Recurrent Hepatocellular Carcinoma After Living Donor Liver Transplantation: A Preventable Problem or an Acceptable Risk?

Hepatocellular carcinoma (HCC) remains one of the most important surgical diseases worldwide, as it is the 3rd deadliest malignancy accounting for more than 700,000 deaths worldwide. Estimated new cases number close to 800,000 cases annually, and in many parts of the world HCC incidence is increasing faster than any other cancer. Treatment strategies for HCC are also evolving quickly as new local and systemic therapeutic innovations develop. The heterogeneous treatment options can be confusing to patients and providers alike; often such protean approaches to a single disease suggest we have not arrived yet upon the most favorable strategy. For many patients, liver transplantation appears to represent that optimal approach—allowing definitive resection of the malignancy while treating underlying chronic liver disease. However, the application of liver transplantation to patients with HCC has been limited by donor organ scarcity, the tremendous resources required, and the significant risks inherent to the procedure. In this edition of the journal, Taketomi and colleagues report on the downstream consequences and oncologic principles involved with extending criteria for transplantation of HCC using living liver donation. Living donor liver transplantation (LDLT) has several notable advantages in its application to HCC including: avoidance of prolonged waiting times for deceased donor organs, allowing elective timing of transplantation to correlate with pretransplant neoadjuvant and downstaging strategies, preventing patients with advanced malignancies from competing with patients with benign causes of liver failure awaiting transplant, and providing organ replacement therapy in parts of the world where brain death and deceased donation are less commonly accepted. As LDLT is offered to patients with more advanced HCC, careful attention to posttransplant outcomes is required, including the appropriate management of recurrent disease. The group from Kyushu University Hospital describes their experience with a cohort of 101 adult patients treated for HCC with LDLT, focusing on the management of 17 patients who developed recurrent HCC after transplant. All but 1 of the patients with recurrent disease were transplanted for tumors beyond Milan criteria, which have become broadly accepted as the appropriate criteria for recipient selection with relatively few exceptions. The group described a liberal approach to patient selection, with extrahepatic disease and gross vascular invasion stated as the only hard contraindications to transplantation. Tumor burden (size or number of tumors) was not considered as criteria for selection, except to stratify patients for adjuvant systemic chemotherapy. The authors report the use of a rather robust immunosuppression regimen, using 3 drugs and induction with an IL-2 receptor antagonist. The reported survival in patients without tumor recurrence is outstanding, and a testament to the Kyushu group’s technical prowess with LDLT. The authors took an aggressive approach to recurrent HCC posttransplant. Multimodality therapy including surgical resection, radiofrequency ablation, radiation therapy, and systemic chemotherapy was fastidiously employed to attack areas of recurrent disease. Despite relatively early recurrences (mean time from transplant 12.9 months, earliest in the 2nd month), 9 of the 17 recurrent patients underwent 1 or more surgical resections, and these select individuals were able to achieve overall patient survival that was similar to patients without tumor recurrence, though many of the patients appear to have residual disease. Patients who were not eligible for surgical resection of recurrent disease had uniformly poor outcomes, with all but 1 dead of recurrent disease by 26 months post-transplant. Systemic chemotherapy alone, which did not include sorafenib, did not appear to have an impact on either the development of recurrent disease or on overall survival. Society of Surgical Oncology 2010