Short- and Long-Term Outcomes After Hepatectomy in Patients Receiving Triplet Versus Doublet Preoperative Chemotherapy for Colorectal Liver Metastases

Background: FOLFOXIRI is associated with better response and higher resection rates than doublet regimens for colorectal liver metastases (CLM); however, irinotecan and oxaliplatin may cause liver injury, increasing the risk of hepatectomy. This study compared outcomes between patients receiving FOLFOXIRI versus FOLFOX/FOLFIRI before undergoing CLM resection. Methods: This multicenter retrospective study included consecutive patients undergoing CLM resection during 2010–2021 after preoperative FOLFOXIRI or FOLFOX/FOLFIRI as first-line chemotherapy. Patients receiving multiple lines of therapy were excluded. Results: Of 1711 patients included, 160 (9.4%) received FOLFOXIRI and 1551 (90.6%) received FOLFOX/FOLFIRI. Patients receiving FOLFOXIRI were younger (median age 55 vs. 59 years; p < 0.001), had a higher rate of synchronous CLM (93.7% vs. 78.7%; p < 0.001), and had a higher median tumor burden score (TBS; 5.6 vs. 4.1; p < 0.001). In both groups, a median of six cycles of preoperative chemotherapy were administered. Outcomes after FOLFOXIRI (vs. FOLFOX/FOLFIRI) were as follows: major hepatectomy, 44.4% of patients (vs. 35.3%; p = 0.024), median estimated blood loss, 300 mL (vs. 200 mL; p = 0.006), rate of intraoperative blood transfusion, 8.1% (vs. 4.4%; p = 0.034), 90-day major complication rate, 13.3% (vs. 10.0%; p = 0.193), 90-day mortality rate, 1.2% (vs. 0.6%; p = 0.324), and 5-year overall survival (OS) rate, 66.6% (vs. 56.4%; p = 0.072). Medium–high TBS, synchronous extrahepatic disease, positive resection margin, and RAS mutation were independent risk factors for poor OS. Patients with medium–high TBS had a significantly better 5-year OS rate after FOLFOXIRI than after FOLFOX/FOLFIRI (67.6% vs. 50.1%; p = 0.004). Conclusion: In patients with CLM with higher disease burden, FOLFOXIRI may be preferable to FOLFOX/FOLFIRI for preoperative chemotherapy.