaortic lymphadenectomy is at the surgical team's discretion, considering the patient's clinicopathological characteristics.

• The application of SLNB to high-risk patients (type 1 G3 and type 2 histology) following the NCCN algorithm is feasible and has had good published results

be used instead.

the SLNB.

occult disease.

**Abbreviations**

**193**

CT chemotherapy CK19 cytokeratin 19

EC endometrial cancer

EBRT external boost radiotherapy

In light of these results and lacking a therapeutic benefit for lymphadenectomy, the current guidelines recommend that only pelvic SLNs should be determined (and with caution) in this high-risk patient group [5, 30]. Until there is better evidence, the recommendation is to perform systematic lymphadenectomy adding SLNB, which a number of authors have labelled as 'high-precision lymphadenectomy'.

To decrease the number of faults in the technique and the risk of underdiagnosis in high-risk cases, several research groups have performed PET-CT, excluding cases with peritoneal or lymphatic uptake [118]. Other authors have included postoperative scans or PET in cases in which the paraaortic lymphadenectomy was not completed [30]. Another option for managing high-risk patients includes implementing a combined injection pathway, ensuring both pelvic and paraaortic drainage.

The Selective Targeting of Adjuvant Therapy in Endometrial Cancer (STATEC) in the United Kingdom [30] and the Evaluation of Sentinel Node Policy in Early Stage Endometrial Carcinomas at Intermediate and High Risk of Recurrence (SENTIRAD) in France are two studies currently underway on high-risk patients, comparing the effect of SLNB versus systematic lymphadenectomy (bilateral pelvic and paraaortic) in high-risk EC in initial clinical stages. The STATEC study compares SLNB versus lymphadenectomy with the patient as the same control. The SENTIRAD study randomised patients to SLNB or lymphadenectomy, following an algorithm that performs bilateral pelvic and paraaortic lymphadenectomy when faced with a failure in detection or unilateral detection.

In 2014, the NCCN clinical guidelines assessed the technique as an acceptable alternative to systematic lymphadenectomy in selected cases [36]. In the latest edition, NCCN [5] (v.3.2019) accepted the technique as category 2A (based on lower level evidence with uniform consensus by the expert panel that the procedure was appropriate) and established a number of recommendations:


In the study by Papadia et al. [119], the implementation of at least 20 procedures decreased the number of SLNs obtained without compromising the FNR, improving the accuracy of the technique.


Recently, the SGO published a first consensus on the application of SLNB in EC [30], which concluded with the following recommendations:

