4447 - Prognostic factors in metastatic seminomatous germ cell tumors and elevated human chorionic gonadotrophin (HCG) – a study of the G3

Background

Seminomas do not express specific tumour markers, but in ∼30% of the patients (pts) serum HCG levels are elevated. This study investigates the prognostic impact of HCG levels and other characteristics in metastatic HCG-positive seminoma patients.

Methods

Patients with seminomatous histology, metastatic disease, serum HCG levels above normal without AFP elevations at diagnosis were eligible. Uni- and multivariable analyses were conducted to identify risk factors associated with survival outcomes. Cut-off values were determined by ROC curve analysis. Primary and secondary endpoints were overall survival (OS) and recurrence free survival (RFS), respectively.

Results

Our study identified 407 eligible patients diagnosed between 1984 and 2018 (334 pts good and 48 pts intermediate prognosis according to IGCCCG). The 5-year OS and 3-year RFS rates were 91% and 83%, respectively. HCG levels ranged from 1 IU/l to 283.782 IU/l (median: 33; IQR 142.5) pre- and 0 IU/l to 36.700 IU/l (median: 37; IQR 156.2) post-orchiectomy. 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), respectively. Univariable analysis revealed LDH ≥1.5 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.

Conclusions

HCG values correlate with the tumour stage and levels ≥2.000 IU/l are associated with an impaired outcome concerning OS. Our results should be considered for the risk stratification of HCG positive seminoma patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

T. Hermanns: Advisory / Consultancy: Bayer und MSD. U. De Giorgi: Research grant / Funding (self): AstraZeneca, Roche, Sanofi; Travel / Accommodation / Expenses: BMS, Ipsen, Janssen, Pfizer; Advisory / Consultancy: Astellas, Bayer, BMS, Ipsen, Janssen, Merck, Pfizer, Sanofi. R. Cathomas: Advisory / Consultancy: AstraZeneca, Astellas, Bayer, Janssen, Sanofi, BMS, MSD, Roche, Pfizer; Speaker Bureau / Expert testimony: Debiopharm, Astellas. C. Oing: Honoraria (self), Travel / Accommodation / Expenses: IPSEN, Medac; Research grant / Funding (institution): Roche. All other authors have declared no conflicts of interest.