Prognostic value of primary tumor site in surgery for colorectal liver metastases

Table 1 Evolving paradigms in the management of colorectal liver metastases

Principle	Traditional paradigm	New, biology-driven paradigm
Defining logic	Technical resectability of metastatic disease	Inherent biological aggressiveness of the primary tumor
Central prognostic factor	Metastatic burden (number and size of lesions)	Primary tumor location and its associated biologic phenotype
Role of primary tumor	Historical point of origin	Key regulator of metastatic behavior and host systemic response
Therapeutic goal	Standardised application guidelines	Risk-adapted site-specific intensification of multimodal therapy
Implied action	Uniform treatment protocols	Location-defined and molecular-informed treatment algorithms

Table 2 The clinical and biologic profile of right-sided colorectal liver metastases

Clinical domain	Manifestations in right-sided CRLM[1]	Proposed biological driver	Actionable clinical response
Metastatic aggression	High lymph node metastasis rate; > 55% 12-month recurrence	CMS4 mesenchymal phenotype; enhanced invasive capacity	Enhanced staging; pursuit of wider surgical margins
Systemic environment	Elevated D-dimer; hypoalbuminemia	Tumor-induced hypercoagulability; cancer-associated systemic inflammation	Consider perioperative anticoagulation; mandatory prehabilitation
Therapeutic resistance	High rate of poor neoadjuvant response	Distinct molecular drivers (e.g., BRAF); enriched chemoresistant pathways	First-line therapy intensification; early biomarker integration
Ultimate outcome	Diminished median overall survival	Synergistic effect of an aggressive biologic phenotype	Classify as “ultra-high risk”; implement intensive, personalised surveillance

CRLM: Colorectal liver metastases; CMS4: Consensus molecular subtype 4; BRAF: V-Raf murine sarcoma viral oncogene homolog B.