Tumor-size responses to first-line is a predictor of overall survival in metastatic colorectal cancer.

• Early shrinking tumors under first-line chemotherapy responded better to subsequent lines, maintaining low tumor loads, potentially explaining the link between early tumor shrinkage and overall survival of metastatic colorectal cancer (mCRC) patients. • mCRCs progressing under first-line chemotherapy remained refractory to other therapies and their tumor loads increased rapidly. • Even outside a clinical trial, an early first CT scan reevaluation with RECIST criteria 8 weeks after starting first-line therapy is crucial to determine long-term mCRC evolution.