Enhancing outcome prediction in patients with colorectal liver metastases undergoing hepatectomy: the synergistic impact of FIB-4 index and tumor burden score across KRAS profiles

Background: The prognostic value of Fibrosis-4 (FIB-4) index, concerning KRAS status (wild-type [wtKRAS] vs. mutated [mutKRAS]) remains unclear in post-hepatectomy colorectal liver metastases (CRLM). We evaluated the combined impact of FIB-4 and Tumor Burden Score (TBS) on overall survival (OS)/recurrence-free survival (RFS), stratified by KRAS status. Methods: CRLM patients undergoing hepatectomy (2000-2020) were analyzed, grouped by TBS/FIB-4. Results: Among 828 patients, 196 had high FIB-4. High TBS had worse 5-year OS (P < 0.001). In wtKRAS, high TBS correlated with worse OS (P < 0.001), but not in mutKRAS. High FIB-4 correlated with worse OS (P = 0.01). Sub-stratification showed no OS difference by FIB-4 in wtKRAS, but a difference in mutKRAS (P = 0.03). Multivariable analysis identified mutKRAS (HR: 1.90), high TBS (HR: 1.62), and FIB-4 (HR: 1.15) as mortality risk factors. The TBS-FIB-4-KRAS index had highest predictive accuracy. For RFS, TBS and FIB-4 independently stratified outcomes. High TBS was associated with worse RFS in wtKRAS (P < 0.001) but not in mutKRAS. High FIB-4 decreased RFS in mutKRAS (P = 0.001) but not in wtKRAS. FIB-4 was associated with a 10% increased recurrence risk. Conclusion: TBS and FIB-4, alongside KRAS status, should be considered to improve outcome predictions.