A multimodal ensemble approach for clear cell renal cell carcinoma treatment outcome prediction.

Purpose: A reliable cancer prognosis model for clear cell renal cell carcinoma (ccRCC) can enhance personalized treatment. We developed a multi-modal ensemble model (MMEM) that integrates pretreatment clinical data, multi-omics data, and histopathology whole slide image (WSI) data to predict overall survival (OS) and disease-free survival (DFS) for ccRCC patients. Methods: We analyzed 226 patients from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) dataset, which includes OS, DFS follow-up data, and five data modalities: clinical data, WSIs, and three multi-omics datasets (mRNA, miRNA, and DNA methylation). Separate survival models were built for OS and DFS. Cox-proportional hazards (CPH) model with forward feature selection is used for clinical and multi-omics data. Features from WSIs were extracted using ResNet and three general-purpose foundation models. A deep learning-based CPH model predicted survival using encoded WSI features. Risk scores from all models were combined based on training performance. Results: Performance was assessed using concordance index (C-index) and AUROC. The clinical feature-based CPH model received the highest weight for both OS and DFS tasks. Among WSI-based models, the general-purpose foundation model (UNI) achieved the best performance. The final MMEM model surpassed single-modality models, achieving C-indices of 0.820 (OS) and 0.833 (DFS), and AUROC values of 0.831 (3-year patient death) and 0.862 (cancer recurrence). Using predicted risk medians to stratify high- and low-risk groups, log-rank tests showed improved performance in both OS and DFS compared to single-modality models. Conclusion: MMEM is the first multi-modal model for ccRCC patients, integrating five data modalities. It outperformed single-modality models in prognostic ability and has the potential to assist in ccRCC patient management if independently validated.