Ki-67 as a Predictor of Metastasis in Adrenocortical Carcinoma: Artificial Intelligence Insights from Retrospective...

Background/Objectives: Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with poor prognosis, particularly in metastatic cases. The Ki-67 proliferation index is a recognized marker of tumor aggressiveness, yet its role in guiding diagnostic imaging and surgical decision-making remains underexplored. This study evaluates Ki-67's predictive value for metastasis at diagnosis, leveraging artificial intelligence (AI) to inform personalized, minimally invasive strategies for ACC management. Methods: We retrospectively analyzed 53 patients with histologically confirmed ACC from the Adrenal-ACC-Ki67-Seg dataset in The Cancer Imaging Archive. All patients had Ki-67 indices from surgical specimens and preoperative contrast-enhanced CT scans. Descriptive statistics, t-tests, ANOVA, and multivariable logistic regression evaluated associations between Ki-67, tumor size, age, and metastasis. Random Forest classifiers-with and without the Synthetic Minority Oversampling Technique (SMOTE)-were developed to predict metastasis. A Ki-67-only model served as a baseline comparator. Model performance was assessed using the area under the curve (AUC) and DeLong's test. Results: Patients with metastatic disease had significantly higher Ki-67 indices (mean 39.4% vs. 21.6%, p < 0.05). Logistic regression identified Ki-67 as the sole significant predictor (OR = 1.06, 95% CI: 1.01-1.12). The Ki-67-only model achieved an AUC of 0.637, while the SMOTE-enhanced Random Forest achieved an AUC of 0.994, significantly outperforming all others (p < 0.001). Conclusions: Ki-67 is significantly associated with metastasis at ACC diagnosis and demonstrates independent predictive value in regression analysis. However, integration with machine learning models incorporating tumor size and age significantly improves overall predictive accuracy, supporting AI-assisted risk stratification and precision imaging strategies in adrenal cancer care.