Cross-validation of a new prognostic index integrating tumor marker decline in patients with relapsed disseminated germ cell tumors

Abstract

5086 Background: Early serum tumor marker decline during chemotherapy was previously shown to be prognostic for progression-free survival (PFS) and overall survival (OS) in patients with relapsed GCT in an analysis of the IT94 phase III trial, which compared conventional chemotherapy versus high dose chemotherapy (Massard C, ASCO 2008. Abstract No. 5085). The aim of this study was to validate this concept in an independent set of patients. Methods: Data on tumor site, response to first line chemotherapy, serum tumor markers at baseline and after two cycles of chemotherapy were obtained from 235 patients accrued in the IT94 trial (training set) and from 181 patients included in phase III prospective trials of high-dose chemotherapy conducted by the German GCT group (Lorch et al, J Clin Oncol. 2007) (validation set). The change from baseline of serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) was assessed and classified into ‘favorable marker decline‘ and ‘unfavorable marker decline‘ group, as previously described (ASCO 2008. Abstract No. 5085). Results: In both series, favourable serum AFP decline was significantly associated with a better 2-year PFS (46% vs 24%; p < 0.0001) and OS (62% vs 34%; p = 0.0013) while serum hCG decline did not affect outcome. In multivariate analysis of the IT94 trial, an unfavorable AFP decline and a mediastinal primary site were adverse prognostic factors for both PFS and OS, and this was confirmed in the validation set. Among patients from the good prognostic group (favorable AFP decline and non-mediastinal primary site), those who were treated with high-dose chemotherapy had a better PFS (2-year PFS rate: 54% vs 37%; HR = 0.62; p = 0.017), and a trend for a better OS (2-year OS rate: 68% vs. 58%; HR = 0.77; p = 0.29) as compared to patients who were treated with conventional chemotherapy. In contrast, there was no difference in outcome in patients from the poor prognostic group (unfavourable AFP decline and/or mediastinal primary site), whether they received conventional chemotherapy or high-dose chemotherapy. Conclusions: AFP decline during the first 6 weeks of salvage chemotherapy and a mediastinal primary tumor site predict for PFS and OS in patients with relapsed disseminated GCT. No significant financial relationships to disclose.