The relative risk of second nongerminal malignancies in patients with extragonadal germ cell tumors

BAGKGROUND, Apart from a recognized association between extragonadal medias tinal germ cell tumors (GCT) and the occurrence of hematologic malignancies , the risk of developing second nongerminal solid tumors after the diagnosi s or treatment of eztragonadal GCT is unknown. METHODS. Siz hundred thirty-five consecutive patients with extragonadal GCT treated at 11 centers in the U.S. and Europe during the era of cisplatin-b ased chemoteherapy (1975-1996) were included into a large database. These p atients were evaluated for the occurrence of second malignancies. RESULTS. No treatment-related leukemia was observed in 611 patients treated with chemotherapy. In 7 patients, second solid tumors were observed, resul ting in a frequency of 1.86% (95% confidence interval [95% I], 1.79-1.93%) after a median follow-up of 55 months (95% CI, 50-60 months) (annual incide nce, 0.30% [95% CI, 0.14-0.59]). Four solid tumors (57%) developed in patie nts with primary mediastinal and 3 tumors (43%) developed in patients with retroperitoneal GCT. Three patients (43%) had a nonseminomatous and 4 patie nts (57%) had a seminomatous histology. Six patients had been treated with chemotherapy and one patient with radiotherapy. Six of 7 solid tumors (86%) had developed within 5 years and 7 of 7 solid tumors within 10 years of di agnosis. The median time period to the occurrence of neoplasia was 47 month s (range, 9-145 months). Four cutaneous tumors were observed (melanoma, two patients; basal cell carcinoma, one patient; and squamous cell carcinoma, one patient); the other three tumors were angiosarcoma, nonsmall cell lung carcinoma, and colorectal carcinoma. The overall risk for developing a seco nd tumor was not increased compared with an age-matched general population with a standard incidence ratio (SIR) of 1.49 (95% CI, 0.60-3.06). An eleva ted risk for skin tumors was observed in all extragonadal GCT patients (SIR , 4.00 [95% CI, 1.09-10.24]), as well as in the subgroup of patients treate d with chemotherapy (SIR, 5.33 [95%, CI, 1.45-13.65]). CONCLUSIONS, This analysis excludes an increased biologic risk of developin g second solid malignancies in patients with extragonadal GCT except for th e previously reported association between primary mediastinal nonseminoma a nd hematologic disorders. The overall risk of developing second malignancie s in extragonadal GCT patients appears to be comparable to that in patients with primary testicular carcinoma. The incremental occurrence of skin mali gnancies in patients treated with chemotherapy should be investigated furth er. (C) 2000 American Cancer Society.