Resectability assessment: shifted from morphologic (number, size, location) to oncologic + technical criteria. Resectable - all disease can be removed with negative margins (R0) preserving ≥30% functional liver remnant (FLR) with adequate inflow, outflow, and biliary drainage. Borderline/unresectable - inadequate FLR, multiple bilobar disease, vascular involvement requiring complex reconstruction, extrahepatic disease (resectable lung mets allowed in select cases). Imaging - contrast-enhanced CT (chest/abdomen/pelvis), MRI liver with hepatocyte-specific contrast (gadoxetate/Eovist) for small lesions, FDG-PET for extrahepatic disease, intraoperative ultrasound (IOUS) for additional lesion detection. Mutational profiling - RAS, BRAF, MSI status guides systemic therapy selection.
Surgical strategies: 1) Anatomic resection (right/left hepatectomy, sectionectomy) - preferred for hilar lesions with vascular invasion; 2) Parenchymal-sparing surgery (PSS) - non-anatomic wedge resections, preserves FLR, allows future re-resection of recurrence; 3) Two-stage hepatectomy - clear left hemiliver of metastases first → PVE → right hepatectomy 4-8 weeks later when right FLR insufficient; 4) ALPPS (Associating Liver Partition with Portal vein ligation for Staged hepatectomy) - rapid hypertrophy in 7-14 days, technically challenging, mortality 5-10%; 5) Portal vein embolization (PVE) - induces compensatory hypertrophy of contralateral lobe, 4-8 week interval; 6) Combined liver-colorectal resection (synchronous strategy) - simultaneous or staged; 7) Liver-first approach - reverse strategy in selected cases.
Multimodal management: 1) Neoadjuvant chemotherapy - FOLFOX or FOLFIRI ± bevacizumab (RAS-agnostic) or cetuximab/panitumumab (RAS WT) for 4-6 cycles in upfront resectable, 8-12 cycles in borderline cases; assess response by RECIST and reduce duration to minimize hepatotoxicity (CASH - chemotherapy-associated steatohepatitis with irinotecan; SOS - sinusoidal obstruction syndrome with oxaliplatin); 2) Adjuvant chemotherapy - FOLFOX or capecitabine 6 months post-resection; 3) Hepatic arterial infusion (HAI) chemotherapy - select centers, FUDR via implanted pump; 4) Ablation (RFA, MWA) - lesions <3 cm not amenable to resection, can combine with surgery; 5) Stereotactic body radiation therapy (SBRT) - for non-surgical candidates; 6) Liver transplantation - select unresectable patients (SECA, TRANSMET trials, oligometastatic, RAS WT). Outcomes - R0 resection 5-year survival 30-50%, 10-year 20-25%; recurrence 60-70% (intrahepatic 50%, extrahepatic 30%).