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Eleni Efstathiou and Christopher J. Logothetis

With testicular cancer, a disease with a cure rate of 95%, the challenge is to restore quality of life to pretreatment levels and sustain it long-term. Although the implementation of guidelines and optimization of treatment modalities over the past years have served this purpose, some complications remain inevitable and experts are still challenged with late complications of outdated treatment standards. This article focuses on the late complications of cisplatin-based chemotherapy without disregarding those of currently applied infradiaphragmatic radiation. The most serious long-term complications of chemotherapy or radiotherapy are cardiovascular toxicity and second malignancies, as each has a 25-year risk of approximately 16%. Compared with the general population, risk for second malignancies remains significantly increased for at least 35 years after treatment. Chemotherapy-related cardiovascular toxicity is probably a result of both direct endothelial damage induced by cisplatin and indirect hormonal and metabolic changes. The increased incidence of the metabolic syndrome identified in long-term survivors is most likely associated with the lower testosterone levels reported. Cisplatin-based chemotherapy affects not only Leydig cells but also Sertoli and germ cells, resulting in infertility in 30% to 50% of testicular cancer patients treated with chemotherapy. Chronic neurotoxicity occurs in half of men, whereas permanent ototoxicity and some degree of renal function impairment occur in up to 30%. Pulmonary fibrosis, occurring in 5% to 10% of patients treated with bleomycin, is fatal in 1%. Although current treatment of advanced disease has changed its natural course, we are challenged by an increasing incidence of late relapse, an entity with a distinct tumor biology characterized by latency and chemoresistance.