TRANsplantation vs reSECTion After Conversion Therapy for Initially Unresectable Colorectal Liver Metastases

Inclusion Criteria screening phase (before randomization): * Signed screening phase informed consent. * Age \>18. * Performance status score of Eastern Cooperative Oncology Group (PS-ECOG) 0-1 * Adequate organ functions. * Liver-limited Metastatic Disease Confirmed as Unresectable by Colorectal Oncology Multidisciplinary Tumor Board (MTB). * Histologically documented adenocarcinoma of the colon or intra-peritoneal rectum * Absence of extra-hepatic disease demonstrated by contrast-enhanced CT + MRI and, in clinically indicated (clinical suspicion or elevated biomarkers), FDG-PET. * No previous systemic treatment for unresectable disease. * No previous systemic treatment for primary tumor resection * Recurrence occurring beyond six months after completion of adjuvant treatment. * MMR proficient cancer (MSS) regardless of RAS mutational status, BRAF-WT except for BRAF V600E-mut treated and responding to anti-BRAF + cytotoxic therapy. Exclusion criteria: * Absolute contraindication to liver transplant. * Other malignancies in the previous 5 years excluding non melanoma skin-cancers or in situ disease. * Hereditary CRC syndromes including FAP and Lynch syndrome. * Previous extrahepatic metastatic localization or locoregional tumor recurrence. * Extra-peritoneal cancers. * BRAFV600E-mut patients non-responder to 1st line anti-BRAF + cytotoxic therapy (Elez et al NEJM 2025, ref. 8) Randomization inclusion criteria: * Signed randomization phase informed consent. * CEA \< 80 ng/ml or decrease in CEA level at least 50% from baseline (TRANSMET criteria (5)). * Conversion to resectability according to MTB discussion during first 6 months of induction chemotherapy. * Sustained objective response defined as stable disease (SD), partial response (PR) or complete response (CR) according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria (19), under chemotherapy, for at least 3 months. * Surgical resection of the primary tumor with a high oncological standard, as outlined in The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Colon Cancer (20), ensuring safe margins of resection and adequate TNM staging. * Histologically confirmed primary tumor with achievement of R0 resection. * Three months interval from primary tumor resection to randomization in patients staged up to pT3b and pN1. * Only metachronous metastases are eligible in pT4a and/or pN2 primary. For pT4a tumors, a minimum disease-free interval of 6 months from primary tumor resection is required before randomization. * Absence of local recurrence and extra-hepatic disease demonstrated by contrast-enhanced CT + MRI and, in clinically indicated (clinical suspicion or elevated biomarkers), FDG-PET. * PS-ECOG 0-1. * Adequate organ functions.