ESMO 2019: Prognostic Factors in Metastatic Seminomatous Germ Cell Tumors and Elevated HCG – a Study of the G3

Barcelona, Spain ( Seminomas do not express specific tumor markers, but in ∼20% of patients, serum HCG levels are elevated. The prognostic role of different marker levels at first diagnosis has not been thoroughly assessed. The objective of the current study was to assess prognostic factors in HCG positive seminoma patients. A presentation from Dr. Christoph Seidel and colleagues at the 2019 European Society for Medical Oncology annual meeting, (ESMO).

For this study, patients with seminomatous histology, metastatic disease, serum HCG levels above normal without AFP elevations at diagnosis were eligible. Univariable and multivariable analyses were conducted to identify risk factors associated with survival outcomes. Cut-off values were determined by ROC curve analysis. The primary endpoint was overall survival (OS) and the secondary endpoint was recurrence free survival (RFS).

There were 392 eligible patients identified and diagnosed between 1984 and 2018, and 82% were good risk, 12% were intermediate risk, and 6% had missing information. The median age was 39.5 years (range 17-79), the median HCG pre-orchiectomy was 33 IU/l (range >2 to 280,000), and the median HCG post-orchiectomy was 37 IU/l (range 0 to 36,000). The 5-year OS and 3-year RFS rates were 91% and 83%, respectively. Serum HCG levels pre-orchiectomy correlated with the UICC stage: mean HCG 826.9 IU/l in stage IIA-C vs. mean 4764.4 IU/l in stage IIIA-C (p < 0.001), and metastatic burden assessed by the largest axial diameter of metastasis: mean HCG 57.4 IU/l if < 7cm vs. mean 4,685 IU/l if ≥ 7cm (p = 0.012). Univariable analysis revealed LDH ≥1.5 upper limit of normal (UNL) pre-orchiectomy (5-year OS: 87% vs. 97%, n = 91) (p = 0.019), age ≥40 years (5-year OS: 87% vs. 94%, n = 152) (p = 0.007), and HCG ≥ 2,000 IU/l pre-orchiectomy (5-year OS: 76% vs. 94%, n = 17) (p = 0.019) as poor prognostic factors concerning OS. Multivariable analysis confirmed LDH ≥1.5 UNL pre-orchiectomy (HR 3.88, 95%CI 1.97-16.25; p = 0.01), age ≥40 years (HR 5.97, 95%CI 1.82-17.15; p = 0.02), and HCG levels ≥2,000 IU/l pre-orchiectomy (HR 3.59, 95%CI 1.01-12.77; p = 0.048) as independent negative prognosticators for OS. No significant correlations were found between patient characteristics and the recurrence free survival.


The main limitation of this study is the small sample size of patients in the ≥2,000 IU/l pre-orchiectomy group (n=17), leading to wide confidence intervals in the multivariable analysis. Dr. Seidel concluded that HCG values correlate with the tumor stage and levels ≥2,000 IU/l are associated with an impaired outcome concerning OS. He also concluded that the results should be considered for the risk stratification of HCG positive seminoma patients, however this should first be validated in a larger subset of patients.

Presented by: Christoph Seidel, Priv.-Doz. Dr. med, UKE Universitätsklinikum Hamburg-Eppendorf KMTZ, Hamburg, Germany

Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 2019 European Society for Medical Oncology annual meeting, ESMO 2019 #ESMO19, 27 Sept - 1 Oct 2019 in Barcelona, Spain