Living Donor Transplant Promising for CRC With Liver-Only Metastases

Select patients with unresectable colorectal cancer liver metastases (CRLMs) had good survival outcomes following total hepatectomy and living-donor liver transplant (LDLT), a prospective study of 10 patients found.

In the series involving liver-confined metastatic disease in patients with a sustained response to oncologic therapy, Kaplan-Meier estimates of recurrence-free and overall survival at 1.5 years were an “encouraging” 62% and 100%, respectively, reported Gonzalo Sapisochin, MD, PhD, of the University of Toronto, and colleagues.

“This study was the first contemporary experience, to our knowledge, to use LDLT to treat patients with unresectable CRLMs,” they wrote in JAMA Surgery.

The survival results mirror those from a prior series in Oslo, Norway, but which relied on deceased donor organs. While transplant was reported to improve long-term survival versus chemotherapy for patients with CRLMs in the Oslo study, access to deceased-donor allografts is a challenge in most nations, where patients with higher Model for End-Stage Liver Disease (MELD) scores take priority.

“[LDLT] provides an alternative for patients in the U.S. and Canada without further straining the organ-scarce liver waiting list,” noted Sapisochin and colleagues.

“However, LDLT must be used in clinical scenarios in which the potential benefits for the recipient are carefully weighed against the risk of donor morbidity and mortality,” they continued. “Selecting patients with unresectable CRLMs who are most likely to have long-term benefit is critical, thus meeting the standard of double equipoise.”

In the current study, recipients and donors had perioperative morbidity consistent with established standards of Clavien-Dindo complications:

• Recipients: four of the 10 had grade III, three had grade II, and three had none
• Donors: one had grade III, four had grade I, and five had none

In an accompanying editorial, Shimul Shah, MD, MHCM, of the University of Cincinnati College of Medicine in Ohio, and Parsia Vagefi, MD, of the University of Texas Southwestern Medical Center in Dallas, stressed the need for proper patient selection — noting that three of the 10 patients in the study had recurrences within 199 days of transplant (one of whom later died following palliative treatment) — and for optimizing this selection.

“It is imperative to better understand favorable tumor biology that goes beyond a perceived response to systemic and local therapies, because we are missing the mark if favorable tumor biology leads to recurrence within 6 months after transplant,” the duo stated. “We must carefully consider the use of living liver donors for this indication, given not only the current uncertainties in management of CRLM but also the growing number and availability of deceased donors and technologies such as machine perfusion, which will allow the broader sharing of marginal organs.”

Shah and Vagefi also highlighted one limitation of the series, in that the centers involved relied on three different protocols, and the extent of patients’ overall tumor burden was unclear.

For their study, Sapisochin and colleagues evaluated 91 patients at three leading transplant centers in the U.S. and Canada. In all, 12 had a sustained response to oncologic therapy and 10 with liver-confined unresectable CRLMs ultimately underwent total hepatectomy and LDLT from July 2017 to October 2020. Median time from CRLM diagnosis to LDLT was 1.7 years, and the patients were followed for up to 5 years.

“To ensure the highest chance of oncologic success, we selected patients with low Oslo Scores [median 1.5] and Clinical Risk Scores [median 2.5] who demonstrated sustained response to systemic and local therapies, suggestive of favorable tumor biology,” the study authors explained.

Among the 10 donors, seven were men, the median age was 41, and the median length of hospital stay was 6 days. Of the 10 transplant recipients, six were men and the median age was 45.

Four CRLMs patients had undergone a prior liver resection, three underwent hepatic artery infusion chemotherapy (22.5 median cycles), and three had undergone tumor ablation. At LDLT, eight had bilobar disease on pre-operative imaging, while two had “right-sided resections with recurrence in the liver remnant.” Nine had normal liver function, while one had secondary liver dysfunction from chemotherapy. Three patients had background cirrhosis on pathology.

Following transplant, patients received immunosuppressants therapy. Seven recipients experienced postoperative complications: acute rejection, biliary complications, ileus, hepatic artery thrombosis (requiring a de-clotting surgery), and organ space infection.