Current perspectives and guidelines on liver transplantation for metastatic colorectal cancer

Table 2 Trials covering liver transplantation outcomes in patients with metastatic colorectal cancer

Trial	Country	Type of study	Oncological criteria/design	Primary outcomes	Secondary outcomes
Transmet	France	Multicentric phase III RCT randomized, controlled	Primary tumour resection according to oncological principles; BRAF non-mutated; CRLM definitively unresectable according to multidisciplinary panel expert; ≤ 3 chemotherapy lines for metastatic disease; Stable disease (RECIST criteria) on chemotherapy > 3 months; CEA level < 80 μg/L or at least 50% decrease of maximal level; No extrahepatic disease confirmed by CT and PET/CT	OS at 5 years	OS at 3 years, DFS, PFS, recurrence, QOL
SECA III	Norway	Randomized, controlled	LT vs other treatment options including chemotherapy, TACE, or SIRT	OS at 2 years	None listed
Soulmate	Sweden	Randomized, controlled	LT from extended criteria donors + best-established treatment (BET) vs BET alone	OS at 5 years	OS at 2 years, median OS, PFS, recurrence-free survival, QOL, QALY
Excalibur 1	Norway	Randomized, controlled	LT + chemotherapy vs HAI/FUDR + chemotherapy vs chemotherapy alone	OS at 2 years	QOL, 30-/90-day morbidity/mortality
Colt	Italy	Nonrandomized, prospective	LT vs triplet chemotherapy + anti-EGFR	OS at 5 years	PFS, complications
Melodic	Italy	Nonrandomized, prospective	LT vs chemotherapy	OS at 3 years, OS at 5 years	PFS, dropouts, complications
Livermore	Italy	Single group, open label	LDLT vs historical cohort of potentially transplantable patients who received chemotherapy only	OS at 5 years, DFS at 5 years	Graft survival, donor QOL
Litorale 2020	Italy	Single group, open label	LT	OS at 5 years	DFS
NCT04874259	Korea	Single group, open label	LDLT	OS at 1 year	DFS, OS at 3 years, recurrence
Livert(w) o heal	Germany	Single group, open label	LDLT with two-staged hepatectomy vs historic cohort of patients who received gold-standard chemotherapy	OS at 3 years	DFS, morbidity of recipient, morbidity of donor
RAPID-Padova	Italy	Single group, open label	LT with staged hepatectomy	Percent of patients receiving hepatectomy within 4 weeks of transplant	OS, PFS, dropouts, mortality, complications
Trasmetir	Spain	Cohort, prospective	LT	OS at 5 years	DFS, QOL
NCT02864485	Canada	Single group, open label	Primary CRC tumour stage ≤ T4a; BRAF non-mutated; Bilateral and non-resectable CRLM without major vascular invasion by LM; Time from primary CRC resection to transplant is ≥ 6 months; No extra hepatic disease; Preoperative systemic chemotherapy for ≥ 3 months; Stable disease on chemotherapy > 3 months; CEA values are stable or decreasing at all timepoints; LDLT vs patients who drop out prior to transplantation	OS at 5 years, DFS at 5 years	Recurrence, types of cancer recurrence treatments, dropouts, QOL, OS/DFS at 1 and 3 years
Metliver	Spain	Single group, open label	LT	OS at 5 years	OS at 1 and 3 years, recurrence-free survival, dropouts, recurrence, QOL
NCT06069960	China	Single group, open label	Hemihepatectomy with concurrent left lateral lobe LT followed by delayed residual liver resection	OS at 3 years post second liver resection	DFS
RAPID 2014	Norway	Single group, open label	Unresectable liver metastases technically; Maximal size of CRLM < 10 cm and total number < 20; CEA < 100 ng/mL at time of diagnosis; Standard surgical procedure with adequate resection; pN0 primary tumour as pN0; No extra hepatic disease confirmed by CT and PET/CT, except patients may have 1-3 resectable lung lesions all < 15 mm; At least 8 weeks of chemotherapy; Liver segmentectomy with concurrent left lateral lobe LT followed by delayed residual liver resection	Percent receiving second-stage hepatectomy within 4 weeks	OS

LT: Liver transplantation; OS: Overall survival; DFS: Disease-free survival; PFS: Progression-free survival; QOL: Quality of life; TACE: Transarterial chemoembolization; SIRT: Selective internal radiation therapy; QALY: Quality-adjusted life years; HAI/FUDR: Hepatic arterial infusion with floxuridine; CT: Computed tomography; CRLM: Colorectal liver metastasis; CEA: Carcinoembryonic antigen; LDLT: Living donor liver transplant.