Multidisciplinary Management of Recurrent Hepatocellular Carcinoma Following Liver Transplantation

Abstract

Introduction Tumor recurrence remains a main limitation to the long-term survival of patients following liver transplantation for hepatocellular carcinoma (HCC). While the majority of patients recur in the first two years after transplantation, late recurrence is not infrequent. Discussion Most common sites of recurrence in order of decreasing frequency are liver graft, lung, bone, abdominal lymph nodes, adrenal glands and peritoneum. Reported five-year survival after surgical resection ranges from 27-88%. Few patients, however, are candidates for surgical resection. Other therapeutic options for recurrent HCC include systemic therapy, intra-arterial therapy, or radiation therapy. Although systemic molecular targeted therapy is generally tolerated with very few interactions with immunosuppressive medications, there is only modest success regarding prolongation of survival. Utilization of radiation therapy for extrahepatic recurrences similarly has minimal impact on overall survival, but may effectively in palliate symptoms. While late recurrence is associated with a more favorable prognosis than early recurrences, prognosis is still poor. Conclusion Late recurrence of HCC following transplantation should be borne in mind even after many years from transplant. Surgical salvage, when feasible, remains a viable treatment option in select patients with a chance for long-term survival. A multi-disciplinary approach is critical as different therapeutic modalities have a role in treating recurrent HCC following transplant.

Late Extrahepatic Recurrence of Hepatocellular Carcinoma after Liver Transplantation: A Rare Case Report and Literature Review

“…In addition, only two previous case reports describe recurrences occurring over 10 years after LT [7,8] . Beyond the Milan criteria, other HCC factors associated with late recurrence are small tumor size, absence of microvascular invasion and well to moderate HCC differentiation: all these features are present in our case [4] . Furthermore, our patient obtained a SVR after treatment for HCV recurrence in the graft, turning off chronic hepatitis with advanced fibrosis before the development of cirrhosis, both conditions considered risk factors for intrahepatic HCC recurrence [9] .…”

“…Since the adoption of Milan criteria in 1996, liver transplantation for HCC has been associated with an excellent long-term outcome, with a 5-and 10-year survival of 73% and 70%, respectively [4] . Nevertheless, tumor recurrence occurs in 3.5% to 21% of recipients, despite careful pre-transplant staging and patient selection, and represents one of the major drawbacks for long-term survival, with a median survival period of 5 months by the onset of the recurrence [5] .…”

“…Nevertheless, tumor recurrence occurs in 3.5% to 21% of recipients, despite careful pre-transplant staging and patient selection, and represents one of the major drawbacks for long-term survival, with a median survival period of 5 months by the onset of the recurrence [5] . More than eighty percent of recurrences occur within the first 2 years of LT, with a median time of 8 to 14 months [6] ; they can involve not only the graft, but also extrahepatic organs such as lungs, bone, lymph nodes, adrenal glands and peritoneum, in descending order of frequency [4] . Very late recurrences (i.e.…”

“…Several studies have shown that an aggressive screening protocol after LT allows early detection of localized and resectable HCC recurrence, which could be susceptible to a possibly curative surgical treatment [14,15] . Indeed, multivariate analysis revealed that surgical treatment is independently associated with prolonged survival (HR 2.5, p = 0.016) [4] . However these findings were observed in transplant recipients with early recurrence of HCC, which mainly shows intrahepatic localization, but not in patients with late recurrence with extrahepatic spread, less liable to a therapeutic intervention [12] .…”

“…According to Milan criteria in the selection of "optimal candidates" to LT, the recurrence rate of HCC is reported below 15% [2] . Most recurrences appear within 2 years after LT; before transplant, the tumor factors associated with higher likelihood of recurrence are diameter > 5 cm, poor differentiation and vascular invasion [3,4] . The majority of recurrences occur within the donor liver, even if an extra-hepatic site may be involved in 10-43% of patients [4] .…”