Refining Tumor Response in Rectal Cancer: The Role of Tumor Budding

This thesis explores innovative approaches to evaluate response to neoadjuvant therapy in colorectal cancer, focusing on tumor budding (TB) as a predictive biomarker. We examined TB and tumor-infiltrating lymphocytes (TILs) as opposing forces in the tumor microenvironment, emphasizing their prognostic significance. Recognizing the limitations of current response assessment methods, we introduced a novel classification of tumor response patterns—fragmentation and shrinkage—demonstrating that fragmentation is associated with poorer outcomes. We then investigated lymph node metastases (LNM), showing that a pathological complete response occurs more frequently in LNM than in the primary tumor. That response in LNM is associated with improved survival. Finally, we assessed intratumoral budding (ITB) in diagnostic biopsies using computational pathology. ITB proved to be an independent prognostic factor and a reliable biomarker for predicting complete response to therapy. Together, these findings contribute to a more nuanced understanding of therapy response in colorectal cancer and offer promising tools for personalized treatment strategies.