Therapy-related malignancies following treatment of germ cell cancer.

Given the young age at which testicular cancer is treated and the excellent prognosis for patients suffering from this disease, therapy-related malignancies represent a significant problem. Therapy-related solid tumors are associated mainly with the use of radiation therapy. The risk for developing a therapy-related solid tumor is approximately 2- to 3-fold increased compared with the general population. Therapy-related leukemias are associated predominantly with chemotherapy, particularly with the use of topoisomerase-II inhibitors and alkylating agents. In general, the cumulative incidence of therapy-related leukemia is low. It is approximately 0.5% and 2% at 5 years of median follow-up for patients receiving etoposide at cumulative doses < or = 2 g/m2 and > 2 g/m2, respectively. High cumulative doses of etoposide given over a short period of time appear to be less leukemogenic than a similar dose of etoposide given over a longer period of time. There might, additionally, be a synergistic effect of cisplatin and etoposide on the induction of therapy-related leukemia. For patients who receive high-dose chemotherapy with autologous stem-cell support, the risk of therapy-related myelodysplastic syndrome and leukemia appears to be substantially lower compared with that reported in non-Hodgkin's lymphoma patients undergoing high-dose chemotherapy. The transplantation procedure itself does not appear to add to the therapy-related leukemia risk. The risk-benefit analysis in patients with testicular cancer clearly favors the use of current treatment regimens including high-dose chemotherapy. However, even the acceptably low number of therapy-related leukemias should encourage the search for equally effective but less toxic therapies.