Salvage High-Dose Chemotherapy for Relapsed Pure Seminoma in the Last 10 Years: Results From the European Society for Blood and Marrow Transplantation Series 2002-2012

In a retrospective analysis of data from 13 European Society for Blood and Marrow Transplantation (EBMT) centers, we evaluated the contemporary outcomes of high-dose chemotherapy (HDCT) as salvage therapy of advanced seminoma. The results supported the use of HDCT, particularly for patients with chemosensitive disease. This proof of concept needs to be prospectively validated in a randomized trial of HDCT versus standard-dose chemotherapy. Background: The optimal management of advanced seminoma that relapses after chemotherapy remains unknown. We retrospectively analyzed outcomes with the use of high-dose chemotherapy (HDCT). Patients and Methods: Eligibility included adult male patients with pure seminomatous histology and treatment with salvage HDCT. Data of patients who received HDCT from 13 European Society for Blood and Marrow Transplantation (EBMT) centers were used. Multivariable Cox analyses evaluated the association of prespecified factors (line of treatment, prior radiotherapy, and chemosensitivity according to standard definition), with progression-free (PFS) and overall survival (OS). The prognostic ability of the model was assessed through the concordance statistic. Results: From December 2002 to December 2012, 46 cases were identified. Median age was 38 years (interquartile range, 35-46 years). HDCT was provided as second-line therapy (n = 14, 30.4%) and in third-line or beyond third-line therapy (n = 20, 43.5%; 12 had missing information). Sixteen patients (34.8%) received paraortic and/or iliac radiotherapy, and 10 (21.7%) had disease that was cisplatin refractory or absolutely refractory. Median follow-up was 22 months (interquartile range, 8-56). On multivariable Cox analysis, refractory disease was a significantly negative prognostic factor for both PFS (hazard ratio, 6.04; 95% confidence interval, 1.86-19.64) and OS (hazard ratio, 3.93; 95% confidence interval, 1.07-14.45), while prior radiotherapy trended to significance for both. The c index was 0.74 and 0.66 for PFS and OS, respectively. The small numbers and the lack of any comparison with conventional-dose chemotherapy are major study limitations. Conclusion: Despite our small sample size, this retrospective analysis suggested that HDCT may represent a valuable therapeutic option for patients with a pure seminoma after standard-dose chemotherapy failure. Our observation requires validation through a prospective study.