Childhood Extracranial Germ Cell Tumors Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Treatment of Malignant Extragonadal Extracranial GCTs in Children

Extragonadal extracranial germ cell tumors (GCTs) (i.e., sacrococcygeal, mediastinal, and retroperitoneal) are more common in children than in adults.[1] Children with extragonadal malignant GCTs, particularly those with advanced-stage disease, have the highest risk of treatment failure for any GCT presentation.[2,3]

In a study of prognostic factors in pediatric extragonadal malignant GCTs, age older than 12 years was the most important prognostic factor. In a multivariate analysis, children aged 12 years or older with thoracic tumors had six times the risk of death compared with children younger than 12 years with primary nonthoracic tumors.[4]

Standard Treatment Options for Malignant Extragonadal Extracranial GCTs

Standard treatment options for malignant extragonadal extracranial GCTs include the following:

  1. Surgery and chemotherapy.
  2. Biopsy followed by chemotherapy and possibly surgery.

Outcome has improved remarkably since the advent of platinum-based chemotherapy and the use of a multidisciplinary treatment approach.[2,5] Complete resection before chemotherapy may be possible in some patients without major morbidity. For patients with locally advanced sacrococcygeal tumors, mediastinal tumors, or large pelvic tumors, tumor biopsy followed by preoperative chemotherapy can facilitate subsequent complete tumor resection and improve ultimate patient outcome.[5,6,7,8]

The role for surgery at diagnosis for extragonadal tumors is age- and site-dependent and must be individualized. Depending on the clinical setting, the appropriate surgical approach may be primary resection, biopsy before chemotherapy, or no surgery (e.g., mediastinal primary tumor in a patient with a compromised airway and elevated tumor markers). An appropriate strategy may be biopsy at diagnosis followed by chemotherapy and subsequent surgery in selected patients who have residual masses after chemotherapy.

Stages I and II

Surgery and chemotherapy with four to six cycles of standard cisplatin, etoposide, and bleomycin (PEB) is one treatment alternative. Patients treated with this regimen have an overall survival (OS) outcome greater than 90%, suggesting that a reduction in therapy could be considered.[2,9] An alternative treatment option is surgery and chemotherapy with six cycles of carboplatin, etoposide, and bleomycin (JEB).[5]

Stages III and IV

A treatment option for stage III and stage IV disease is surgery and chemotherapy with four to six cycles of standard PEB. These patients have an OS outcome approaching 80% with this regimen.[2] Another treatment option is surgery and chemotherapy with six cycles of JEB, which has a similar OS to the PEB regimen.[5]


A Children's Oncology Group trial investigated the addition of cyclophosphamide to standard-dose PEB. The addition of cyclophosphamide was feasible and well tolerated at all dose levels, but there was no evidence that adding cyclophosphamide improves efficacy.[10]

Malignant Extragonadal Extracranial GCTs (Sacrococcygeal Sites)

Sacrococcygeal GCTs are common extragonadal tumors that occur in very young children, predominantly young females.[11] The tumors are usually diagnosed at birth, when large external lesions predominate (usually mature or immature teratomas), or later in the first years of life, when presacral lesions with higher malignancy rates predominate.[11]

Malignant sacrococcygeal tumors are usually very advanced at diagnosis; two-thirds of patients have locoregional disease, and metastases are present in 50% of patients.[7,12,13] Because of their advanced stage at presentation, the management of sacrococcygeal tumors requires a multimodal approach with platinum-based chemotherapy followed by delayed tumor resection.

Platinum-based therapies, with either cisplatin or carboplatin, are the cornerstone of treatment. The PEB regimen or the JEB regimen produces event-free survival (EFS) rates of 75% to 85% and OS rates of 80% to 90%.[7,8] Surgery may be facilitated by preoperative chemotherapy. In any patient with a sacrococcygeal GCT, resection of the coccyx is mandatory.[7,8]

Completeness of surgical resection is an important prognostic factor, as shown in the following circumstances:[7,8]

  • Resected tumors with negative microscopic margins-EFS rates of greater than 90%.
  • Resected tumors with microscopic margins-EFS rates of 75% to 85%.
  • Resected tumors with macroscopic residual disease-EFS rates of less than 40%.

Malignant Extragonadal Extracranial GCTs (Mediastinal)

Mediastinal GCTs account for 15% to 20% of malignant extragonadal extracranial GCTs in children.[5] The histology of mediastinal GCT is dependent on age, with teratomas predominating among infants and yolk sac tumor histology predominating among children aged 1 to 4 years.[6]

Children with mediastinal teratomas are treated with tumor resection, which is curative in almost all patients.[6] Children with malignant, nonmetastatic mediastinal GCTs who receive cisplatin-based chemotherapy have 5-year EFS and OS rates of 90%; however, metastatic mediastinal tumors have an EFS closer to 70%.[5,6]


Most mediastinal GCTs in adolescents and young adults occur in males, and 22% to 50% have cytogenetic changes consistent with Klinefelter syndrome.[14,15] The age of presentation is younger in patients with Klinefelter syndrome.[14,15] As with sacrococcygeal tumors, primary chemotherapy is usually necessary to facilitate surgical resection of mediastinal GCTs, and the completeness of resection is a very important prognostic indicator.[6,16] Survival rates for the older adolescent and young adult population with mediastinal tumors are generally less than 60%.[4,17,18,19]; [20][Level of evidence: 3iiA]

Patients with a malignant mediastinal primary tumor and extracranial metastases are at the highest risk of developing brain metastases and are monitored closely for signs and symptoms of central nervous system involvement.[21][Level of evidence: 3iiB] (Refer to the PDQ summary on Extragonadal Germ Cell Tumors Treatment for more information about the treatment of adult patients.)

Malignant Extragonadal Extracranial GCTs (Retroperitoneum)

Malignant GCTs located in the retroperitoneum or abdomen usually present in children before the age of 5 years; most tumors are of advanced stage and locally unresectable at diagnosis.[22] A limited biopsy followed by platinum-based chemotherapy to shrink tumor bulk can lead to complete tumor resection in most patients. Despite the advanced-stage disease in most patients, the 6-year EFS using PEB was 83% in the Pediatric Oncology Group/Children's Cancer Group intergroup study.[22]

Malignant Extragonadal Extracranial GCTs (Head and Neck Sites)

Although rare, benign and malignant GCTs can occur in the head and neck region, especially in infants. Often the airway is threatened. Surgery for nonmalignant tumors and surgery plus chemotherapy for malignant tumors can be curative.[23][Level of evidence: 3iiiDii]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with childhood extragonadal germ cell tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.


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