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 analyzed. 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 nonseminoma in 77% and seminoma in 23% of patients.After a median follow-up of 18 months (range, 0-228), estimated median PFS and OS were 21 (range, 0-225) and 98 months ((95%)CI, 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; (95%)CI, 1.05-3.50; OS; HR 2.16; (95%)CI, 1.14-4.09) and the presence of liver and/or brain metastases (PFS; HR 1.89; (95%)CI, 1.13-3.17; OS; HR 1.91; (95%)CI, 0.024) Seminomatous histology was the strongest predictor for favorable PFS (multivariate cox regression; HR, 0.32; p=.011) with respective 2-year PFS and OS rates of 68% and 75% compared to 24% and 36% for nonseminoma patients.

CONCLUSIONS: Outcome of GCT patients with primary metastatic bone disease is particularly poor in nonseminoma 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.