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.