Game-score predicts pathological and radiological response to chemotherapy in patients with colorectal liver metastases

Background: Genetic And Morphological Evaluation (GAME) score is the newest prognostic model for patient with colorectal liver metastases (CRLMs). Pathological and radiological responses to neoadjuvant chemotherapy (NAC) can stratify the prognosis of these patients. Aim of the present study is to evaluate the ability of GAME score to predict pathological and radiologic responses to NAC. Methods: Patients with CRLMs who underwent liver resection after NAC between January 2010 and December 2021 were divided into three groups according to GAME scores: low risk (LR, 0–1), moderate risk (MR, 2–3), and high risk (HR, ≥4). Correlations between groups with radiological and pathological features were analyzed. Results: In total, 448 of the 1054 liver resections for CRLMs were included. GAME scores were grouped as follows: LR: 80 (18%), MR: 228 (51%), and HR: 140 (31%). HR-GAME scores were associated with lower pathological response assessed by Tumor Regression Grade 4–5 (LR: 67.1%, MR: 74.9%, HR: 82.6%; p=0.010). Radiologic progressive disease was found in 10% of HR patients, which was significantly higher than in the other groups (LR: 3.8%, MR: 3.5%; p=0.011). These findings were confirmed at multivariable analysis. HR-GAME scores were also associated with higher rates of mucinous differentiation (LR: 3.8%, MR: 8.8%, HR: 13.1%; p=0.021), satellitosis (LR: 27%, MR: 40.4%, HR: 53%; p=0.001), vascular invasion (LR: 73.8%, MR: 81%, HR: 87.5%; p=0.011), and perineural invasion (LR: 8.8%, MR: 10.6%, HR: 19.7%; p=0.010). Conclusions: GAME score category should be considered during planning of therapeutic strategy of patients with CRLMs.