The effect of para-aortic lymphadenectomy on survival in early stage endometrioid grade 3 and non-endometrioid endometrial cancers.

BACKGROUND: The prognostic and therapeutic significance of para-aortic lymphadenectomy remains controversial due to conflicting evidence in the literature. There are limited studies specifically examining patients with grade 3 endometrioid and non-endometrioid histologies. In this study, we aimed to investigate the effect of adding para-aortic lymphadenectomy to pelvic lymphadenectomy on survival outcomes in patients with early-stage uterine-confined grade 3 endometrioid and non-endometrioid endometrial carcinoma. METHODS: This retrospective cohort study included 182 patients with FIGO 2009 stage I-II, pathologically node-negative grade 3 endometrioid or non-endometrioid endometrial cancers treated at a single tertiary center between 1995 and 2025. Patients underwent either pelvic lymphadenectomy (PLND) alone 85 (46.7%) or combined pelvic and para-aortic lymphadenectomy (PPLND) 97 (53.3%). Clinicopathological data and survival outcomes were compared. Kaplan-Meier survival curves, log-rank tests, and Cox proportional hazards models were used to assess disease-free survival (DFS) and overall survival (OS). RESULTS: The median duration of follow-up in the overall cohort was 60.5 months, while the median time to recurrence among patients who experienced disease relapse was 52.0 months. No significant difference was observed in DFS or OS between patients who underwent PLND alone and those who underwent PPLND. The hazard ratio (HR) for DFS was 0.88 (95% CI: 0.47-1.64, p = 0.690), and similarly, the HR for OS was 0.98 (95% CI: 0.60-1.62, p = 0.941). In univariate and multivariate Cox regression analysis, non-endometrioid histology was associated with worse DFS and OS (p:<0.001, p:0.04). While there was no significant difference in DFS in patients aged ≥ 60 years, a three-fold worse OS outcome was found (HR = 3.08; 95% CI: 1.59-5.99; p < 0.001). Other clinicopathological parameters, such as FIGO stage, depth of myometrial invasion, presence of lymphovascular invasion (LVSI), cytology results, surgical approach, and extent of lymphadenectomy, did not show a significant association with DFS or OS in multivariate analysis (all p > 0.05). CONCLUSIONS: In patients with early-stage, node-negative grade 3 endometrioid and non-endometrioid endometrial cancers, the addition of para-aortic lymphadenectomy to pelvic dissection did not confer a survival advantage. Moreover, older age (≥ 60 years) was associated with significantly worse overall survival.