Treatment Option Overview
The decision as to which surgical approach to use depends on many factors including the following:
- PRETEXT stage.
- Size of the primary tumor.
- Presence of multifocal hepatic disease.
- Vascular involvement.
- AFP levels.
- Whether preoperative chemotherapy may convert an unresectable tumor into a potentially resectable tumor.
- Whether hepatic disease meets surgical and histopathologic criteria for orthotopic liver transplantation.
In North American clinical trials, the Children's Oncology Group (COG) has recommended that surgery be performed initially if a complete resection can be accomplished (see the Postsurgical Staging for Childhood Liver Cancer section for more information). In European clinical trials, using the Presurgical Staging system (see Presurgical Staging for Hepatoblastoma and Hepatocellular Carcinoma section for more information), only patients with PRETEXT stage 1 receive resection surgery and all other patients are biopsied. COG is investigating the use of PRETEXT stage at diagnosis and after chemotherapy to determine the optimal surgical approach and its timing (COG-AHEP0731).
It is difficult to compare the North American and European approaches. However, somewhat comparable results for children with PRETEXT stage 1 and 2 tumors were obtained in two international studies in which children with stage 2 disease were treated with delayed surgery (chemotherapy with doxorubicin/cisplatin or cisplatin alone prior to attempted surgical resection of the primary liver tumor). Patients with PRETEXT stage 1 tumors were treated with initial surgery (chemotherapy was given following complete resection).[11,12] Patients with PRETEXT stage 3 tumors were treated with neoadjuvant chemotherapy (four cycles of cisplatin/doxorubicin or cisplatin/vincristine/fluorouracil) with reassessment of resectability and resection if possible, followed by two more cycles of chemotherapy. The overall survival (OS) was 75% at 5 years. The 5-year survival of PRETEXT stage 1 and 2 patients is 90% to 100% on the European studies and seems to be similar to that of children treated on North American studies where surgery was performed before chemotherapy. In comparison, a survey of children with liver tumors who were treated prior to the consistent use of combination chemotherapy found that 45 of 78 patients (57%) with hepatoblastoma who had complete excision of the tumor survived while no children with positive margins or gross disease following resection survived.
Orthotopic liver transplantation
Liver transplantation has recently been associated with significant success in the treatment of children with unresectable hepatic tumors.[13,14,15][Level of evidence: 3iiA] A review of the world experience has documented a posttransplant survival rate of 70% to 80% for children with hepatoblastomas.[10,16,17] Intravenous invasion, positive lymph nodes, and contiguous spread did not have a significant adverse effect on outcome. It has been suggested that adjuvant chemotherapy following transplant may decrease the risk of tumor recurrence.
There are discrepant results on the outcomes for patients with lung metastases at diagnosis who undergo orthotopic liver transplantation following complete resolution of lung disease in response to pretransplant chemotherapy. Some studies have reported favorable outcomes for this group of patients, while others have noted high rates of hepatoblastoma recurrence.[17,19] All of these studies are limited by small patient numbers; further study is needed to better define outcomes for this subset of patients.