Late toxicity after treatment for testicular germ cell cancer

Improved survival in testicular cancer has been accompanied by concern abou t longterm side effects of chemotherapy or radiotherapy. Secondary malignan t neoplasia represents one of the worst possible longterm complications, le ading to death in patients cured of their primary malignancy. Patients with testicular germ cell tumors appear to have a 2-fold increased risk of deve loping any second cancer 25-30 years after the diagnosis, resulting in a cu mulative incidence of 16-23% at that time. The risk for secondary solid tum ors can be mainly attributed to radiotherapy. There is strong evidence of a n increasing risk for secondary solid tumors with time since treatment. Tum or-specific analysis of the risk for second cancers revealed statistically significant excesses for stomach, pancreas, bladder, rectum, prostate, and kidney cancer, as well as for cancer of the thyroid, melanoma, sarcomas, an d non-Hodgkin's lymphoma. No significantly elevated risk for secondary soli d tumors was observed after treatment with chemotherapy alone. The risk of secondary leukemia was associated with both radiotherapy and in particular with chemotherapy. In recent clinical surveys of patients with testicular cancer, estimates of the risk of leukemia after chemotherapy hav e ranged from 70- to 300-fold. An elevated risk was observed within the fir st two decades after diagnosis, later the risk was as expected in the norma l population. Etoposide seems to be leukemogenic, especially at cumulative doses higher than 2 g/m(2), although the effects of dose and schedule as we ll as the effects of other cytotoxic agents and radiotherapy remain to be f inally clarified. Based on currently available data in patients with testic ular cancer, it can be concluded that a significant elevated risk for the d evelopment of secondary leukemia exits after chemotherapy. However this ris k does by far not outweigh the therapeutic benefit of etoposid-based therap y in patients with germ cell tumors. Secondary Raynaud's phenomenon is the main late vascular toxicity affecting about one third of patients after curative chemotherapy for testicular can cer. Hypertension will occur in one fifths of the patients. The incidence o f Vascular toxicity appears to be lower following FEB-therapy compared to P VB-therapy and major vascular events seem to be rare. Other frequent sympto matic toxicities are ototoxicity and peripheral neuropathy. A major risk fa ctor for the development-of toxicity is the cumulative dose of cisplatin gi ven. Alterations of gonadotropin levels and Leydig cell insufficiency persi st in more than half of young patients cured from testicular cancer by cisp latin-based combination chemotherapy. Approximately one fourth of patients have low serum magnesium or phosphat levels, or elevated creatinine levels. These toxicities seldomly result in clinical symptoms. We conclude that 3- 4 courses with bleomycin, cisplatin and etoposide in testicular cancer pati ents will only rarely lead to symptomatic impairment of organ functions and a decrease of quality of life. Germ cell cancers have served as a valuable model for the development of ne w treatment strategies contributing largely to defining the role of cisplat inum, etoposide and recently ifosfamide in medical oncology. However, germ cell cancer may also be a useful model for investigating the long term side effects of the oncological therapies. Thus, germ cell cancer is not only a "model for a curable neoplasm" (L.H. Einhorn) but can also be seen as a "m odel for the study of late sequelae of modern oncological therapies."