ABSTRACT: BACKGROUND:Using a large, nationally representative, population-based cancer registry, this study systematically evaluated the impact of the location and burden of extranodal testicular germ cell tumor (TGCT) metastases on survival. METHODS:Men with stage III TGCTs captured by the Surveillance, Epidemiology, and End Results registry from 2010 to 2015 with distant extranodal metastases were identified. Clinicopathologic information was collected, and patients were subdivided according to the specific organ site or sites of metastatic involvement (lung, liver, bone, and/or brain). Kaplan-Meier analysis and multivariable Cox regression were used to evaluate cancer-specific survival (CSS), and model performance was assessed with Harrell's C statistic. RESULTS:Nine hundred sixty-nine patients with stage III TGCTs were included with predominantly nonseminomatous histology (84%). Most patients (91%) had pulmonary metastases, whereas 20%, 10%, and 10% had liver, bone, and brain metastases, respectively. Over a median follow-up of 21 months, 19% of these men died of TGCTs. When they were grouped by the primary site of metastasis, patients with more than 1 extrapulmonary metastasis exhibited the worst CSS (hazard ratio [HR] vs isolated pulmonary involvement, 4.27; 95% confidence interval [CI], 2.60-7.00; P < .01). Among patients with isolated extrapulmonary involvement, those with brain metastases had the poorest survival (HR, 3.24; 95% CI, 1.98-5.28; P < .01), and they were followed by patients with liver (HR, 2.29; 95% CI, 1.56-3.35; P < .01) and bone metastases (HR, 1.97; 95% CI, 1.11-3.50; P = .02). Harrell's C statistic (multivariable) was 0.71. CONCLUSIONS:The site of metastatic involvement affects survival outcomes for patients with TGCTs, and this may reflect both the aggressive biology and the challenging treatment of these tumors. Further incorporation of organotropism into current prognostic models for metastatic TGCTs warrants attention.
