OBJECTIVE: To compare the survival outcomes of de-escalation chemotherapy with those of standard first-line chemotherapy in patients with International Germ Cell Cancer Collaborative Group (IGCCCG) good prognosis metastatic seminoma. METHODS: The cohort of this retrospective, observational, single-center study comprised 35 patients with clinical Stage I (CSI)-relapsed or de novo IGCCCG good prognosis metastatic seminoma who had undergone induction chemotherapy at our institution between 2007 and 2021. Patients were allocated to standard or de-escalation therapy groups according to average relative dose intensity (ARDI) of induction chemotherapy: ARDI ≥ 90 and ARDI <
90. Overall and recurrence-free survival were compared between these groups using Kaplan-Meier curves and the log-rank test. RESULTS: The de-escalation therapy regimen included three cycles of etoposide and cisplatin (66.7%). Overall and relapse-free survival of patients undergoing de-escalation therapy and that of patients undergoing standard therapy were comparable. In addition, rates of adverse events, including hearing impairment and peripheral neuropathy induced by cisplatin-containing chemotherapy, were slightly, but not significantly, lower in the de-escalation therapy group than in the standard therapy group. CONCLUSIONS: Our findings provide a preliminary experimental basis for the development of de-escalation therapy for IGCCCG good prognosis metastatic seminoma. If sufficient tumor regression is achieved, de-escalation therapy incorporating three cycles of etoposide/cisplatin therapy could be considered acceptable for patients with relatively low metastatic tumor burdens, such as those with Stage II CSI-relapsed seminoma. Further studies to validate the efficacy of de-escalation therapy are warranted.