Purpose: Second malignancies in patients with pure testicular seminoma were studied in order to look for adverse late effects of treatment and to study the significance of second malignancies during follow-up. Patients, Methods: In a multicentric investigation, 839 consecutive patients with pure testicular seminoma were observed for a median follow-up of 3.9 years. Thirty-seven patients had been excluded from the study because they already had had either a contralateral testicular germ cell tumor or another malignancy. 758 patients received radiotherapy, 76 underwent chemotherapy, 5 had surveillance only. The expected rate of second cancers was calculated according to the data of the cancer registry of Saarland, Germany. Results: Twenty-two second cancers (13 contralateral testicular tumors, 9 extratesticular malignancies) were recorded. The overall risk of having a second cancer was RR = 4.8 (95% CI 3.0–7.3). The risk of having a subsequent testicular tumor is RR = 44.8 (95% Cl 23.9–76.7). 1.1% of the patients developed a nontesticular second tumor. The risk of having a nontesticular second cancer is RR = 2.1 (95% CI 1.0–4.0). A significantly increased risk was observed for renal cell cancer as well (RR = 12.5; 95% Cl: 1.5–45.1). Increased RR without reaching statistical significance were found for rectal cancer (RR = 5.0; 95% Cl: 0.1–27.9) and non-Hodgkin lymphoma (RR = 6.7; 95% CI 0.2–37.1). None of the second cancers were directly located within the radiation field; 5 neoplasms arose at the border of the radiation field. Conclusions: This study confirmed the increased risk of having a second testicular germ cell cancer. There is also a small but definitely increased overall risk of having a nontesticular second cancer. Treatment-unrelated factors – possibly genetic predisposition – must be considered for a substantial number of these second tumors, since in the present study the follow-up was rather short and most of the second cancers were located outside of the radiation fields. In particular, the association of renal cancer with testicular cancer appears to be a more than chance occurrence. Second cancer is a real hazard following treatment of testicular cancers and should always be considered during follow-up.

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