Treatment de-escalation for metastatic good-risk seminoma with carboplatin AUC10: predictive factors and patterns of relapse

We have previously demonstrated that carboplatin AUC10 is a viable alternative to cisplatin-based combination chemotherapy for patients with metastatic good-risk seminoma. The International Germ Cell Cancer Collaborative Group (IGCCCG) update identified lactate dehydrogenase (LDH) as an adverse prognostic marker in those receiving cisplatin-based therapies but its relevance in patients treated with carboplatin AUC10 is unknown. To update survival outcomes of patients treated with carboplatin AUC10, explore patterns of treatment relapse and determine the impact of clinical and biochemical factors on oncological outcomes. Multi-centre retrospective cohort study of 236 patients treated with carboplatin AUC10 from January 2000 to December 2021. Clinical parameters including age, stage, number of cycles delivered, primary tumour location, LDH level, relapse date, post-relapse treatment and cause of death were extracted. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method and event-time distributions were compared using the log-rank test. Variables predictive of PFS and OS were identified using Cox proportional hazards model. The primary tumour site was testis in 95% (n = 225) of patients. Stage distribution was II (86%, n = 204) and III (14%, n = 32). Fourteen patients (6%) relapsed with 11 receiving salvage bleomycin, etoposide and cisplatin. Updated 5-year PFS and OS were 89% and 93%, respectively, over a median follow-up of 88 months. Twenty-three patients (10%) had LDH ⩾2.5 upper limit normal, with 5-year PFS and OS of 78% and 86%, respectively. Age was not associated with risk of relapse. The addition of a fourth cycle of carboplatin was not associated with better outcomes even after adjusting for other risk factors on multivariate analysis. Approximately 50% of relapsed patients were successfully salvaged. Carboplatin AUC10 remains an effective de-escalation regimen for metastatic seminoma, with robust survival rates at prolonged follow-up. Elevated LDH indicates poorer oncological outcomes with carboplatin AUC10, though survival remained comparable to cisplatin-based chemotherapy.