Multi‐instance learning for identifying high‐risk subregions associated with synchronous distant metastasis in clear cell renal cell carcinoma

Abstract Background Clear cell renal cell carcinoma (ccRCC) is one of the most common histological subtypes of renal tumors. Purpose To identify high‐risk subregions associated with synchronous distant metastasis. Methods This study enrolled a total of 277 patients with ccRCC. Voxel intensity and local entropy values were compiled within the region of interest for all patients. Unsupervised k ‐means clustering yielded three subregions per tumor. Radiomic features were extracted, and random forest‐based feature selection was conducted. The selected features were used in a multi‐instance support vector machine (mi‐SVM) model for training, and predictions were made on the validation cohort. Model performance was evaluated using five‐fold cross‐validation. The subregion with the highest score for patients with synchronous distant metastasis was identified across all cohorts. Results The mi‐SVM model yielded an average area under the curve (AUC) of 0.812 in the training cohort and 0.805 in the validation cohort. In the entire cohort of patients with synchronous distant metastasis, subregion 2, characterized by tumor periphery and intratumoral transitional components, accounted for the highest proportion (48.57%, 30.6/63) among all subregions. It represents a high‐risk subregion for synchronous distant metastasis of clear cell renal cell carcinoma. Conclusion The peripheral and intratumoral transition zones of clear cell renal cell carcinoma are high‐risk subregions associated with synchronous distant metastasis.