Purpose: Secondary neoplasia represents one of the worst possible long-term complications of therapy for testicular cancer, frequently leading to death in patients cured of the primary malignancy. The frequency and importance of secondary malignant disease will be reviewed.
Methods: The international literature was screened for reports concerning secondary solid cancers or leukemias in patients treated with chemotherapy or radiotherapy for malignant germ cell tumors.
Results: Patients with testicular germ cell tumors appear to have a twofold significantly increased risk (range, 0.7 to 3.4) for the development of secondary neoplasia. Apart from contralateral testicular cancers, which are not treatment-related, a largely elevated inherited risk for secondary cancers in patients with germ cell tumors seems unlikely. Radiotherapy is associated with a two- to threefold increased risk for secondary solid tumors (range, 1.3 to 7.5). A three- to sevenfold increased risk seems to exist for the development of solid tumors arising in the previous irradiation ports, such as stomach, pancreatic, bladder, and renal cell cancer, and sarcomas. To date, no significantly elevated risk for secondary solid tumors was observed after chemotherapy, even including regimens with alkylating agents, eg, cisplatin and ifosfamide. However, the risk associated with chemotherapy needs to be reexamined when the median follow-up of studies will exceed more than 10 years. An increased relative risk for secondary leukemias after chemotherapy (range, 1.3 to 3.4) has been reported in three of eight studies with more than 300 patients. Four large studies indicate a significantly elevated risk (range, 15 to 25) for the use of conventional-dose etoposide (< 2 g/m2 cumulative dose); however, with a 5-year cumulative incidence of less than 0.5% of all patients, this risk seems small. Concerning high-dose etoposide regimens (> 2 g/m2), further studies are necessary.
Conclusion: Treatment for testicular cancer is associated with a small, but clearly identifiable, risk for secondary solid tumors that can be attributed to radiotherapy, and for secondary leukemia mainly associated with the use of chemotherapy. The frequency of secondary neoplasia observed is rather low, and in the light of the high cure rate, the risk for the individual patient appears negligible and should not alter current treatment strategies for metastatic testicular cancer.