The utility of post-TNT or post-TME ctDNA in guiding adjuvant therapy may be further enhanced by risk stratification based on the detection of specific driver mutations (e.g., TP53, KRAS) associated with higher rates of recurrence, as well as combined with clinicopathological features (e.g., perineural invasion, tumor deposits, vascular invasion, and lymph node metastasis) that altogether portend worsened outcomes [49, 59]. Here, KRAS is linked to metastatic malignant neoplasm in the lymph nodes.