Recent Advances in the Treatment of Hepatocellular Carcinoma

Amit G. Singal; Jorge A. Marrero


Curr Opin Gastroenterol. 2010;26(3):189-195. 

In This Article

Liver Transplantation

Liver transplantation is a unique treatment for HCC in that it not only removes the tumor but also corrects the underlying liver disease, thus minimizing the risk of new tumors in the future. Patients receive priority listing for transplantation in the United States if they meet 'Milan criteria', that is, one tumor less than 5 cm or three tumors less than 3 cm each without vascular invasion or extrahepatic spread.[20] When these criteria are applied, recurrence rates are typically less than 15% and 5-year survival rates approach 68%.[21] In a recent analysis of liver transplant candidates with HCC in the UNOS database from 1998 to 2006, overall 5-year survival rates approached 62% after liver transplantation (Fig. 2). Independent predictors of survival included age less than 55 years (hazard ratio 0.76), Child–Pugh class (1.40 for Child class B and 2.20 for Child class C), undergoing transplant (hazard ratio 0.23), and having a tumor within Milan criteria (hazard ratio 0.49).[22••]

Figure 2.

Intention-to-treat survival of patients listed for hepatocellular carcinoma in the UNOS database from 1998 to 2006
Reproduced from [22••].

Some have proposed expanding selection criteria to include patients with a single lesion smaller than 6.5 cm or up to three lesions, each less than 4.5 cm with a maximum tumor burden of 8.0 cm, known as the University of California San Francisco (UCSF) criteria.[23] The benefit to patients who meet UCSF criteria must be weighed against the harm from delaying transplantation in other patients on the waiting list (Fig. 3). The harms of expanding selection criteria typically outweigh the benefits when 5-year posttransplant survival rates fall below 61%.[24••] Although promising results have been reported from single-center cohort studies, patients exceeding Milan criteria only had a 5-year posttransplant survival of 38% in the UNOS database.[22••] Further data validating the UCSF criteria are necessary before expanded selection criteria are adopted as standard protocol.

Figure 3.

Sensitivity analysis of the benefits and harms of expanding Milan criteria
Reproduced from [24••].

An alternative approach to expanding tumor size limits is downstaging tumors to Milan criteria by chemoembolization, percutaneous ablation, or resection. Theoretically, this process selects tumors with more favorable biology that responds to downstaging treatments and would likely also do well after transplantation.[25] In a prospective study in 61 patients, successful downstaging was observed in 43 (70%) patients.[26] Among the 35 patients who underwent transplant, 33 remained alive without tumor recurrence after a median follow-up of 25 months. The 4-year intention-to-treat survival rate of the entire cohort was 69%, with a 4-year survival rate of 92% in the 35 patients who underwent transplant. Although these results are promising, confirmation in larger cohorts is still needed.


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