Cancer Treatment Today

High dose chemotherapy with autologous stem cell rescue is an accepted and standard of care approach for relapsed or nonresponding testicular cancer. It is recommended by several guidelines, including NCCN.

Extragonadal germinal cell syndromes are rare tumors that predominantly affect young males. Histologically, they mirror their gonadal counterparts with which they share the same chemosensitivity and radiosensitivity. Controversy remains regarding the origin of extragonadal germ cell tumors (EGGCTs). The classic theory suggests that germ cell tumors (GCTs) in these areas are derived from local transformation of primordial germ cells misplaced during embryogenesis but a recent alternative theory suggests that primary mediastinal presentations represent reverse migration of occult carcinoma in situ (CIS) lesions in the gonad; hence, they may be gonadal in origin. Some retroperitoneal extragonadal germ cell tumors may represent metastases from a testicular cancer, with subsequent spontaneous necrosis of the primary tumour.

For patients receiving intensive chemotherapy, 5-year survival rates of 40-65% have been reported.The mediastinum is the most common site of extragonadal germ cell tumors. Mediastinal germ cell tumors account for only 2-5% of all germinal tumors, but they constitute 50-70% of all extragonadal tumors. Treatment with 4 cycles of bleomycin, etoposide, and cisplatin (BEP) is the current standard of care. Radiotherapy or surgery can be used after chemotherapy in bulky mediastinal seminomas. Among those whose disease relapses after or progressed on first-line chemotherapy, or those in high risk, or whose disese could not be resected, surgery shuld be attmepted. Otherwise, it is rare to achieve complete remission despite salvage therapy with cisplatin-based regimens, high-dose chemotherapy, paclitaxel, or oral etoposide. High dose therapy is the best hope for these patients, but it is not yet etablished and continues to be investigated, for example: Paclitaxel, Ifosfamide, and Carboplatin Followed By Autologous Stem Cell Transplant in Treating Patients With Germ Cell Tumors That Did Not Respond to Cisplatin, NCT00423852.

A randomized controlled trial compared conventional doses of salvage chemotherapy to high-dose chemotherapy with autologous marrow rescue in 263 patients with recurrent or refractory germ cell tumors. Of the 263 patients, 43 of whom had extragonadal primary tumors, more toxic effects and treatment-related deaths were seen in the high-dose arm without any improvement in response rate or overall survival. One would have to consider transplantation as investigational at this time for this disease.

H. J. Schmoll, R. Souchon, S. Krege, P. Albers, J. Beyer, C. Kollmannsberger, S. D. Fossa, N. E. Skakkebaek, R. de Wit, K. Fizazi, et al.
European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG)
Ann. Onc., September 1, 2004; 15(9): 1377 – 1399.

H. J. Schmoll, R. Souchon, S. Krege, P. Albers, J. Beyer, C. Kollmannsberger, S. D. Fossa, N. E. Skakkebaek, R. de Wit, K. Fizazi, et al.
European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG)
Ann. Onc., September 1, 2004; 15(9): 1377 – 1399.

Pico JL, Rosti G, Kramar A, et al.: A randomised trial of high-dose chemotherapy in the salvage treatment of patients failing first-line platinum chemotherapy for advanced germ cell tumours. Ann Oncol 16 (7): 1152-9, 2005.