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.

FIG 1.

Overall survival for all patients (n = 232). (A) All patients. (B) All patients by International Germ Cell Cancer Collaborative Group (IGCCCG risk). (*) one patient with seminoma who did not have any markers was classified as having good risk. (C) All patients by histologic subtype. NSGCT, nonseminomatous germ cell tumor.

FIG 2.

Cumulative incidence of death by cause. (A) All patients. (B) All patients by International Germ Cell Cancer Collaborative Group (IGCCCG risk) (*) one patient with seminoma who did not have any markers was classified as having good risk. Five-year cumulative incidence of disease-related death rate: good, 6.5%; intermediate, 33.4%; poor, 56.4%; P < .001; 5-year cumulative incidence of death as a result of other causes rate: good, 1.4%; intermediate, 0%; poor, 0%; P = .93. (C) Patients with nonseminomatous germ cell tumor. (D) Patients with nonseminomatous germ cell tumor by International Germ Cell Cancer Collaborative Group (5-year cumulative incidence of disease-related death rate: good, 5.8%; intermediate, 34.0%; poor, 56.4%; P < .001; 5-year cumulative incidence of death as a result of other causes rate: good, 0%; intermediate, 0%; and poor, 0%; P = .66).

FIG 3.

Cumulative incidence of disease-related death by histology. NSGCT, nonseminomatous germ cell tumor.

FIG 4.

Cumulative incidence of disease-related death among patients with nonseminomatous germ cell tumor (NSGCT) according to type of teratoma. Ten patients with both immature and mature teratoma and one patient with teratoma with secondary somatic-type malignancy were excluded from this analysis.

FIG A1.

Chronologic changes in cumulative incidence of disease-related death (CIDD). (A) All patients. (B) The 1970s CIDD by histology. (C) The 1980s CIDD by histology. (D) The 1990s CIDD by histology. NSGCT, nonseminomatous germ cell tumors.