Artificial intelligence morphology and host complexity for precision prediction of nodal metastasis in colorectal cancer

Table 3 Potential clinical implications of extending the multiple instance learning-based prediction model by Zou et al[6] into a multimodal framework

Clinical domain	Current practice limitation	Multimodal model contribution	Resulting clinical implication
Extent of mesenteric excision (CME/TME)	Surgical extent often based on morphology, experience, and imaging; variable across centers	Multimodal LNM prediction integrates AI pathology + clinical context + host complexity	Individualized mesenteric resection plans based on quantified metastatic propensity
Neoadjuvant therapy selection	Decisions rely on TNM stage and imaging; occult LNM risk underestimated	Model identifies biologically high-risk patients despite imaging-negative nodes	Supports escalation or de-escalation of neoadjuvant therapy
Adjuvant therapy tailoring	Stage-based decision often leads to overtreatment or undertreatment	Multimodal risk category reflects recurrence-related biology	Enables precision adjuvant chemotherapy decisions
Perioperative host optimization	Limited integration of inflammation, nutrition, circadian, or autonomic markers	Host systemic complexity identifies modifiable vulnerabilities (IL-6, CRP, HRV, metabolic reserve)	Personalized interventions (sleep, nutrition, autonomic regulation, anti-inflammatory strategies)
Surveillance strategy	Follow-up schedules are stage-based and uniform	Multimodal outputs yield individualized recurrence risk	Allows dynamic, risk-adaptive surveillance intensity
Patient counseling and shared decision-making	Risk discussions often nonspecific	Clear risk categories + uncertainty quantification	Improves informed decision-making

The clinical pathways incorporate the morphologic risk signals derived from the multiple instance learning model reported by Zou et al[6] and extend them through integration with host systemic complexity and clinical contextual variables. AI: Artificial intelligence; CME: Complete mesocolic excision; TME: Total mesorectal excision; HRV: Heart rate variability; CRP: C-reactive protein; IL-6: Interleukin-6; TNM: Tumor-node-metastasis; LNM: Lymph node metastasis.