Comprehensive characterisation of patients with colorectal cancer and permanently liver-limited disease

Background Metastatic colorectal cancer (mCRC) shows organ-specific patterns of dissemination. Approximately 20% of patients develop disease confined to the liver throughout the course. Early recognition and characterisation of this phenotype may inform therapeutic stratification and improve outcomes. Patients and methods We retrospectively analysed patients with unresectable mCRC. Patients were classified by metastatic distribution into liver-limited, liver plus extrahepatic, or extrahepatic-only disease. Clinicopathological features, genomic alterations assessed by next-generation sequencing, and immune contexture based on a 12-gene signature from the primary tumour were evaluated. Results Among 1026 eligible patients, 20% had permanently liver-limited disease, 51% had both hepatic and extrahepatic involvement, and 29% had extrahepatic-only metastases. Liver-limited cases were enriched for synchronous presentation and nonrectal primaries, with a lower prevalence of KRAS mutations ( P = 0.013). Tumours with liver plus extrahepatic dissemination showed greater genetic alterations across multiple cancer hallmarks ( P < 0.05). Immune profiling revealed a markedly lower proportion of cold phenotypes in extrahepatic-only disease compared with liver-involved cases ( P = 0.041). Despite similar genomic profiles, extrahepatic-only disease was associated with improved overall survival. Conclusions Permanent liver-limited mCRC defines a clinically and biologically distinct subgroup characterised by synchronous onset, nonrectal primaries, and reduced KRAS mutation frequency. The immune landscape of the primary tumour was associated with metastatic organ pattern.