GONADAL-FUNCTION OF PATIENTS TREATED WITH CISPLATIN-BASED CHEMOTHERAPY FOR GERM-CELL CANCER

Purpose: The cure rate of patients with germ cell cancer of the testis has considerably improved since the introduction of cisplatin based c hemotherapy. Because these patients are in their reproductive years an d because some of them will be infertile after treatment, the effects of cytotoxic treatment-on gonadal function are investigated by hormona l evaluations. Materials and Methods: In a transversal trial, luteiniz ing hormone, follicle-stimulating hormone and testosterone were determ ined radioimmunologically in serum samples of 232 patients with germ c ell tumors after unilateral orchiectomy (patient age 18 to 64 years) u p to 153 months after chemotherapy. Additionally, 51 of these patients were investigated in a longitudinal trial before and up to 5 years af ter chemotherapy. All patients received at least 2 courses of differen t cisplatin based chemotherapy regimens: cisplatin/vinblastine/bleomyc in, cisplatin/vinblastine/bleomycin/ifosfamide, cisplatin/etoposide/bl eomycin, platin/vinblastine/bleomycin/ifosfamide/etoposide. Additional ly, 11 patients with germ cell tumors (age 22 to 38 years, stage I) we re investigated within the first year after orchiectomy and retroperit oneal lymphadenectomy but without chemotherapy. Results: In the transv ersal trial, 24 of 73 patients investigated during the first year afte r chemotherapy showed elevated luteinizing hormone concentrations, 5 h ad subnormal serum testosterone and 65 had elevated serum follicle-sti mulating hormone, reflecting spermatogenesis deficits. In 28 patients studied longer than 8 years after chemotherapy (median followup 8.5 ye ars, range 8.0 to 12.6), luteinizing hormone was elevated in 1 patient , follicle-stimulating hormone was increased in 18 and testosterone wa s subnormal in 1. Patients without chemotherapy treatment showed gonad otropin and testosterone within normal range and 3 patients had elevat ed serum follicle-stimulating hormone. In the longitudinal study, mean serum luteinizing hormone plus or minus standard deviation (3.45 +/- 0.05 IU/l.), follicle-stimulating hormone (7.79 +/- 0.13 IU/l.) and te stosterone (18.6 +/- 0.17 nmol./l.) were within the normal range befor e chemotherapy; serum follicle-stimulating hormone increased after che motherapy and 60 months after treatment, and follicle-stimulating horm one was still significantly elevated (16.9 +/- 0.71 IU/l., 19 cases, p < 0.001). Mean luteinizing hormone and testosterone levels were withi n the normal range, but 60 months after therapy the testosterone-to-lu teinizing hormone ratio was still lower than before treatment (p < 0.0 5). Conclusions: In patients with germ cell tumors, a compensated insu fficiency of the function of the Leydig cells was still observed up to 60 months after chemotherapy. Of these patients 68% showed elevated f ollicle-stimulating hormone levels, which reflected a functional insuf ficiency of the Sertoli cells with impaired spermatogenesis. This stud y shows that impairment of germinative functions is more severe and pr otracted than the impairment of the endocrine functions.