Background: The optimal salvage therapy for relapsed germ cell tumors (GCTs) remains undefined and the optimal timing for high-dose chemotherapy (HD-CT) is unclear. We analyzed data from the European Society for Blood and Marrow Transplantation registry to evaluate contemporary outcomes in patients treated with HD-CT across salvage lines. Patients and methods: We extracted data of adult males with GCTs (excluding mediastinal primary) who received one or more courses of HD-CT with carboplatin and etoposide between 2000 and 2022. Patients treated within 3 months from diagnosis were excluded, as this was considered upfront therapy. Time from diagnosis to first HD-CT (TT) was categorized in 3-6, 6-12, and >12 months. A Cox model with restricted cubic splines was used to evaluate the nonlinear effect of TT on survival. Results: Data from a total of 2204 patients were analyzed. Histology was available for 1074, of whom 69% had nonseminoma. Among 969 patients with primary site information, 69% had testicular GCT. International Prognostic Factors Study Group (IPFSG) categories were available for 500 patients: 17% very high, 38% high, 31% intermediate, 10% low, and 3.6% very low risk. TT was 3-6 months for 280 (13%), 6-12 months for 831 (38%), and >12 months for 1093 (50%). Of the patients, 1118 (51%) received three cycles of HD-CT. Median overall survival (OS) and progression-free survival (PFS) were 36.4 [95% confidence interval (CI) 30.3-58.7] and 9.9 months (95% CI 8.5-12.4), respectively. Spline analysis showed increasing hazard of progression and death with longer TT. No interaction was observed between TT and IPFSG risk for PFS (P = 0.62), whereas a significant interaction was found for OS (P = 0.04) in non–high-risk patients. Conclusions: In the largest contemporary series of salvage HD-carboplatin–etoposide in GCTs, HD-CT was effective regardless of TT as a surrogate of salvage line, with a significant interaction in non–high-risk patients, suggesting a nonlinear association between HD-CT timing and OS.
Contemporary outcomes of salvage high-dose chemotherapy in advanced germ cell tumors: an analysis of the cellular therapy and immunobiology working party of the EBMT registry / Tateo, V., Longoni, M., Secondino, S., Llorente, C.C., Nicholson, E., Lanza, F., De Giorgi, U., Burchert, A., Stelljes, M., Bandini, M., Badoglio, M., Rosti, G., Kuball, J., Malard, F., Ruggeri, A., Pedrazzoli, P., Necchi, A.. - In: ESMO OPEN. - ISSN 2059-7029. - (2026). [Epub ahead of print] [10.1016/j.esmoop.2026.108365]
Contemporary outcomes of salvage high-dose chemotherapy in advanced germ cell tumors: an analysis of the cellular therapy and immunobiology working party of the EBMT registry
Bandini M.;Necchi A.Ultimo
2026-01-01
Abstract
Background: The optimal salvage therapy for relapsed germ cell tumors (GCTs) remains undefined and the optimal timing for high-dose chemotherapy (HD-CT) is unclear. We analyzed data from the European Society for Blood and Marrow Transplantation registry to evaluate contemporary outcomes in patients treated with HD-CT across salvage lines. Patients and methods: We extracted data of adult males with GCTs (excluding mediastinal primary) who received one or more courses of HD-CT with carboplatin and etoposide between 2000 and 2022. Patients treated within 3 months from diagnosis were excluded, as this was considered upfront therapy. Time from diagnosis to first HD-CT (TT) was categorized in 3-6, 6-12, and >12 months. A Cox model with restricted cubic splines was used to evaluate the nonlinear effect of TT on survival. Results: Data from a total of 2204 patients were analyzed. Histology was available for 1074, of whom 69% had nonseminoma. Among 969 patients with primary site information, 69% had testicular GCT. International Prognostic Factors Study Group (IPFSG) categories were available for 500 patients: 17% very high, 38% high, 31% intermediate, 10% low, and 3.6% very low risk. TT was 3-6 months for 280 (13%), 6-12 months for 831 (38%), and >12 months for 1093 (50%). Of the patients, 1118 (51%) received three cycles of HD-CT. Median overall survival (OS) and progression-free survival (PFS) were 36.4 [95% confidence interval (CI) 30.3-58.7] and 9.9 months (95% CI 8.5-12.4), respectively. Spline analysis showed increasing hazard of progression and death with longer TT. No interaction was observed between TT and IPFSG risk for PFS (P = 0.62), whereas a significant interaction was found for OS (P = 0.04) in non–high-risk patients. Conclusions: In the largest contemporary series of salvage HD-carboplatin–etoposide in GCTs, HD-CT was effective regardless of TT as a surrogate of salvage line, with a significant interaction in non–high-risk patients, suggesting a nonlinear association between HD-CT timing and OS.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
