Increased overall survival compared with portal vein embolization, liver resection

In a highly select group of patients with colorectal cancer and nonresectable liver metastases, high liver tumor load, and left-sided primary tumors, liver transplant brought about significantly higher overall survival (OS) rates compared with portal vein embolization (PVE) and liver resection. Thus, liver transplant may be a viable treatment option in future prospective studies of select patients with colorectal liver metastasis, researchers reported.

Although liver resection is the standard of care in patients with colorectal cancer and liver metastasis, few patients qualify as candidates, according to researchers led by Svein Dueland, MD, PhD, of Oslo University Hospital, Norway, who had previously demonstrated significant differences in OS after liver transplant in patients with primary tumors located in the ascending colon compared with those with primary tumors in the rest of the colon or rectum (left-sided tumors). They published their findings in JAMA Surgery.

They undertook this current comparative effectiveness study to compare OS in patients with colorectal cancer and a high liver metastasis tumor load who underwent liver transplant or PVE and liver resection. For comparison, they enrolled 50 patients with colorectal cancer liver metastases (CCLM) who had been enrolled in liver transplant studies at Oslo University Hospital, Norway, and a retrospective cohort of 53 patients (median age: 61.8 years; 68% men) from the hospital’s PVE database who underwent PVE and liver resection.

High tumor load was defined as ≥9 or more metastatic tumors or a largest liver lesion of ≥5.5 cm. Patients in both the liver transplant and PVE groups were classified according to their tumor load, and those with low tumor loads had significantly better OS compared with those with high tumor loads.

The five-year OS in patients with low tumor load undergoing liver transplant was 72.4%, compared with 33.4% in the 29 patients with high tumor load who underwent liver transplant (median OS: 40.5 months), and compared with 53.1% in low-tumor-load patients undergoing PVE (P=0.08).

In patients with high tumor load, OS was significantly increased (P=0.007) in patients undergoing liver transplant compared with PVE, with a median OS of 40.5 versus 19.2 months, respectively.

Patients with high tumor load and left-sided primary tumors had a 5-year OS of 45.3% after liver transplant, compared with 12.5% in those with high tumor load and left-sided primary tumors who underwent PVE and liver resection. The difference between the liver transplant subgroups with low tumor load and high tumor load was significant (P=0.002).

Location of the primary tumor also had a significant impact on results. In patients with high tumor load, and primary left-sided tumors undergoing liver transplant, median OS was 59.9 months, and 5-year overall survival, 45.3% compared with a median OS of 12.2 and a 5-year OS of 0% in patients with high tumor load undergoing liver transplant with the primary tumor located in the ascending colon.

“Liver transplant among patients with [colorectal cancer liver metastasis] CRLM should still be considered a work in progress, and patients offered LT should therefore be included in prospective trials,” concluded Dueland and colleagues.

Their findings “suggest a possibility of an expanded patient population to seek out for liver transplant,” Ralph C. Quillin III, MD, and Shimul A. Shah, MD, both of the University of Cincinnati College of Medicine, Ohio, wrote in an accompanying editorial. They added that: “While this study was retrospective and not an intention-to-treat direct comparison, Dueland and colleagues should be commended for a very aggressive surgical approach to a heavy tumor burden of CRLM, which many would deem unresectable and palliative from the start.”

The future implications for research—and for patients with colorectal cancer with liver metastases—are hopeful, added Quillin and Shah.

“Dueland et al have laid the groundwork for the world to follow and took a concept from being experimental to possibly standard of care: liver transplant for CRLM with heavy tumor burden. What is lacking from this current work and others is a head-to-head randomized clinical trial of liver transplant to other modalities (chemotherapy, hepatic artery infusion, PVE/resection, etc.). While the inherent limitations of liver transplant (low recipient Model for End-stage Liver Disease scores + deceased donor organ scarcity = limited access to transplant) may make such a trial impossible to conduct, opportunities exist for the cancer community to increase our understanding of this indication for liver transplant in a systematic manner,” they concluded. In a second accompanying editorial, Yuman Fong, MD, of the City of Hope Medical Center, Duarte, California, concluded that results from Dueland et al shine new light on the prospect of liver transplant as a possible treatment for patients with colorectal liver metastases.

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Since the beginning of the use of transplantation, much has changed, Fong wrote, with improved staging, the advent of fluorine 18-labeled fludeoxyglucose-PET scanning for detection of extrahepatic disease, and more effective chemotherapeutic options for colorectal cancer.

What has not changed, however, is the importance of patient selection.

“Patient selection is still key. 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,” Fong wrote.

Limitations of the study include significant differences between the liver transplant and PVE patients including the use of FDG-PET-CT that was required in the liver transplant patients but not the PVE and heavy pretreatment in the liver transplant group at the time of transplant (81% received two or more lines of chemotherapy).

  1. Liver transplant may be a viable treatment option to explore in future prospective studies for select patients with colorectal liver metastasis.

  2. Overall survival among patients with left-sided primary tumor and liver grafts exceeded overall survival among those treated with portal vein embolization and liver resection.

Liz Meszaros, Deputy Managing Editor, BreakingMED™

Eastern Norway Regional Health Authority.

Dueland has declared no conflicts of interest.

Quillin and Shah declared no conflicts of interest.

Cat ID: 23

Topic ID: 78,23,636,730,16,473,23,192,925,159,312