A Machine Learning Framework for Prognostic Modeling in Stage III Colon Cancer

Objective: To evaluate overall survival and to identify clinical, pathological, and demographic factors associated with survival in patients with stage III colon cancer. Methods: This retrospective cross-sectional study included 452 patients with stage III colon cancer who were followed at Ankara Bilkent City Hospital between 2005 and 2025. Patient data, including age, sex, ECOG performance status, comorbidities, tumor characteristics, treatment-related toxicities, and recurrence, were analyzed using PASW Statistics 18.0 (SPSS Inc., Chicago, IL, USA). Kaplan-Meier and log-rank tests were used for survival analysis. Prognostic factors, survival, mortality, and recurrence predictions were evaluated using machine learning algorithms, including coarse tree, bagged trees, support vector machines, and k-nearest neighbors. Furthermore, an explainable artificial intelligence framework was incorporated to improve model transparency and reveal clinically meaningful feature contributions. Model performance was assessed using accuracy, sensitivity, specificity, and F-score. Results: According to statistical analyses, older age, ECOG performance score ≥ 2, stage IIIC disease, N2-level lymph node metastasis, and the presence of comorbidities-particularly diabetes mellitus-were significantly associated with worse survival (p < 0.05). Machine learning analyses identified key prognostic factors, including positive surgical margins, rash, mucositis, thrombocytopenia, number of chemotherapy cycles, pathological tumor subtype, diarrhea, age at diagnosis, and anemia. SHAP analysis further demonstrated that treatment-related variables, particularly surgical margin positivity and chemotherapy-associated toxicities, were among the most influential predictors of survival. Several machine learning models outperformed traditional statistical methods in predicting mortality and recurrence, with the highest accuracy observed in ensemble methods such as coarse tree (87%) and bagged trees. Conclusions: This study identifies key prognostic factors influencing survival in stage III colon cancer and demonstrates that machine learning-based approaches can complement conventional statistical methods. The integration of clinical and treatment-related variables may improve individualized risk stratification and support clinical decision-making. These findings may also guide future large-scale, multicenter, and prospective studies.