Resection of Colorectal Liver Metastasis: Prognostic Impact of Tumor Burden vs KRAS Mutational Status

Abstract

The prognostic impact of colorectal liver metastasis (CRLM) morphologic characteristics relative to KRAS mutational status after hepatic resection remains ill defined. Patients undergoing hepatectomy for CRLM between 2001 and 2018 were identified using an international multi-institutional database. Tumor burden score (TBS) was defined as distance from origin on a Cartesian plane that incorporated maximum tumor size (x-axis) and number of lesions (y-axis). Impact of TBS on overall survival (OS) relative to KRAS status (wild type [wtKRAS] vs mutated [mutKRAS]) was assessed. Among 1,361 patients, the median number of metastatic lesions was 2 (interquartile range [IQR] 1-3), and median size of the largest metastatic lesion was 3.0 cm (IQR 2.0-5.0 cm), resulting in a median TBS of 4.1 (IQR 2.8-6.1); KRAS status was wtKRAS (n= 420, 30.9%), mutKRAS (n= 251, 18.4%), and unknown (n= 690, 50.7%). Overall median and 5-year OS were 49.5 months (95%CI 45.2-53.8) and 43.2%, respectively. In examining the entire cohort, TBS was associated with long-term prognosis (5-year OS, low TBS: 49.4% vs high TBS: 36.7%), as was KRAS mutational status (5-year OS, wtKRAS: 48.2% vs mutKRAS: 31.1%; unknown KRAS: 44.0%)(both p < 0.01). Among patients with wtKRAS tumors, TBS was strongly associated with improved OS (5-year OS, low TBS: 59.1% vs high TBS: 38.4%, p= 0.002); however, TBS failed to discriminate long-term prognosis among patients with mutKRAS tumors (5-year OS, low TBS: 37.4% vs high TBS: 26.7%, p= 0.19). In fact, patients with high TBS/wtKRAS CRLM had comparable outcomes to patients with low TBS/mutKRAS tumors (5-year OS, 38.4% vs 37.4%, respectively; p= 0.59). On multivariable analysis, while TBS was associated with OS among patients with wtKRAS CRLM (hazard ratio 1.43, 95%CI 1.02-2.00; p= 0.03), TBS was not an independent predictor of survival among patients with mutKRAS CRLM (HR 1.36, 95%CI 0.92-1.99; p= 0.12). While TBS was associated with survival among patients with wtKRAS tumors, CRLM morphology was not predictive of long-term outcomes among patients with mutKRAS CRLM.