Histology-specific prognostic significance of isolated tumor cells, micrometastases, and macrometastases in endometrial cancer.

Objective: To examine the association between regional lymph node status based on metastatic size and anatomical location and survival per histology in endometrial cancer.

Methods: This retrospective study queried the Commission-on-Cancer's National Cancer Database. Study population included 87,904 patients with stage I-III endometrial cancer from 2018 to 2021. Multivariable Cox proportional hazard regression models were created to assess overall survival per histology (non-endometrioid / high-grade endometrioid or low-grade endometrioid).

Results: In both histology groups, comparing to pelvic micro-metastasis, macro-metastasis regardless of anatomical location (pelvic / para-aortic) was associated with decreased overall survival (non-endometrioid / high-grade endometrioid histology, adjusted-hazard ratio [aHR] 1.31, 95% confidence interval [CI] 1.08-1.59/aHR 1.39, 95%CI 1.13-1.72; and low-grade endometrioid histology, aHR 1.68, 95%CI 1.19-2.36 / aHR 1.78, 95%CI 1.10-2.88) while para-aortic micro-metastases had overall survival similar to pelvic micro-metastasis. Survival effects of macro-metastasis were larger in low-grade endometrioid compared to non-endometrioid / high-grade endometrioid histology (aHR range, 1.68-1.78 vs 1.31-1.39). For non-endometrioid / high-grade endometrioid histology, isolated tumor cells were associated with better overall survival compared to pelvic micro-metastasis (aHR 0.62, 95%CI 0.45-0.85); isolated tumor cells and negative nodal metastasis had similar overall survival (aHR 1.05, 95%CI 0.80-1.38). Contrary, in low-grade endometrioid histology, isolated tumor cells were associated with decreased overall survival compared to negative-node (aHR 1.55, 95%CI 1.18-2.04); isolated tumor cells had overall survival similar to pelvic micro-metastasis (aHR 0.83, 95%CI 0.56-1.24).

Conclusion: The results of this cohort study suggest that tumor metastatic size may be more prognostic than anatomical location in endometrial cancer. Histology-specific interaction of isolated tumor cells warrants further investigation, especially in low-grade endometrioid histology.