Intermediate prognosis in metastatic germ cell tumors (IPGCT): Outcome and prognostic stratification

Background: Germ cell tumor patients with intermediate prognosis (IPGCT) according to the IGCCCG classification represent a heterogeneous group exhibiting a variety of clinical features. We established a registry to identify prognostic markers to further characterize IPGCT. Methods: A retrospective observational study was performed. Eligibility criteria were intermediate prognosis according to IGCCCG criteria, male sex, age ≥16 years. Patients were diagnosed from 1979 to 2014. Clinical characteristics were evaluated with uni- and multivariate analyses to detect new prognosticators. AFP and HCG were available in 85% and LDH levels in 72% of the cases, respectively. Overall survival (OS) was the primary endpoint. Results: The database included n = 707 IPGCT with a median follow-up of 8.6 years (IQR: 14.4). First line cisplatin-based chemotherapy was administered to 701 patients (99%) and the 5-year OS rate was 87%. First diagnosis in the 1980s (n = 115), the 1990s (n = 158), and after 2000 (n = 434) were associated with 5-year OS rates of 81%, 85%, and 89%, respectively. Statistical analyses revealed AFP and LDH, but not HCG levels prior chemotherapy as prognosticators. A patient stratification according to AFP levels <1000 IU/ml (n = 360), 1000 to 2000 IU/ml (n = 77), >2000 to 5000 IU/ml (n = 93) and >5000 (n = 74) IU/ml prior first course of chemotherapy, revealed a significant correlation between AFP levels and OS, associated with 5-year OS rates of 89%, 87%, 86% and 82%, respectively (p = 0.037). LDH levels prior chemotherapy also correlated with outcome, associated with five-year OS rates of 92% for <2 ULN (n = 289), 88% for ≥2 to 3 ULN (n = 91), 80% for >3 to 4 ULN (n = 37), and 78% for >4 ULN (n = 89), respectively (p = 0.011). In multivariate analysis cut-off values of AFP levels >6000 IU/ml (p = 0.036; HR 2.096) and LHD levels >2 ULN (p = 0.02; HR 2.121) or > 3 ULN (p = <0.001; HR 2.305) were independent prognosticators for OS. Conclusions: Prognostication according to LDH and AFP levels prior chemotherapy could offer a new approach to stratify IPGCT. The largest fraction of patients had AFP levels <2000 IU/ml and LDH <2 ULN associated with an outcome similar to the good prognosis category. These results need to be confirmed in the upcoming IGCCCG reclassification.