Treatment of patients with relapsed and/or cisplatin-refractory metastatic germ cell tumours: an update

Since the introduction of cisplatin-based therapy in the late 1970s, germ cell tumours (GCT) have been one of the successes in oncology with high cure rates even in patients presenting with metastatic disease. For patients with relapse after cisplatin-based therapy, treatment is still curative in approximately 50% of the cases. Management options for these patients include surgery, radiotherapy and use of conventional dose or high-dose chemotherapy (HDCT). Therefore, treatment of relapsed or refractory patients is complex and there is no uniformly accepted approach available. Data comparing conventional dose and HDCT in the first salvage therapy is limited to one randomized trial which was not able to ultimately define optimal treatment. More recently, a large retrospective analysis of nearly 1600 patients not only identified prognostic factors in relapse, but retrospectively suggested a 10-15% benefit regarding overall survival for patients receiving HDCT plus autologous stem cell transplantation over patients receiving conventional-dose chemotherapy. Prognosis in multiply relapsed and primary cisplatin-refractory patients is generally poor. Currently, a number of mechanisms of cisplatin resistance and potential drug targets like global methylation and BRAF mutation status are under investigation in refractory GCT.