Multi-Model Machine Learning for Survival Predictions for Castration-Resistant Prostate Cancer.

Background: Accurate survival prediction is essential for optimizing treatment planning in patients with castration-resistant prostate cancer (CRPC). However, traditional statistical models often underperform because of limited variable inclusion and an inability to account for complex, multidimensional data interactions. Methods: We retrospectively collected 46 clinical, laboratory, and pathological variables from 801 patients with CRPC, covering the disease course from initial diagnosis to CRPC progression. Multiple machine learning (ML) models, including random survival forests (RSF), XGBoost, LightGBM, and logistic regression, were developed to predict cancer-specific mortality (CSM), overall mortality (OM), and 2- and 3-year survival status. The dataset was divided into training and test cohorts (80:20), and 10-fold cross-validation was performed. Performance was assessed using the C-index for regression models and the area under the curve (AUC), accuracy, precision, recall, and F1-score for classification models. Model interpretability was evaluated using SHapley Additive exPlanations (SHAP). Results: Over a median follow-up of 24 months, 70.6% of patients experienced CSM. Although XGBoost with its own imputation method achieved the highest C-index in the validation set, RSF demonstrated more stable performance and achieved the highest C-index in the held-out test set for both CSM (0.772) and OM (0.771). For classification tasks, RSF demonstrated superior performance in predicting 2-year survival, whereas XGBoost achieved the highest F1-score for 3-year survival prediction. SHAP analysis identified time to first-line CRPC treatment, hemoglobin level, and alkaline phosphatase level as key predictors of survival outcomes. Conclusions: RSF demonstrated robust test-set performance for time-to-event prediction, whereas XGBoost showed complementary value for 3-year survival classification. These models provide accurate and interpretable prognostic tools that may support personalized treatment strategies. External validation and integration of emerging therapies are warranted to enhance broader clinical applicability.