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

Abstract

BACKGROUND: 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. OBJECTIVES: 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. DESIGN: Multi-centre retrospective cohort study of 236 patients treated with carboplatin AUC10 from January 2000 to December 2021. METHODS: 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. RESULTS: 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. CONCLUSION: 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.; Lower-intensity treatment using carboplatin AUC10 in metastatic good-risk seminoma: predictive factors and relapse patterns Why was the study done? Chemotherapy using cisplatin is the standard treatment for people with advanced testicular cancer, but it can cause significant side effects. An alternative treatment using a single drug, carboplatin (at a dose called AUC10), may be easier to tolerate while still being effective, especially for patients with a good outlook (good-risk seminoma). A recent international report found that high levels of a blood marker called LDH (lactate dehydrogenase) are linked to worse outcomes in patients treated with cisplatin. In this study, we looked at patients who were previously treated with carboplatin AUC10 to see how well they did over time. We focused on how often the cancer came back (relapsed) and whether certain factors, especially high levels of LDH were linked to worse outcomes. What did the researchers do? We reviewed medical records from two cancer centres in London. The study included patients with metastatic good-risk seminoma treated with carboplatin AUC10 between 2000 and 2021. We collected information such as age, cancer stage, tumour location, LDH levels, number of treatment cycles, whether the cancer relapse, further treatments and cause of death. What did the researchers find? We studied 236 patients over a median of 88 months. Only 6% of patients had their cancer relapse. After 5 years, 89% were cancer-free and 93% were still alive. Patients with high LDH levels had worse outcomes: after 5 years, 78% were cancer-free and 86% were still alive. Age and adding a fourth cycle of carboplatin did not improve outcomes. About half of the patients who relapsed could be successfully treated again. What do the findings mean? Carboplatin AUC10 remains an effective lower-intensity treatment for advanced testicular cancer. While high LDH may indicate a higher relapse risk, overall survival was still comparable to standard cisplatin treatment.