The prognostic impact of different tumor marker levels in nonseminomatous germ cell tumor patients with intermediate prognosis: A registry of the International Global Germ Cell Tumor Collaborative Group (G3). BACKGROUND
 Germ cell tumor patients with intermediate prognosis (IPGCT) according to the International Germ Cell Cancer Collaborative Group (IGCCCG) classification represent a heterogeneous group with different clinical features.  This analysis was performed to investigate the prognostic impact of different tumor marker levels prior to first line chemotherapy within IPGCT.


 For this study an international registry for IPGCT was established.  Eligibility criteria were intermediate prognosis according to IGCCCG criteria, nonseminomatous histology, male sex, and age ≥ 16 years.  Uni- and multivariate analysis were conducted to identify characteristics associated with survival outcomes.  Receiver-Operating-Characteristic curve analysis was applied to find cut-off parameters.  Five-year overall survival (OS) rate was the primary and 5-year progression-free survival rate the secondary endpoint.


 This database included 634 IPGCT with a median follow-up of 9.0 years (interquartile range: 14.35).  Patients received first line treatment with platinum based chemotherapy, associated with a 5-year OS rate of 87%.  The stratification of patients according to AFP levels revealed a correlation between AFP levels and outcome, associated with 5-year OS rates of 88% for AFP levels <1,000 IU/ml (n = 303), 89% for 1,000 to 2,000 IU/ml (n = 82), 87% for >2,000 to 6,000 IU/ml (n = 121), and 82% for >6,000 IU/ml (n = 57) prior first course of chemotherapy, respectively (P= 0.013).  LDH levels prior fist course of chemotherapy also correlated with outcome associated with 5-year OS rates of 92% for <2 UNL (n = 271), 89% for ≥2 to 3 UNL (n = 85), 78% for >3 to 4 UNL (n = 34), and 77% for >4 UNL (n = 79), respectively (P= 0.03).  Different HCG levels prior chemotherapy were not associated with outcome.  In multivariable analysis AFP levels >6,000 IU/ml (P= 0.023; hazard ratio HR 2.263) or >1,982 IU/ml (P= 0.031; HR 1.722), and LDH levels >3 UNL (P< 0.001; HR 2.616) were independent prognosticators for OS.


 CONCLUSIONS
 Prognostication according to LDH and AFP levels prior chemotherapy could offer a new approach to stratify patients within the intermediate prognosis cohort.  According to our findings, patients with AFP values above 6,000 IU/ml or/and LDH > 3 UNL represent an independent high risk cohort.  Our results need to be confirmed in the upcoming IGCCCG reclassification.
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