Colorectal cancer remains one of the leading causes of cancer-related mortality worldwide, particularly at metastatic stage IV. Metastases most frequently develop in the liver, lungs, and peritoneum. Surgical resection of liver metastases offers a five-year survival rate of 50 to 60%, yet the disease recurs in up to 70% of patients who undergo such curative-intent resection. In this context, better assessing the risk of relapse based on pathomolecular and immune parameters represents a major clinical challenge. The consensus Immunoscore, a routine assay that quantifies the adaptive immune response within the tumor microenvironment by evaluating the infiltration of T lymphocytes and cytotoxic T lymphocytes, has already demonstrated its prognostic value in stages I, II, and III, as well as in resected metastases of stage IV patients.
The authors analyzed 582 metastases from 221 patients, following preoperative treatment and curative resection. For each sample, clinicopathological parameters, RAS mutational status, and the Immunoscore were evaluated, the latter being determined centrally to ensure analytical uniformity. Nearly all tumors were BRAF wild-type and microsatellite stable. In univariate analysis, several parameters were associated with a shorter time to relapse: lymph node involvement, the presence of more than three metastases (P = 0.0001), R1 resection margin, replacement or mixed histopathological growth patterns, and a low Immunoscore (P < 0.00001). In multivariate analysis, growth pattern, the presence of steatohepatitis, the number of resected metastases, margin status, and the Immunoscore were significantly associated with time to relapse, whereas only RAS mutation (P = 0.03) and the Immunoscore (P = 0.0009) remained associated with overall survival. To combine these factors, the team constructed a PathoScore (PS) integrating the clinicopathological parameters relevant to relapse. Patients with an unfavorable PS had a more than twofold higher risk of recurrence than those with a favorable PS (P < 0.00001). The Immunoscore remained the only parameter significant for both time to relapse and overall survival, with the highest relative contribution in both cases (30% and 64%, respectively). Independently of the PathoScore, patients with a high Immunoscore benefited from prolonged survival. The main acknowledged limitation lies in the retrospective nature of the study, which calls for further validation. These results confirm the clinical utility of the Immunoscore in stage IV patients, consistent with its integration into the 2020 ESMO guidelines and into the fifth edition of the WHO classification of tumors of the digestive system, which for the first time recognizes the immune response as an essential and desirable diagnostic criterion for colorectal cancer.