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Childhood Liver Cancer Treatment (PDQ®)

Health Professional Version
Last Modified: 12/14/2011

Stage Information

Presurgical Staging for Hepatoblastoma and Hepatocellular Carcinoma
        PRETEXT stage 1
        PRETEXT stage 2
        PRETEXT stage 3
        PRETEXT stage 4
        PRETEXT designations
        Hepatoblastoma and hepatocellular carcinoma prognosis by PRETEXT stage
Postsurgical Staging for Childhood Liver Cancer
        Hepatoblastoma prognosis by postsurgical stage
        Hepatocellular carcinoma prognosis by postsurgical stage of disease at diagnosis
Clinical Trials Under Evaluation: COG Hepatoblastoma Risk Groups

There are two standard surgical staging systems for pediatric liver tumors. The Childhood Liver Tumour Strategy Group (SIOPEL) uses a presurgical-based staging system, while the Children's Oncology Group (COG) uses a postsurgical-based staging system. The staging systems support different treatment strategies. The presurgical staging system is used with neoadjuvant chemotherapy followed by definitive surgery (with the exception of Pretreatment Extent of Disease [PRETEXT] stage 1), while the postsurgical staging system has surgery as the initial strategy.

Both systems are used in the United States. In a retrospective comparison of the two staging systems at diagnosis using data from patients entered on a North American randomized trial, both staging systems predicted outcome. The presurgical PRETEXT staging system may add prognostic information for patients staged postsurgically at stage 3.[1] The COG is investigating the use of PRETEXT stage before and after chemotherapy to determine the optimal surgical approach (COG-AHEP0731 1).

Presurgical Staging for Hepatoblastoma and Hepatocellular Carcinoma

The PRETEXT staging system for hepatoblastoma categorizes the primary tumor based on extent of liver involvement at diagnosis. The staging system was devised for use in an international hepatoblastoma treatment program in which only children with PRETEXT stage 1 hepatoblastoma undergo initial resection of tumor. All others are treated with chemotherapy prior to attempted resection of the primary tumor. The liver tumors are staged by interpretation of computerized tomography or ultrasound with or without additional imaging by magnetic resonance. The presence or absence of metastases is noted in addition to the PRETEXT stage, but does not alter the PRETEXT stage. Tumor involvement of the vena cava, hepatic veins, and portal vein, and extrahepatic extension are also noted.

The imaged liver is divided into four quadrants and involvement of each quadrant with tumor is determined. Stage increases and prognosis decreases as the number of quadrants radiologically involved with tumor increases from one to four.[2,3] Experienced radiologist review is important because it may be difficult to discriminate between real invasion beyond the anatomic border of a given sector and displacement of the anatomic border.[3,4]

PRETEXT stage 1

Enlarge
Liver PRETEXT Stage 1; drawing shows two livers. Dotted lines divide each liver into four vertical segments of about the same size. In the first liver, cancer is shown in the segment on the far left. In the second liver, cancer is shown in the segment on the far right.


  • Tumor involves only one quadrant; three adjoining liver quadrants are free of tumor.
PRETEXT stage 2

Enlarge
Liver PRETEXT Stage 2; drawing shows five livers. Dotted lines divide each liver into four vertical segments that are about the same size. In the first liver, cancer is shown in the two segments on the left. In the second liver, cancer is shown in the two segments on the right. In the third liver, cancer is shown in the far left and far right segments. In the fourth liver, cancer is shown in the second segment from the left. In the fifth liver, cancer is shown in the second segment from the right.


  • Tumor involves one or two quadrants; two adjoining quadrants are free of tumor.
PRETEXT stage 3

Enlarge
Liver PRETEXT Stage 3; drawing shows seven livers. Dotted lines divide each liver into four vertical segments that are about the same size. In the first liver, cancer is shown in three segments on the left. In the second liver, cancer is shown in the two segments on the left and the segment on the far right. In the third liver, cancer is shown in the segment on the far left and the two segments on the right. In the fourth liver, cancer is shown in three segments on the right. In the fifth liver, cancer is shown in the two middle segments. In the sixth liver, cancer is shown in the segment on the far left and the second segment from the right. In the seventh liver, cancer is shown in the segment on the far right and the second segment from the left.


  • Tumor involves three quadrants and one quadrant is free of tumor or tumor involves two quadrants and two nonadjoining quadrants are free of tumor.
PRETEXT stage 4

Enlarge
Liver PRETEXT Stage 4; drawing shows two livers. Dotted lines divide each liver into four vertical segments that are about the same size. In the first liver, cancer is shown across all four segments. In the second liver cancer is shown in the two segments on the left and spots of cancer are shown in the two segments on the right.


  • Tumor involves all four quadrants; there is no quadrant free of tumor.
PRETEXT designations

Any group may have involvement of:

  • V—Vena cava or all three hepatic veins.
  • P—Main portal or portal bifurcation vein.
  • C—Caudate.
  • E—Extrahepatic contiguous.
  • M—Distant metastatic.
Hepatoblastoma and hepatocellular carcinoma prognosis by PRETEXT stage

The PRETEXT staging system has a moderate degree of interobserver variability, and the preoperative PRETEXT stage agrees with postoperative pathologic findings only 51% of the time, with overstaging in 37% of patients and understaging in 12% of patients.[3] The 5-year overall survival (OS) in the first international study of hepatoblastoma, in which the study protocol called for treatment of children with preoperative doxorubicin and cisplatin chemotherapy and included children with metastasis, was:

  • 100% for PRETEXT stage 1.
  • 91% for PRETEXT stage 2.
  • 68% for PRETEXT stage 3.
  • 57% for PRETEXT stage 4.
  • 25% for patients with metastasis.[5,6]

The second international study compared 3-year OS among hepatoblastoma patients by PRETEXT stage absent of extrahepatic disease:

  • 100% for PRETEXT stage 1.
  • 95% for PRETEXT stage 2.
  • 84% for PRETEXT stage 3.
  • 61% for PRETEXT stage 4.[7]

The study also prospectively analyzed OS in patients by the presence of intraabdominal extrahepatic disease without distant metastasis (58% OS) and distant metastases (44% OS).[7] Patients who underwent orthotopic liver transplant are included in all of the international study results.[8] The COG is investigating prospective staging of hepatoblastoma patients using the PRETEXT system to determine the timing of surgery and the timing of early notification of liver transplant centers (COG-AHEP0731 1).

The 5-year OS for PRETEXT staged hepatocellular carcinoma was:

  • 44% for PRETEXT stage 1.
  • 44% for PRETEXT stage 2.
  • 22% for PRETEXT stage 3.
  • 8% for PRETEXT stage 4.[9]
Postsurgical Staging for Childhood Liver Cancer

A staging system based on postsurgical extent of tumor and surgical resectability has been used in the United States to group children with liver cancer. This staging system is used to determine treatment.[10-12]

Hepatoblastoma prognosis by postsurgical stage

Stage I

Approximately 20% to 30% of children with hepatoblastoma are stage I and II.

  • No metastases, tumor completely resected.
    • Pure fetal histology (4% of hepatoblastomas) have a 3- to 5-year OS of 90% to 100% with minimal or no chemotherapy.[1,12]
    • Non-pure fetal histology, non-small cell undifferentiated (SCU) stage I and II hepatoblastomas have a 3- to 4-year OS of 90% to 100% with adjuvant chemotherapy.[1,5,7,12,13]
    • If any SCU elements are present in stage I or II hepatoblastoma, the 3-year survival is 40% to 70%.[1,14]
Stage II

Approximately 20% to 30% of children with hepatoblastoma are stage I and II.

  • No metastases, tumor grossly resected with microscopic residual disease (i.e., positive margins); or tumor rupture, or tumor spill at the time of surgery.
    • Pure fetal histology (4% of hepatoblastomas) have a 3- to 5-year OS of 90% to 100% with minimal or no chemotherapy.[1,12]
    • Non-pure fetal histology, SCU stage I and II hepatoblastomas have a 3- to 4-year OS of 90% to 100% with adjuvant chemotherapy.[1,5,7,12,13]
    • If any SCU elements are present in stage I or II hepatoblastoma, the 3-year survival is 40% to 70%.[1,14]
Stage III

Approximately 50% to 70% of children with hepatoblastoma are stage III.

  • No distant metastases, tumor unresectable or resected with gross residual tumor, or positive lymph nodes.
    • The overall 3- to 5-year survival for children with stage III hepatoblastoma is less than 70%.[1,5,7,12,15]
Stage IV

Approximately 10% to 20% of children with hepatoblastoma are stage IV.

  • Distant metastases regardless of the extent of liver involvement.
    • The overall 3- to 5-year survival for children with stage IV hepatoblastoma vary widely based on published reports, from 20% to approximately 60%.[1,5-7,12,15]
Hepatocellular carcinoma prognosis by postsurgical stage of disease at diagnosis
  • Children with stage I hepatocellular carcinoma have a good outcome.[16]
  • Stage II is too rarely seen to predict outcome.
  • Stages III and IV are usually fatal.[9,17]
Clinical Trials Under Evaluation: COG Hepatoblastoma Risk Groups

The COG study COG-AHEP0731 1 (Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Liver Cancer) incorporates the following risk groups:

  • Very low risk
    • Stage I tumor with pure fetal histology and an alpha-fetoprotein (AFP) level greater than 100 ng/ml.
  • Low risk
    • Stage I and II tumors and no SCU elements and an AFP level greater than 100 ng/ml.
  • Intermediate risk
    • Gross residual disease or unresectable disease.
    • Grossly resected disease with SCU elements.
    • No metastases.
    • AFP level must be greater than 100 ng/ml.
  • High risk
    • Any patient with metastases.
    • Any patient with initial AFP level less than 100 ng/ml, regardless of stage.

References

  1. Meyers RL, Rowland JR, Krailo M, et al.: Predictive power of pretreatment prognostic factors in children with hepatoblastoma: a report from the Children's Oncology Group. Pediatr Blood Cancer 53 (6): 1016-22, 2009.  [PUBMED Abstract]

  2. Brown J, Perilongo G, Shafford E, et al.: Pretreatment prognostic factors for children with hepatoblastoma-- results from the International Society of Paediatric Oncology (SIOP) study SIOPEL 1. Eur J Cancer 36 (11): 1418-25, 2000.  [PUBMED Abstract]

  3. Aronson DC, Schnater JM, Staalman CR, et al.: Predictive value of the pretreatment extent of disease system in hepatoblastoma: results from the International Society of Pediatric Oncology Liver Tumor Study Group SIOPEL-1 study. J Clin Oncol 23 (6): 1245-52, 2005.  [PUBMED Abstract]

  4. Roebuck DJ, Olsen Ø, Pariente D: Radiological staging in children with hepatoblastoma. Pediatr Radiol 36 (3): 176-82, 2006.  [PUBMED Abstract]

  5. Pritchard J, Brown J, Shafford E, et al.: Cisplatin, doxorubicin, and delayed surgery for childhood hepatoblastoma: a successful approach--results of the first prospective study of the International Society of Pediatric Oncology. J Clin Oncol 18 (22): 3819-28, 2000.  [PUBMED Abstract]

  6. Perilongo G, Brown J, Shafford E, et al.: Hepatoblastoma presenting with lung metastases: treatment results of the first cooperative, prospective study of the International Society of Paediatric Oncology on childhood liver tumors. Cancer 89 (8): 1845-53, 2000.  [PUBMED Abstract]

  7. Perilongo G, Shafford E, Maibach R, et al.: Risk-adapted treatment for childhood hepatoblastoma. final report of the second study of the International Society of Paediatric Oncology--SIOPEL 2. Eur J Cancer 40 (3): 411-21, 2004.  [PUBMED Abstract]

  8. Otte JB, Pritchard J, Aronson DC, et al.: Liver transplantation for hepatoblastoma: results from the International Society of Pediatric Oncology (SIOP) study SIOPEL-1 and review of the world experience. Pediatr Blood Cancer 42 (1): 74-83, 2004.  [PUBMED Abstract]

  9. Czauderna P, Mackinlay G, Perilongo G, et al.: Hepatocellular carcinoma in children: results of the first prospective study of the International Society of Pediatric Oncology group. J Clin Oncol 20 (12): 2798-804, 2002.  [PUBMED Abstract]

  10. Ortega JA, Krailo MD, Haas JE, et al.: Effective treatment of unresectable or metastatic hepatoblastoma with cisplatin and continuous infusion doxorubicin chemotherapy: a report from the Childrens Cancer Study Group. J Clin Oncol 9 (12): 2167-76, 1991.  [PUBMED Abstract]

  11. Douglass EC, Reynolds M, Finegold M, et al.: Cisplatin, vincristine, and fluorouracil therapy for hepatoblastoma: a Pediatric Oncology Group study. J Clin Oncol 11 (1): 96-9, 1993.  [PUBMED Abstract]

  12. Ortega JA, Douglass EC, Feusner JH, et al.: Randomized comparison of cisplatin/vincristine/fluorouracil and cisplatin/continuous infusion doxorubicin for treatment of pediatric hepatoblastoma: A report from the Children's Cancer Group and the Pediatric Oncology Group. J Clin Oncol 18 (14): 2665-75, 2000.  [PUBMED Abstract]

  13. Perilongo G, Maibach R, Shafford E, et al.: Cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma. N Engl J Med 361 (17): 1662-70, 2009.  [PUBMED Abstract]

  14. De Ioris M, Brugieres L, Zimmermann A, et al.: Hepatoblastoma with a low serum alpha-fetoprotein level at diagnosis: the SIOPEL group experience. Eur J Cancer 44 (4): 545-50, 2008.  [PUBMED Abstract]

  15. Zsíros J, Maibach R, Shafford E, et al.: Successful treatment of childhood high-risk hepatoblastoma with dose-intensive multiagent chemotherapy and surgery: final results of the SIOPEL-3HR study. J Clin Oncol 28 (15): 2584-90, 2010.  [PUBMED Abstract]

  16. Douglass E, Ortega J, Feusner J, et al.: Hepatocellular carcinoma (HCA) in children and adolescents: results from the Pediatric Intergroup Hepatoma Study (CCG 8881/POG 8945). [Abstract] Proceedings of the American Society of Clinical Oncology 13: A-1439, 420, 1994. 

  17. Katzenstein HM, Krailo MD, Malogolowkin MH, et al.: Hepatocellular carcinoma in children and adolescents: results from the Pediatric Oncology Group and the Children's Cancer Group intergroup study. J Clin Oncol 20 (12): 2789-97, 2002.  [PUBMED Abstract]



Table of Links

1http://www.cancer.gov/clinicaltrials/search/view?version=healthprofessional&
;cdrid=654889