A liver-first surgical approach in stage IV colorectal cancer with isolated liver metastases leads to better survival and fewer complications.

• Liver resection before colon/rectal resection increased from 5.37% in 2010 to 15.43% in 2020.
• Patients receiving the liver-first approach had a lower 90-day mortality (1.11% vs 4.47%) and fewer 30-day readmissions (3.69% vs 5.81%).

Select patients with rectal primaries at academic centers may benefit most, improving surgical outcomes significantly.

• Better overall survival rates were noted for the liver-first approach (hazard ratio, 0.87).