Introduction/Background The primary endpoint of the present study was to assess the role of systemic inflammatory and molecular markers on DFS in patients with apparent early-stage endometrial cancer.

Methodology Retrospective, single-center, observational study. Patients with apparent endometrial cancer undergoing primary surgery between 06/2013–06/2019 were included. Data on systemic inflammatory markers were calculated on complete blood count performed at time of anesthetic assessment (1–30-days before surgery). Information about molecular markers P53, MLH1, MSH2, MSH6, PMS2, ER, PR and MMR stability was retrieved by immunohistochemistry (IHC) analysis of tumor tissue on uterus histology. Analyzed inflammatory markers included neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), eosinophil-lymphocyte ratio (ELR), monocyte-lymphocyte ratio (MLR), systemic immune inflammation index (SII), (eosinophil x neutrophil)/lymphocyte (ENL) and fibrinogen-albumin ratio (FAR). The ROC curve was used to determine the optimal cut-off value of different baseline inflammatory biomarkers for the DFS analysis.

Results Characteristics of 495 included patients are showed in table 1. Univariate analysis showed that following inflammatory markers values were significantly associated with worse DFS: NLR≥3.5 (HR:2.424;95%CI:1.512–3.886;p<0.001), SII≥1050 (HR:2.738;95%CI:1.665–4.502;p<0.001), PLR≥250 (HR:2.747;95%CI:1.453–5.194;p=0.002), FAR≥10 (HR: 1.841;95%CI:1.138–2.978;p=0.013), MLR≥0.3 (HR:2.288; 95%CI:1.409–3.716;p<0.001). When stratifying according to molecular risk-groups from ESGO-ESTRO-ESP-2021 guidelines, we found that in MMRd patients, patients with SII<1050 had better 3-year DFS than patients with SII≥1050 (91.0% versus 60.0%;p=0.002). Similarly, we found that in MMRd patients and p53 mutated patients, patients with PLR<250 had better 3-year DFS than those with PLR≥250 (90.1% versus 62.5%,p=0.020 and 74.9% versus 33.3%,p=0.045, respectively).Multivariable analysis including molecular and systemic inflammatory markers showed that PLR≥250 was independently associated with increased risk of recurrence.

Conclusion SII and PLR were the systemic inflammatory markers with major impact on recurrence risk. SII and PLR might help in further stratifying risk of recurrence when adopting the molecular risk-groups from ESGO-ESTRO-ESP-2021 guidelines. PLR≥250 surpassed ER, PR and p53 in conferring risk of recurrence.