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Treatment options for hepatoblastoma with metastases at diagnosis
Source: Childhood Liver Cancer Treatment (PDQ®)–Health Professional Version, National Cancer Institute.
Source updated: January 6, 2025 · Captured 2026-09-09.
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Context: Hepatoblastoma / Treatment of Hepatoblastoma
The outcomes of patients with metastatic hepatoblastoma at diagnosis are poor, but long-term survival and cure are possible.[51,66,67] Survival rates at 3 to 5 years range from 20% to 79%.[55,57,74,117] To date, the best outcomes for children with metastatic hepatoblastoma resulted from treatment with dose-dense cisplatin and doxorubicin, although significant toxicity was also noted (SIOPEL-4 [NCT00077389] trial).[74][Level of evidence B4]
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Treatment options for hepatoblastoma with metastases at diagnosis include the following:
Chemotherapy followed by reassessment of surgical resectability.
Chemotherapy followed by reassessment of surgical resectability.
If the primary tumor and extrahepatic disease (usually pulmonary nodules) are resectable after chemotherapy, surgical resection is followed by additional chemotherapy.
Chemotherapy followed by reassessment of surgical resectability.
If extrahepatic metastatic disease is in complete remission after chemotherapy and/or surgical resection of lung nodule but the primary tumor remains unresectable, orthotopic liver transplant is warranted.
If extrahepatic metastatic disease is not resectable or the patient is not a transplant candidate, additional chemotherapy, TACE, TARE, or radiation therapy may be indicated.[106]
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The standard combination chemotherapy regimen in North America is four courses of cisplatin/vincristine/fluorouracil [51] or doxorubicin/cisplatin,[52,54,55] followed by attempted complete tumor resection. If the tumor is completely removed, two postoperative courses of the same chemotherapy are usually given. Study results for different chemotherapy regimens have been reported. For more information, see Table 6.
High-dose chemotherapy with stem cell rescue does not appear to be more effective than standard multiagent chemotherapy.[118]
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Evidence (chemotherapy followed by surgery to treat metastatic disease at diagnosis):
A subset of 39 patients presenting with metastases were enrolled in the SIOPEL-4 (NCT00077389) trial, a multinational feasibility trial of dose-dense cisplatin/doxorubicin chemotherapy and radical surgery for a group of children with high-risk hepatoblastoma. Patients who underwent liver resection or transplant after three cycles of chemotherapy subsequently received two postoperative cycles of carboplatin and doxorubicin. Patients whose tumors were unresectable after three cycles of chemotherapy received two additional cycles of very intensive carboplatin and doxorubicin before surgery.[74][Level of evidence B4]
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A subset of 39 patients presenting with metastases were enrolled in the SIOPEL-4 (NCT00077389) trial, a multinational feasibility trial of dose-dense cisplatin/doxorubicin chemotherapy and radical surgery for a group of children with high-risk hepatoblastoma. Patients who underwent liver resection or transplant after three cycles of chemotherapy subsequently received two postoperative cycles of carboplatin and doxorubicin. Patients whose tumors were unresectable after three cycles of chemotherapy received two additional cycles of very intensive carboplatin and doxorubicin before surgery.[74][Level of evidence B4]
After three cycles of chemotherapy, there was a complete response (only in the metastases) in 20 of 39 patients and a partial response in 18 of 39 patients. Nineteen of the patients who achieved a complete response were alive without disease 3 years after diagnosis.
A subset of 39 patients presenting with metastases were enrolled in the SIOPEL-4 (NCT00077389) trial, a multinational feasibility trial of dose-dense cisplatin/doxorubicin chemotherapy and radical surgery for a group of children with high-risk hepatoblastoma. Patients who underwent liver resection or transplant after three cycles of chemotherapy subsequently received two postoperative cycles of carboplatin and doxorubicin. Patients whose tumors were unresectable after three cycles of chemotherapy received two additional cycles of very intensive carboplatin and doxorubicin before surgery.[74][Level of evidence B4]
Of the patients who achieved a partial response, seven patients underwent metastasectomy near the time of resection or liver transplant, with an OS rate of 100%. An additional seven patients with residual small pulmonary nodules underwent resection without metastasectomy; of those, six patients did well and one patient had a recurrence.
A subset of 39 patients presenting with metastases were enrolled in the SIOPEL-4 (NCT00077389) trial, a multinational feasibility trial of dose-dense cisplatin/doxorubicin chemotherapy and radical surgery for a group of children with high-risk hepatoblastoma. Patients who underwent liver resection or transplant after three cycles of chemotherapy subsequently received two postoperative cycles of carboplatin and doxorubicin. Patients whose tumors were unresectable after three cycles of chemotherapy received two additional cycles of very intensive carboplatin and doxorubicin before surgery.[74][Level of evidence B4]
Two patients with initial metastases eventually experienced a recurrence.
A subset of 39 patients presenting with metastases were enrolled in the SIOPEL-4 (NCT00077389) trial, a multinational feasibility trial of dose-dense cisplatin/doxorubicin chemotherapy and radical surgery for a group of children with high-risk hepatoblastoma. Patients who underwent liver resection or transplant after three cycles of chemotherapy subsequently received two postoperative cycles of carboplatin and doxorubicin. Patients whose tumors were unresectable after three cycles of chemotherapy received two additional cycles of very intensive carboplatin and doxorubicin before surgery.[74][Level of evidence B4]
Liver transplant, rather than resection alone, was needed to treat 7 of the 39 patients who presented with metastases.
A subset of 39 patients presenting with metastases were enrolled in the SIOPEL-4 (NCT00077389) trial, a multinational feasibility trial of dose-dense cisplatin/doxorubicin chemotherapy and radical surgery for a group of children with high-risk hepatoblastoma. Patients who underwent liver resection or transplant after three cycles of chemotherapy subsequently received two postoperative cycles of carboplatin and doxorubicin. Patients whose tumors were unresectable after three cycles of chemotherapy received two additional cycles of very intensive carboplatin and doxorubicin before surgery.[74][Level of evidence B4]
For the subset of 39 patients presenting with metastases, the 3-year DFS rate was 77% (95% CI, 63%–90%), and the OS rate was 79% (95% CI, 66%–92%).
In patients with resected primary tumors, any remaining pulmonary metastases should be surgically removed, if possible.[55] Resection of pulmonary metastases may be facilitated by computed tomography needle localization or preoperative indocyanine green administration with intraoperative fluorescence localization.[119] A review of patients treated on a U.S. intergroup trial suggested that resection of metastasis may be done at the time of resection of the primary tumor.[117][Level of evidence C1]
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If extrahepatic disease is in complete remission after chemotherapy, and the primary tumor remains unresectable, an orthotopic liver transplant may be performed.[52,57,74,110]
The outcome results are discrepant for patients with lung metastases at diagnosis who undergo orthotopic liver transplant after complete resolution of lung disease in response to pretransplant chemotherapy. Some studies have reported favorable outcomes for these patients,[57,74,102,110] while others have noted high rates of hepatoblastoma recurrence.[71,98,101,104] All of these studies are limited by small patient numbers. Additional studies are needed to better define outcomes for this subset of patients. Recent clinical trials have resulted in few pulmonary recurrences in children who presented with metastatic disease and underwent liver transplants.[57,59,74]
If extrahepatic disease is not resectable after chemotherapy or the patient is not a transplant candidate, alternative treatment approaches include the following:
Other chemotherapy agents. Chemotherapy agents such as irinotecan, high-dose cisplatin/etoposide, or continuous-infusion doxorubicin have been used.[120-122]; [123][Level of evidence C1]
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Radiation therapy.[125]
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Studies cited in this source section
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Preserved source evidence · Not medical advice