Impact of teratoma on the cumulative incidence of disease-related death in patients with advanced germ cell tumors

Abstract

PURPOSE In men with metastatic germ cell tumors (GCTs), risk-directed treatment is determined, in part, by a distinction between seminoma and nonseminomatous GCT (NSGCT). The importance of NSGCT cell type is uncertain. We evaluated the long-term impact of teratoma on survival in patients with NSGCT. METHODS Prechemotherapy, primary tumors from patients who received platinum-based chemotherapy were studied, and the histology was confirmed by a genitourinary pathologist. The cumulative incidence of disease-related death (CIDD) was the primary end point, and a competing-risk analysis was performed. RESULTS Tumors were available from 232 patients, including 193 with NSGCT. An element of teratoma was present in 82 NSGCT primary tumors (42%). With a median follow-up of 17 years (range, 0.3 to 35 years), 58 patients with NSGCT died, 47 as a result of GCT and 11 as a result of other causes. Most GCT deaths occurred within the first 5 years and were associated with pretreatment risk status (P, .001). Death as a result of other causes rose steadily after 15 years and was not associated with risk status (P = .66). A higher CIDD was observed in patients who had NSGCT with teratoma than those with NSGCT without teratoma and seminoma (5-year CIDD rate, 27.4%, 17.4%, and 10.3%, respectively; P = .03). A higher CIDD was observed in patients who had NSGCT with mature teratoma compared with those with either NSGCT with immature teratoma or NSGCT without teratoma (5-year CIDD rate, 38.1%, 19.9%, and 17.4%, respectively; P = .01). CONCLUSION The presence of teratoma, particularly mature teratoma, in an NSGCT primary tumor is associated with a higher CIDD, consistent with the hypothesis that differentiation is associated with adverse outcomes. Death as a result of non-GCT causes is not associated with risk status and must be separated from GCT death when evaluating long-term survival.