Down-staged Liver Cancer Associated With Good Post-transplant Outcomes

For patients with liver cancer (also known as hepatocellular carcinoma), transplantation has been restricted to those who fit the Milan criteria. Their tumors must involve one lesion less than or equal to five centimeters in diameter, or two to three lesions each less than or equal to three centimeters. However, studies have suggested that patients with slightly larger lesions may also do well with a transplant.

Rather than expand the Milan criteria, researchers have suggested down-staging hepatocellular carcinoma to select for tumors with more favorable biology that will respond to treatment and do well following liver transplantation. The impact of successful down-staging on post-transplant outcomes was heretofore unknown.

Researchers, led by Francis Yao of the University of California at San Francisco, conducted a prospective study of down-staging protocol and report intention-to-treat survival, dropout and post-transplant tumor recurrence, along with factors that may influence response to down-staging treatment.

Between June 2002 and January 2007, the researchers enrolled 61 liver cancer patients whose tumor stage exceeded the Milan criteria. Fifty-five of these patients received a combination of laparoscopic radiofrequency ablation (RFA) and transarterial chemoembolization (TACE). The remaining 6 patients underwent resection as the down-staging procedure.

Down-staging was successful in 43 of the 61 patients (70.5 percent), and 35 of those received a liver transplant after a median of 8.2 months. While two of the transplant recipients died (one from graft problems and the other from recurrent hepatitis C infection), the remaining 33 were alive and free of liver cancer recurrence after a median follow-up of 25 months.

In the patients for whom down-staging was unsuccessful, 15 had tumor progression, while 3 died (two related to the down-staging, the other not.)

Comparing the clinical characteristics of the 35 patients who received a liver transplant to the 18 patients with treatment failure, only median alpha fetoprotein (AFP) level was significantly different. Treatment failure was the eventual outcome in seven of the eight patients with pre-treatment AFP > 1000 ng/mL. "High AFP may be a marker for vascular invasion or extra-hepatic disease that escapes detection by conventional imaging techniques," the authors suggest.

The authors note the heterogeneity of they loco-regional therapy may be a weakness of their study, and that the optimal treatment should be determined on a case-by-case basis. They also point out that 25 months of post-transplant follow-up may be too short to fully determine the risk of liver cancer recurrence.

Still, they conclude, "our results suggest that tumor down-staging to meet conventional criteria for orthotopic liver transplantation (OLT) among carefully selected patients is associated with excellent post-transplant outcome. Down-staging put selection pressure against aggressive tumors that are likely to progress despite treatment, whereas tumors with more favorable histology are more likely to respond to treatment and do well after OLT."

They call for further studies to refine down-staging treatment strategies to improve the intention-to-treat outcome.