Impact of primary metastatic bone disease in germ cell tumors: results of an International Global Germ Cell Tumor Collaborative Group G3 Registry Study

Background: Bone metastases (BM) are rare in germ cell tumor (GCT) patients. Systematic data on risk factors, treatment and outcome are largely lacking. Patients and methods: A database created by an international consortium including 123 GCT patients with BM at primary diagnosis was retrospectively analysed. Survival estimates were calculated by the method of Kaplan-Meier and compared by log-rank testing. Cox regression analysis was applied for risk factor analyses. Results: In our cohort of patients, BM at primary diagnosis more often affected multiple sites (61%) and BM as the only metastatic site were scarce (9%). Histology was non-seminoma in 77% and seminoma in 23% of patients. After a median followup of 18 months (range, 0-228), estimated median PFS and OS were 21 (range, 0-225) and 98 months ((CI)-C-95%, 36-160), respective 2-year PFS and OS rates were 34% and 45%. Negative prognosticators in univariate analysis were a mediastinal primary (PFS; HR 1.92; (CI)-C-95%, 1.05-3.50; OS; HR 2.16; (CI)-C-95%, 1.14-4.09) and the presence of liver and/ or brain metastases (PFS; HR 1.89; (CI)-C-95%, 1.133.17; OS; HR 1.91; (CI)-C-95%, 0.024) Seminomatous histology was the strongest predictor for favorable PFS (multivariate Cox regression; HR, 0.32; P = 0.011) with respective 2-year PFS and OS rates of 68% and 75% compared with 24% and 36% for nonseminoma patients. Conclusions: Outcome of GCT patients with primary metastatic bone disease is particularly poor in non-seminoma patients, even worse than the expected outcomes of the general IGCCCG 'poor prognosis' group. This series does not indicate that mutlimodal treatment improves the prognosis over stage-adapted chemotherapy alone, however, the statistical power of these results is limited due to low patient numbers in each specific subgroup.