Long-term mortality in patients with germ cell tumors: Effect of primary cancer site on cause of death

Objectives: To examine the effect of extragonadal tumor site on the risk for cardiovascular, hematopoietic malignancies, and solid cancer-related causes of death. Patients and methods: Male patients diagnosed with germ cell tumors (GCTs) between 1973 and 2008 were identified from the Surveillance, Epidemiology and End Results database, and stratified by the site of primary cancer (mediastinal and nonmediastinal extragonadal vs. gonadal). Using competing risk analysis restricted to events that happened at least 5 years after diagnosis, we examined the possible effect of primary tumor site on the risk for death related to hematopoietic malignancies, cardiovascular disorders, and solid cancers in the study cohort. Results: Of 37,283 patients included in our analysis, 17,715 were diagnosed with nonseminomas and 19,568 with seminomas. Eight hundred and twenty four patients (2%) were diagnosed with primary mediastinal GCTs and 1,469 (4%) with nonmediastinal extragonadal tumors. Patients with mediastinal GCTs had an increased risk for death related to hematopoietic malignancies (hazard ratio [HR] = 8.84; 95% confidence interval [CI]: 3.16-24; P<0.0001) and cardiovascular disorders (HR = 4.45; 95% CI: 2.52-8.0; P<0.0001), but no significant difference in risk of dying of solid cancers (HR = 1.46; 95% CI: 0.36-5.9; P = 0.59) compared to patients with gonadal GCTs. Patients with nonmediastinal extragonadal GCTs had a significantly increased risk for dying of cardiovascular disorders (HR = 2.75; 95% CI: 1.67-4.51; P<0.0001), but not a significantly different risk for dying of hematopoietic malignancies (HR = 0.93; 95% CI: 0.13-6.84; P = 0.94) or solid cancers (HR = 1.45; 95% CI: 0.68-5.0; P = 0.23) compared with patients with gonadal GCTs. Conclusions: Patients with GCTs and extragonadal primary sites have an increased risk for death from cardiovascular disease and hematopoietic malignancies compared to those with gonadal GCTs, and could benefit from more intense preventive measures to decrease the risk of death related to these disorders.