Colorectal cancer is among the leading causes of cancer-related mortality worldwide, and its prognosis worsens markedly in the presence of metastases, particularly hepatic ones. Surgical resection of liver metastases, combined with systemic treatment, offers selected patients a five-year survival rate of around 50–60%. However, recurrence remains very common: it occurs in up to 70% of patients undergoing curative-intent surgery, and approximately half relapse within the first two years following hepatectomy. Identifying patients at high risk of recurrence at an early stage is therefore a major clinical challenge, which requires consensus-based, well-characterized biomarkers.
To address this question, the authors conducted a retrospective analysis of 221 patients who underwent curative resection of 582 metastases, following various preoperative treatments. Each surgical specimen was evaluated using an integrated assessment combining clinicopathological parameters, the tumor RAS mutational status, and the consensus Immunoscore, which quantifies tumor infiltration by T and cytotoxic T lymphocytes. Overall survival and time to relapse were estimated using the Kaplan-Meier method, and prognostic factors were analyzed using Cox models in univariate and multivariate analyses.
In multivariate analysis, the Immunoscore and several clinicopathological parameters—number of metastases, surgical margin, histopathological growth pattern, and steatohepatitis—were associated with relapse. Based on the most relevant factors, the authors constructed a combined pathological score. This score and the Immunoscore proved prognostic for time to relapse: the two-year relapse rate reached 20.9% for an unfavorable pathological score (2–4) versus 49.8% for a favorable score (0–1); it was 25.7% for a null Immunoscore versus 60% for a high Immunoscore (3–4). The Immunoscore also remained the major determinant of overall survival, with mutated RAS status contributing more modestly. Patients combining a favorable pathological score and a high Immunoscore had the lowest risk of relapse.
The authors emphasize that steatohepatitis, an important contributor to the pathological score, proved to be of poor prognosis regardless of its origin, with no association with irinotecan but rather with metabolic syndrome or obesity. They also note that pathological response, which is usually prognostic in treated patients, lost its significance in this unselected cohort regardless of the preoperative treatment. The main limitation remains the retrospective nature of the study, warranting further validation work. In conclusion, comprehensive pathological and immune assessment of the metastasis and surrounding liver parenchyma allows prognostic stratification of patients with stage IV colorectal cancer, with the combination of the pathological score and the Immunoscore aiding clinical decision-making after resection, the Immunoscore remaining the key determinant of overall survival.