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

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.

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.

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).

In patients with CLM with higher disease burden, FOLFOXIRI may be preferable to FOLFOX/FOLFIRI for preoperative chemotherapy.