• Endometrial Neoplasms
• Sentinel Lymph Node
• SLN and Lympadenectomy

We read with interest the article from Capozzi et al,1 retrospectively comparing sentinel node mapping and full lymphadenectomy in 237 women with high-risk endometrial cancer between 2007 and 2019, with a median follow-up of 2.5 years. The authors argue that patients undergoing sentinel lymph node biopsy alone appear to have equivalent survival when compared with those who underwent full lymphadenectomy.

Furthermore, the post-hoc analysis performed on the subgroup of women with nodal metastasis showed no differences in either overall survival or disease-free survival among the groups. However, this highlights the main drawback of the study, which is mainly related to the non-comparability of the two groups (stage III 44.3% vs 57.2% of sentinel node alone vs lymphadenectomy; p=0.039), and the lack of a statistical difference in survival (disease-free survival: 83.7% vs 76.4%; overall survival: 96.1% vs 91.4%) is likely to be affected by the limited number of patients included in the analysis. This study, similar to other published retrospective series involving high-risk subgroups, is statistically underpowered to find a significant difference in survival.

We would like to discuss briefly two main aspects. Stage IIIC disease in the sentinel node group and in the lymphadenectomy group are inherently different, and it is like comparing apples with oranges. In fact, low volume metastasis may be missed by conventional pathological analysis, while ultrastaging allows tripling the identification of low volume metastases in the sentinel lymph nodes, therefore can be considered as ‘stage IIIC by accident’.2 Vice versa, women in the lymphadenectomy group usually have macrometastasis and are often subjected to a systematic lymphadenectomy in the presence of pre-operative suspicious findings or when discovered intra-operatively.

Interestingly, as proposed by some authors, a full lymphadenectomy seems to result in a favorable survival in women with apparently negative or with macroscopically positive nodes,3 suggesting a more aggressive behavior of the disease and therefore a greater risk of recurrence. In this subgroup of stage III disease it seems that chemotherapy plus radiation did not provide a survival benefit over chemotherapy alone.4

Thus, in the subgroup of women with pre-operative high-risk features, work-up appears critical in the triage of women candidates for sentinel node biopsy, or conversely those who may benefit from a full lymphadenectomy. The article by Capozzi et al did not report the type of imaging work-up, but this would be reasonably important in retrospective analysis to reduce the risk of patient selection bias. In this context, as proposed by Signorelli et al,5 in the subgroup of patients with high-risk endometrial cancer, performing a positron emission tomography (PET) scan can better identify those patients at risk of nodal involvement, thus allowing a more adequate surgical approach. More recently, use of PET radiomics to determine volume density features of primary tumors seems promising in predicting the presence of nodal metastases.6

In the subset of high-risk patients with endometrial cancer, optimal bilateral mapping can perform slightly worse; this can be reasonable in patients with a higher risk of nodal involvement that can also impact on the false negative rate of the sentinel node algorithm.7

Another critical point of the study by Capozzi et al arises from the evidence that more than 91% of women received adjuvant treatment. This result is not surprising in a high-risk setting, considering the new molecular characterization of each individual patient’s tumor. In this scenario, we would emphasize that understanding the impact of the type of nodal metastasis in the sentinel lymph node removed will be of primary importance; likewise the classification of the four subtypes set by The Cancer Genome Atlas,8 since integration of all the information will be useful for a more appropriate choice of adjuvant treatment.

Only large, well-designed, prospective trials will perhaps help us address the still unresolved issues in endometrial cancer for both low-risk and high-risk women.