Disclosures: Dueland reports no relevant financial disclosures. See the abstract for all researchers’ relevant financial disclosures. Fong reports consultant roles with Johnson & Johnson and Medtronic and royalties from Imugene and Merck. Quillin and Shah reports no relevant financial disclosures.
April 08, 2021
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Liver transplantation may benefit certain patients with colorectal cancer liver metastases

Disclosures: Dueland reports no relevant financial disclosures. See the abstract for all researchers’ relevant financial disclosures. Fong reports consultant roles with Johnson & Johnson and Medtronic and royalties from Imugene and Merck. Quillin and Shah reports no relevant financial disclosures.
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Liver transplantation may extend OS compared with portal vein embolization and liver resection for selected patients with advanced colorectal cancer liver metastases and a left-sided primary tumor, according to a study in JAMA Surgery.

A right-sided primary tumor, however, is distinct negative prognostic factor, researchers concluded.

Liver transplantation may extend OS compared with portal vein embolization and liver resection for selected patients with advanced colorectal cancer liver metastases and a left-sided primary tumor.
Data were derived from Dueland S, et al. JAMA Surg. 2021;doi:10.1001/jamasurg.2021.0267.

“Liver transplantation is probably the best medical treatment option for highly selected [patients with colorectal cancer] with liver-only metastases and high tumor load,” Svein Dueland, MD, PhD, of the clinical cancer research unit in the department of oncology at Oslo University Hospital in Norway, told Healio. “Increased liver tumor load increases the risk for relapse after liver resection. The reason for this observation is likely that the liver contains undetectable small liver metastases in addition to metastatic sites determined by MRI/CT scans at time of liver resection. Liver transplantation results in a new liver without occult metastases, eliminating missed tumor cells left in place during a liver resection procedure.”

Dueland and colleagues compared OS among patients with colorectal cancer and high liver metastasis tumor load who underwent liver transplant vs. portal vein embolization and liver resection.

The analysis included 50 patients with colorectal cancer and liver metastases previously enrolled in liver transplant studies between November 2006 and August 2019 at Oslo University Hospital. Of them, 29 had high tumor load, defined as nine or more metastatic tumors or a diameter of at least 5.5 cm for the largest liver lesion. Twenty-one of these patients (median age, 53 years; men, n = 13) had a left-sided primary tumor, whereas eight (median age, 49.6 years; men, n = 8) had ascending colon primary tumor.

Researchers compared the liver transplant recipients with a retrospective group of 53 matched patients (median age, 61.8 years; men, n = 36) from the hospital’s portal vein embolization (PVE) database who underwent PVE and liver resection between March 2006 and November 2015.

Dueland and colleagues used the Kaplan-Meier method to estimate survival. Results showed 5-year OS rates of 44.6% among 38 patients who underwent liver resection after PVE.

Patients with low tumor load had 5-year OS rates of 72.4% with liver transplant and 69.3% with liver resection after PVE.

Among patients with high tumor load, researchers observed 5-year OS rates of 33.4% with liver transplant and 6.7% with PVE. Among patients with high tumor load and a left-sided primary tumor, 5-year OS rates were 45.3% for those receiving a liver transplant (vs. 0% with a right-sided tumor) and 12.5% for those treated with PVE and liver resection.

Svein Dueland, MD, PhD
Svein Dueland

“We had previously published that [patients with colorectal cancer] with high tumor load had good overall survival compared with previous published data from patients with less tumor load receiving liver resection, so this confirmed our hypothesis suggesting liver transplantation is probably the best treatment option for these patients if donor grafts are available,” Dueland said.

However, Dueland and colleagues wrote that the “highly controversial” topic could only be addressed further through trials adjusting for the selection bias in their study.

“Liver transplantation for colorectal cancer liver metastases has for many years been considered a contraindication for liver transplantation at most transplant centers due to the high relapse rate after liver transplantation,” Dueland told Healio. “We have, in several publications, shown [patients with colorectal cancer] receiving a liver transplant and having a relapse have long overall survival from time of relapse. Many of the relapses may be resected and the patients obtain a status of no evidence of disease.

“Furthermore, another problem is the lack of donor organ for liver transplantation in general,” Dueland said. “Adding a new indication for liver transplant obviously will not make this situation any better.”

Yuman Fong, MD, chair and professor in the department of surgery and director in the Center for International Medicine and the Center for Surgical Innovation at City of Hope Medical Center, also acknowledged cadaveric livers for transplant remain a finite resource, noting that more than 1,000 patients die yearly on the waiting list for a transplant.

“Patient selection is still key,” Fong wrote in an editorial accompanying the study. “For disease-free patients who are experiencing portal hypertension and liver failure from natural causes or previous systemic and/or regional chemotherapy, a transplant should be considered an option. Those with active liver cancer, a long disease course, good response to chemotherapy and no extrahepatic disease would represent a perfect group for trials or registries.”

Dueland and colleagues laid the groundwork for others to follow by taking a concept from experimental to potential standard of care, but a randomized trials of liver transplant vs. other modalities remain necessary, according to a separate editorial by Ralph C. Quillin III, MD, and Shimul A. Shah, MD, MHCM, of the solid organ transplantation section in the department of surgery at University of Cincinnati College of Medicine.

“A multicenter consortium should be established to monitor and track indications and outcomes following liver transplant,” Quillin and Shaw wrote. “If done in a coordinated and systematic manner, standards of care could be developed that may pave the wave for liver transplant as an option for [colorectal liver metastases], just like we have for hepatocellular carcinoma, unresectable hilar cholangiocarcinoma and metastatic neuroendocrine tumor.”

References:

Dueland S, et al. JAMA Surg. 2021;doi:10.1001/jamasurg.2021.0267.
Fong Y. JAMA Surg. 2021;doi:10.1001/jamasurg.2021.0268
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Quillin RC and Shah, SA. JAMA Surg, 2021; doi:10.1001/jamasurg.2021.0269
.

For more information:

Svein Dueland, MD, PhD, can be reached at Section for Transplantation Surgery, Department of Transplantation Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, N-0424, Oslo, Norway; email: svedue@ous-hf.no.