Early Predicted Time to Normalization of Tumor Markers Predicts Outcome in Poor-Prognosis Nonseminomatous Germ Cell Tumors

Abstract

Purpose The prognostic relevance of the rate of decline of serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) during the first 3 weeks of chemotherapy for nonseminomatous germ cell tumors (NSGCT) was studied in the context of the International Germ Cell Cancer Collaborative Group (IGCCCG) classification. Patients and Methods Data from 653 patients prospectively recruited in clinical trials were studied. Tumor markers were obtained before chemotherapy and 3 weeks later. Decline rates were calculated using a logarithmic formula and expressed as a predicted time to normalization (TTN). A favorable TTN was defined when both AFP and HCG had a favorable decline rate, including cases with normal values. Results The median follow-up was 50 months (range, 2 to 151 months). Tumor decline rate expressed as a predicted TTN was associated with both progression-free survival (PFS; P < .0001) and overall survival (OS; P < .0001). The 4-year PFS rates were 64% and 38% in patients from the poor-prognosis group who had a favorable and an unfavorable TTN, respectively. The 4-year OS rates were 83% and 58%, respectively. This effect was independent from the initial tumor marker values, the primary tumor site, and the presence of nonpulmonary visceral metastases: tumor marker decline rate remained a strong predictor for both PFS (hazard ratio = 2.5; P = .01) and OS (hazard ratio = 4.6; P = .002) in patients from the IGCCCG poor-prognosis group in multivariate analysis. Conclusion Early predicted time to tumor marker normalization is an independent prognostic factor in patients with poor-prognosis NSGCT and may be a useful tool in the therapeutic management of these patients.