PDQ® Treatment Health Professionals
Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. Refer to the PDQ levels of evidence summary for more information.
Extragonadal germ cell tumors are rare and account for only a small percentage of all germ cell tumors. However, the true incidence of these tumors may conceivably be higher than originally thought because of failure to diagnose them properly.
Extragonadal germ cell tumors can be benign (teratoma) or malignant. The latter group can be divided into seminoma and nonseminoma, which includes embryonal carcinoma, malignant teratoma, endodermal sinus tumor, choriocarcinoma, and mixed germ cell tumors. Although much more common in males, they also occur in females. They are usually seen in young adults and are aggressive neoplasms. They can arise virtually anywhere, but typically the site of origin is in the mid-line (mediastinum, retroperitoneum, or pineal gland). Gonadal origin should be excluded by careful testicular examination and ultrasound. The diagnosis can be difficult and should be considered in any patient with a poorly defined epithelial malignancy, particularly young individuals with mid-line masses.[2,3]
Benign teratomas are treated with surgical excision only. These tumors are frequently very large, and the surgical procedure can be formidable.
The diagnosis of seminoma requires that the serum alpha fetoprotein (AFP) be normal and no other germ cells be present. Management decisions in these patients can sometimes be difficult. As in testicular seminoma, these tumors are very radiosensitive. About 60% to 80% will remain disease free after radiation. However, initial chemotherapy with regimens used in nonseminoma testis cancer is also very efficacious. Practically speaking, patients with localized relatively small tumors are usually treated initially with radiation, while those with very bulky tumors or nonlocalized tumors are treated with etoposide- and cisplatin-based chemotherapy regimens.
As in testicular seminoma, many will be left with a residual mass after treatment. If the residual mass is smaller than 3.0 centimeters, nearly all would agree that observation is appropriate. In those with larger residual masses, some groups favor surgical excision while others favor observation.[5,6]
Patients with nonseminomas should receive chemotherapy at diagnosis. These patients tend to have a very large tumor volume at diagnosis and are usually symptomatic. Initial debulking surgery is rarely useful. Many high-risk patients qualify for ongoing trials, such as randomized studies comparing high- dose chemotherapy plus hematopoietic rescue to "standard" therapy. "Standard" therapy would generally be considered to be four courses of bleomycin, etoposide, and cisplatin (BEP).[8,9] A randomized study comparing four courses of BEP to four courses of VIP (etoposide + ifosfamide + cisplatin) showed equivalent overall survival and time-to-treatment failure for the two regimens in patients with advanced disseminated germ cell tumors who had not received prior chemotherapy.[Level of evidence: 1iiA] Of the 204 patients on this study, 66 had extragonadal primary tumors, and responses in this subset of patients were similar on the two regimens. Hematologic toxic effects in the overall study were substantially worse with the VIP regimen compared to the BEP regimen. Those patients with normal markers and a residual mass after chemotherapy should undergo postchemotherapy surgery with resection of all residual disease. Patients with nonseminomatous extragonadal germ cell tumors who relapse after front-line chemotherapy generally have a poor prognosis with a poor response to salvage chemotherapy regimens, including autologous bone marrow transplantation, that have had success for recurrent testicular cancer.[11-13] Therefore, such patients are candidates for studies of new approaches.
Mediastinal nonseminomas have certain unique aspects. They are more frequent in individuals with Klinefelter's syndrome and are associated with a risk of subsequent development of hematologic neoplasia that is not treatment related.[14,15] Approximately 50% will survive with appropriate management. High risk is partially related to tumor bulk, to chemotherapy resistance, and to a predisposition to develop hematologic neoplasia and other non-germ cell malignancies.
The prognosis of retroperitoneal nonseminoma is reasonably good and, similar to the situation with nodal metastasis from a testicular primary, is related to tumor volume.
An international germ cell tumor prognostic classification has been developed based on a retrospective analysis of 5,202 patients with metastatic nonseminomatous and 660 patients with metastatic seminomatous germ cell tumors. All patients received treatment with cisplatin- or carboplatin- containing therapy as their first chemotherapy course. The prognostic classification, shown below, was agreed on in early 1997 by all major clinical trial groups worldwide. It should be used for reporting of clinical trials results of patients with extragonadal germ cell tumors.
--Good Prognosis-- Nonseminoma: testis/retroperitoneal primary and no non-pulmonary visceral metastases and good markers - all of: AFP<1000 ng/ml and hCG<5000 iu/l (1000 ng/ml) and LDH<1.5 x upper limit of normal 56% of nonseminomas 5 year progression-free survival (PFS) 89% 5 year survival 92% Seminoma: Any primary site and no non-pulmonary visceral metastases and normal AFP, any hCG, any LDH 90% of seminomas 5 year PFS 82% 5 year survival 86% --Intermediate Prognosis-- Nonseminoma: testis/retroperitoneal primary and no non-pulmonary visceral metastases and intermediate markers - any of: AFP>/=1000 and </=10,000 ng/mL or hCG>/=5000 iu/l and </=50,000 iu/l or LDH>/=1.5 x N and </=10 x N 28% of nonseminomas 5 year PFS 75% 5 year survival 80% Seminoma: any primary site and non-pulmonary visceral metastases and normal AFP, any hCG, any LDH 10% of seminomas 5 year PFS 67% 5 year survival 72% --Poor Prognosis-- Nonseminoma: mediastinal primary or non-pulmonary visceral metastases or poor markers - any of: AFP>10,000 ng/ml or hCG>50,000 iu/l (1000 ng/ml) or LDH>10 x upper limit of normal 16% of nonseminomas 5 year PFS 41% 5 year survival 48% Seminoma: No patients classified as poor prognosis.
Date Last Modified: 05/1999