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)

Urol Oncol. 2019 Nov;37(11):809.e19-809.e25. doi: 10.1016/j.urolonc.2019.07.020. Epub 2019 Sep 5.


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.

Methods: 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.

Results: 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.

Keywords: AFP and LDH levels; IGCCCG classification; Intermediate prognosis; Risk factor stratification.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / blood*
  • Humans
  • L-Lactate Dehydrogenase / blood
  • Male
  • Middle Aged
  • Neoplasms, Germ Cell and Embryonal / blood*
  • Neoplasms, Germ Cell and Embryonal / drug therapy
  • Neoplasms, Germ Cell and Embryonal / mortality
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Platinum / therapeutic use
  • Prognosis
  • Progression-Free Survival
  • Registries*
  • Survival Rate
  • Testicular Neoplasms / blood*
  • Testicular Neoplasms / drug therapy
  • Testicular Neoplasms / mortality
  • Testicular Neoplasms / pathology
  • Young Adult
  • alpha-Fetoproteins / analysis


  • AFP protein, human
  • Biomarkers, Tumor
  • alpha-Fetoproteins
  • Platinum
  • L-Lactate Dehydrogenase

Supplementary concepts

  • Nonseminomatous germ cell tumor