Nodal staging in high and high-intermediate risk endometrial cancer surgery: Which role in the molecular classification era?

Endometrial cancer is the most common gynecological malignancy in developed countries, whose prevalence continues to increase alongside the increasing prevalence of its risk factors, including obesity and metabolic syndrome, and as the result of a growing aging population [1]. Current guidelines mandate exploration of lymph nodes as part of surgical staging through a systematic lymphadenectomy or a sentinel node biopsy (SLNB) [2,3]. However, the impact on survival of retroperitoneal staging in presumed early-stage endometrial carcinoma is still debated: while retrospective studies have indicated the potential therapeutic impact of lymphadenectomy [4,5] and solid data highlighted the prognostic value of nodal dissection, its therapeutic potential was refuted by the findings of two randomized trial [6,7].

According to ESGO/ESTRO/ESP guidelines [3] SLNB can be considered for staging in patients with low and intermediate disease risk. In these groups, SLNB detects up to 6% metastatic nodal involvement, leading to an upgrade in risk classification and a change in adjuvant treatment. Regarding patients with high–intermediate risk (HIR)/high-risk (HR) disease, to date systematic pelvic and para-aortic lymphadenectomy is still suggested by international guidelines. However, SLNB has proved to be a safe alternative also in these subgroups of patients [8], [9], [10].

The indication to adjuvant therapy is tailored according to risk classification, derived from a combination of FIGO stage, conventional histological risk factors and molecular patterns [11,12]. In HIR patients, adjuvant external beam radiotherapy (EBRT) and/or brachytherapy (BT) is recommended, and additional adjuvant chemotherapy (CT) can be considered for high grade disease and substantial lymphovascular space invasion (LVSI). In HR subgroup, EBRT combined with chemotherapy or chemotherapy alone is the indicated treatment.

Nodal assessment contributes to define HR disease and the choice of adjuvant treatment for HIR cases. However, with the growing significance of molecular classification in delineating prognostic groups and guiding adjuvant therapies, the role of nodal assessment evolved and requires redefinition.

Primary outcome of the study was to determine the proportion of patients classified in HR group only on the basis of nodal staging, without any other features corresponding to this class. Secondary outcome was to evaluate the impact of nodal assessment on the decision for adjuvant treatment in both HR and HIR endometrial cancer patients submitted to surgery.

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