Transplant May Be Reasonable for Certain CRC Patients With Liver Mets

For a select group of patients with colorectal cancer and unresectable liver metastases, liver transplant may be a reasonable option, according to results from a prospective, nonrandomized controlled cohort study.

Overall, among 61 patients who underwent liver transplant, the median disease-free survival (DFS) was 11.8 months (95% CI 9.3-14.2), with a 5-year DFS rate of 18.3%, and the median overall survival (OS) was 60.3 months (95% CI 44.3-76.4), with a 5-year OS rate of 50.4%, reported Svein Dueland, MD, PhD, of Oslo University Hospital in Norway, and colleagues.

Seventy-eight percent of patients had a relapse after liver transplant, with a median time to relapse of 9.0 months. Median survival from time of relapse was 37.1 months (95% CI 4.6-69.5), with a 5-year survival after relapse of 34.8%, they noted in JAMA Surgery.

However, “based on various clinical predictive factors, a 10-year overall survival rate of 80% or more may be achieved in selected cases,” Dueland and team wrote.

For example, they found that an Oslo score of 0 yielded a median OS of 151.6 months, with 5- and 10-year OS rates of 88.9%, while a Fong Clinical Risk Score of 1 yielded a median OS of 164.9 months, with 5- and 10-year OS rates of 100% and 80%, respectively.

The Oslo score ranges from 0 to 4 based on the following factors: progressive disease while receiving chemotherapy at time of organ transplant, plasma carcinoembryonic antigen (CEA) level >80 μg/L, size of largest liver lesion ≥5.5 cm, and time for resection of the primary tumor to liver transplant <2 years. The Fong Clinical Risk Score ranges from 0 to 5, with 1 point for <12 months from diagnosis of the primary tumor to liver metastases, size of largest lesion >5 cm, more than one lesion, plasma CEA level >200 μg/L, and a positive lymph node in the primary tumor.

In this study, negative predictive factors for OS included:

• Largest tumor size greater than 5.5 cm (median OS of 25.3 months)
• Progressive disease while receiving chemotherapy (median OS of 39.8 months)
• Plasma CEA values greater than 80 μg/L (median OS of 26.6 months)
• Liver metabolic tumor volume greater than 70 cm³ on PET (median OS of 26.6 months)
• Primary tumor in the ascending colon (median OS of 17.9 months)
• Tumor burden score of 9 or higher (median OS of 23.3 months)
• Nine or more liver lesions (median OS of 42.5 months)

“The most compelling argument in favor of liver transplant lies in the likely curative potential evidenced by the 13 disease-free patients and ongoing development of optimal selection criteria,” wrote Ryan J. Ellis, MD, and Michael I. D’Angelica, MD, both of Memorial Sloan Kettering Cancer Center in New York City, in a commentary accompanying the study.

“In attempting to optimize selection criteria, it is equally important to identify those patients who can be removed from the potential transplant algorithm early and transition to other therapies,” they added.

“It seems likely that there is a small group of patients with unresectable colorectal liver metastases who should be considered for transplant, and long-term survival and possibly cure are achievable in these patients with appropriate selection,” they concluded.

They noted that while previous experience with liver transplant for patients with unresectable colorectal liver metastases “was met with dismal results” and the approach was largely discontinued, Dueland and colleagues have “truly revitalized this concept.”

In explaining their rationale, Dueland and team noted that while liver resection is considered the only curative treatment for patients with colorectal cancer and liver metastases, only about 20% of these patients are candidates for surgery, with 5-year OS rates of 30% to 50% after resection. Furthermore, for most patients, the only treatment option is palliative chemotherapy, with a reported median OS of 24 to 30 months and a 5-year OS rate of 10%.

On the other hand, liver transplant is standard of care for patients with end-stage liver failure, for selected patients with hepatocellular carcinoma within the Milan criteria, and selected patients with low-grade neuroendocrine tumors, with 5-year OS rates ranging from 63% to 75%.

The authors said their study results “suggest that selected patients with liver-only metastases and favorable pretransplant prognostic scoring had long-term survival comparable with conventional indications for liver transplant, thus providing a potential curative treatment option in patients otherwise offered only palliative care.”

For this study, Dueland and colleagues included 61 patients (median age 57.8 years, 57.4% men) who underwent liver transplant at Oslo University Hospital from November 2006 to November 2020.

Post-transplant observation time ranged from 16 to 165 months, and no patients were lost to follow-up.

The authors acknowledged that a major obstacle to liver transplant in these patients was the scarcity of donor grafts, but suggested that this could be overcome by using extended-criteria donor grafts and the RAPID [Resection and Partial Liver Segment 2/3 Transplantation With Delayed Total Hepatectomy] technique with deceased or living donors.