Prolonged survival in patients with persistently elevated tumor markers after chemotherapy for nonseminomatous germ cell cancer

Abstract

5051 Background: Persistently elevated levels of either AFP or HCG or both after chemotherapy are thought to represent residual viable disease while the normalization of tumor markers predicts favorable outcomes. This study was to evaluate the clinical implication of tumor marker normalization for disseminated nonseminomatous germ cell tumors (GCTs). Methods: This was a retrospective data analysis from two prospective randomized trials (ECOG E4887 and E3887). In E4887, 178 patients with minimal- or moderate-stage disease (Indiana stage) were randomized to receive three cycles of cisplatin plus etoposide with/without bleomycin. In E3887, 304 patients with advanced disseminated GCTs were randomized to receive four cycles of bleomycin, etoposide and cisplatin versus the combination of etoposide, ifosfamide and cisplatin. AFP and HCG were assessed at baseline and after each cycle of chemotherapy. Tumor marker normalization was defined as AFP or HCG normalized after completing chemotherapy. OS and PFS curves were estimated by the Kaplan-Meier method. Multivariate and univariate models, stratified on International Germ Cell Consensus Classification (IGCCCG), were used to assess the impact of marker normalization for patients with abnormal markers at study entry. Results: Median follow-up is 14.8 years. About 40% to 60% of Patients with persistently elevated AFP or HCG after chemotherapy have prolonged PFS and/or OS. In IGCCCG poor risk patients, 35% to 55% of them with persistently elevated AFP or HCG after chemotherapy have prolonged PFS and/or OS. There is a statistically significant difference in OS associated with AFP normalization in both multivariate (p=0.008, HR=0.51 with 95% CI=0.31–0.84) and univariate analysis (p=0.0008, HR=0.43 with 95% CI=0.26–0.71). However, there was no statistically significant difference in OS associated with normalization of HCG in both multivariate analysis (p=0.52, HR=0.84 with 95% CI=0.50–1.41) and univariate analysis (p=0.29, HR=0.76 with 95% CI=0.46–1.26). Conclusions: Patients with persistently elevated AFP or HCG after chemotherapy may still have prolonged PFS and/or OS. Normalization of AFP but not HCG is associated with better OS in patients with disseminated nonseminomatous GCTs. No significant financial relationships to disclose.