Abstract
BACKGROUND: Adrenocortical carcinoma (ACC), an extremely uncommon and highly aggressive endocrine malignancy, has few therapeutic options and is associated with a poor prognosis. This study aimed to evaluate the prognostic significance of preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in a Chinese cohort with ACC and to determine the influence of cortisol secretion on these inflammatory markers. METHODS: We retrospectively analyzed 45 patients with ACC treated at a single institution from 1985 to 2020. Baseline clinicopathological data, preoperative NLR and PLR values, and follow-up information were collected. The NLR cutoff of 3.9 was selected a priori based on previously published studies of ACC. Disease-specific survival (DSS) was assessed via Kaplan-Meier and Cox proportional hazards models. Patients were stratified according to the presence of Cushing's syndrome (CS) in order to specifically assess the influence of hypercortisolemia. RESULTS: A total of 33 disease-specific deaths occurred during the follow-up period. Multivariate analysis indicated that the independent predictors of worse DSS were NLR >3.9 [hazard ratio (HR) =4.12, 95% confidence interval (CI): 1.25-13.61, P=0.02], an elevated Ki-67 index (HR =1.04, 95% CI: 1.01-1.07, P=0.01), and advanced European Network for the Study of Adrenal Tumors (ENSAT) stage (III-IV) (HR =45.64, 95% CI: 2.88-724.60, P=0.007). Although NLR was significantly higher in patients with CS than without CS (5.07 vs. 3.70, P=0.047), CS itself was not an independent prognostic factor. Notably, in patients without CS, elevated NLR correlated with aggressive features (local invasion, vascular invasion, and distant metastasis) but not with independent survival prognosis. CONCLUSIONS: Preoperative NLR >3.9 may serve as a simple and accessible prognostic marker for DSS in Chinese patients with ACC. Its predictive value is influenced by both tumor-induced inflammation and cortisol secretion, highlighting its utility in risk stratification beyond traditional factors.