Recipient and Donor Outcomes After Living-Donor Liver Transplant for Unresectable Colorectal Liver Metastases

Question  What are the estimated overall and recurrence-free survival outcomes after living-donor liver transplant (LDLT) in patients with liver-confined, unresectable colorectal cancer liver metastasis (CRLM)?

Findings  In this cohort study of 10 adults with CRLM who received LDLT, Kaplan-Meier estimates of recurrence-free and overall survival at a median follow-up of 1.5 years were 62% and 100%, respectively. Perioperative outcomes for both recipients and donors were consistent with established benchmarks.

Meaning  The results suggest that LDLT may be a viable treatment option for select patients with unresectable CRLMs with favorable tumor biology.

Importance  Colorectal cancer is a leading cause of cancer-related death, and nearly 70% of patients with this cancer have unresectable colorectal cancer liver metastases (CRLMs). Compared with chemotherapy, liver transplant has been reported to improve survival in patients with CRLMs, but in North America, liver allograft shortages make the use of deceased-donor allografts for this indication problematic.

Objective  To examine survival outcomes of living-donor liver transplant (LDLT) for unresectable, liver-confined CRLMs.

Design, Setting, and Participants  This prospective cohort study included patients at 3 North American liver transplant centers with established LDLT programs, 2 in the US and 1 in Canada. Patients with liver-confined, unresectable CRLMs who had demonstrated sustained disease control on oncologic therapy met the inclusion criteria for LDLT. Patients included in this study underwent an LDLT between July 2017 and October 2020 and were followed up until May 1, 2021.

Exposures  Living-donor liver transplant.

Main Outcomes and Measures  Perioperative morbidity and mortality of treated patients and donors, assessed by univariate statistics, and 1.5-year Kaplan-Meier estimates of recurrence-free and overall survival for transplant recipients.

Results  Of 91 evaluated patients, 10 (11%) underwent LDLT (6 [60%] male; median age, 45 years [range, 35-58 years]). Among the 10 living donors, 7 (70%) were male, and the median age was 40.5 years (range, 27-50 years). Kaplan-Meier estimates for recurrence-free and overall survival at 1.5 years after LDLT were 62% and 100%, respectively. Perioperative morbidity for both donors and recipients was consistent with established standards (Clavien-Dindo complications among recipients: 3 [10%] had none, 3 [30%] had grade II, and 4 [40%] had grade III; donors: 5 [50%] had none, 4 [40%] had grade I, and 1 had grade III).

Conclusions and RelevanceThis study’s findings of recurrence-free and overall survival rates suggest that select patients with unresectable, liver-confined CRLMs may benefit from total hepatectomy and LDLT.

This cohort study found that selected patients with unresectable, liver-confined CRLMs may benefit from total hepatectomy and LDLT, with encouraging rates of recurrence-free and overall survival. Unresectable CRLMs with favorable tumor biology may become an acceptable indication for LT. Careful patient selection remains the key for ensuring acceptable oncologic outcomes for this disease. As more centers begin to use this novel treatment approach, prospective multicenter collaborations must be established to continue to understand and refine the selection and treatment-response criteria. It is time for a North American registry for centers performing LT for unresectable CRLMs. Such a registry will provide a platform for data acquisition in what remains a rare indication for LT, and it may improve understanding of gaps in treatment and of the natural history of posttransplant recurrence and survival. However, LT for CRLMs should be adopted with great caution and only by centers with experienced multidisciplinary teams that include gastrointestinal oncology, transplant oncology, hepatobiliary surgery, and liver transplant. The field of transplant oncology should move toward unified criteria that may facilitate the incorporation of selected patients with CRLMs into the standard organ-allocation systems.

Accepted for Publication: January 9, 2022.

Published Online: March 30, 2022. doi:10.1001/jamasurg.2022.0300

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Hernandez-Alejandro R et al. JAMA Surgery.

Corresponding Author: Gonzalo Sapisochin, MD, PhD, MSc, Abdominal Transplant & HPB Surgical Oncology, Ajmera Transplant Center, Division of General Surgery, Toronto General Hospital, University of Toronto, 585 University Ave, 11PMB184, Toronto, M5G 2N2, ON, Canada (gonzalo.sapisochin@uhn.ca).

Author Contributions: Drs Hernandez-Alejandro and Ruffolo had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Hernandez-Alejandro, Ruffolo, Sasaki, Tomiyama, Dokus, McGilvray, Ghanekar, Gallinger, Burkes, Hashimoto, Fujiki, Quintini, Menon, Aucejo, Sapisochin.

Acquisition, analysis, or interpretation of data: Hernandez-Alejandro, Ruffolo, Sasaki, Tomiyama, Orloff, Pineda-Solis, Nair, Errigo, Dokus, Cattral, Selzner, Claasen, Fujiki, Estfan, Kwon, Sapisochin.

Drafting of the manuscript: Hernandez-Alejandro, Ruffolo, Sasaki, Errigo, Cattral, Claasen, Menon.

Critical revision of the manuscript for important intellectual content: Hernandez-Alejandro, Ruffolo, Sasaki, Tomiyama, Orloff, Pineda-Solis, Nair, Dokus, Cattral, McGilvray, Ghanekar, Gallinger, Selzner, Claasen, Burkes, Hashimoto, Fujiki, Quintini, Estfan, Kwon, Aucejo, Sapisochin.

Statistical analysis: Hernandez-Alejandro, Ruffolo, Fujiki, Quintini.

Administrative, technical, or material support: Hernandez-Alejandro, Ruffolo, Orloff, Nair, Errigo, Dokus, McGilvray, Ghanekar, Selzner, Claasen, Burkes.

Supervision: Hernandez-Alejandro, Ruffolo, Sasaki, Tomiyama, Pineda-Solis, Gallinger, Menon, Aucejo, Sapisochin.

Conflict of Interest Disclosures: Dr Kwon reported receiving grants from Medtronic, Integra LifeSciences, Olympus, Fujifilm, and Ethicon outside the submitted work. Dr Sapisochin reported receiving grants from Roche and Bayer and personal fees from Integra, Roche, AstraZeneca, and Novartis outside the submitted work. No other disclosures were reported.