Balancing efficacy with long-term side-effects: can we safely de-escalate therapy for germ cell tumors?

INTRODUCTION: The success in the management of germ cell tumors has encouraged researchers to pay more attention on long-term side effects and other survivorship issues. The de-escalation of treatment is intended to reduce side effects but must be balanced against any compromise of efficacy. Cisplatin-based therapy is the cornerstone of treatment for germ cell tumors. However, they can result in acute and long-term side effects, including ototoxicity, neurotoxicity, nephrotoxicity, and increased risk of second malignancies. AREAS COVERED: This review discusses approaches of de-escalation including biomarker-directed treatment using microRNAs, surveillance for immature teratoma, the use of carboplatin monotherapy for seminoma, and the option of non-cisplatin-based approaches in relapsed germ cell tumors. EXPERT OPINION: While the results with the current standard options in terms of cancer control are very good, the price being paid in terms of long-term side effects is considerable.