GC provides a similar survival advantage to MVAC with a better safety profile and tolerability. This better-risk benefit ratio should change the standard of care for patients with locally advanced and metastatic TCC from MVAC to GC.

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Not only spermatogenesis but also Leydig cell function is impaired in testes with CIS. This impairment could be due to common factors in the pathogenesis of germ cell neoplasm and testicular dysfunction. Alternatively, CIS cells may have a negative impact on Leydig cell function.

Thirty patients treated for germ cell cancer with six cycles of cisplatin, vinblastine, and bleomycin participated in a follow-up examination of neurotoxicity 49 to 106 months after treatment. Of these, 22 patients (73%) had sensory loss; half of them complained of paresthesias. The vibration perception threshold was increased in 24 patients (80%). Auditory stimulation revealed a normal latency of the first component of the brain stem-evoked potentials Pl but an increased interpeak interval between this and Pv; reflecting a central conduction defect. Motor conduction velocity (CV) along the peroneal nerve was normal. The average sural nerve CV was decreased (P less than .01) and the sensory action potential amplitude was reduced (P less than .01). Warm perception threshold was increased in 10 patients (33%). Cortical-evoked potentials after tibial nerve stimulation had increased latencies in 29 patients (97%). The peripheral CV along the tibial nerve was slowed (P less than .01) in 19 patients, and the central conduction time from Th12 to cortex was prolonged in 15 patients (P less than .01). The changes in conduction along peripheral and central pathways after tibial nerve stimulation are compatible with a toxic effect on the sensory root ganglia causing a "dying back" axonal degeneration of central and peripheral nerve fibers.

Testicular irradiation is a safe treatment at dose level 20 Gy (10 x 2 Gy). Decrease of dose to 14 Gy (7 x 2 Gy) might lead to risk of relapse of CIS. Impairment of hormone production without clinically significant dose dependency is seen in the dose range 14 to 20 Gy.

Fertility and Leydig cell function were investigated in 31 patients previously treated for nonseminomatous testicular cancer. Twenty-two patients with metastatic cancer had received cisplatin-based chemotherapy, and the median follow-up was 64 months (range, 42 to 100 months). Nine patients without metastases were treated with orchiectomy alone, and follow-up in this group was a median of 61 months (range, 40 to 77 months). None of the patients have relapsed and retroperitoneal lymph node dissection was not performed in any patient. Both the concentration of spermatozoa and the volume of the remaining testis are significantly reduced in patients who had previously received chemotherapy when compared with patients treated with orchiectomy alone (P less than .05). There were no significant differences between groups when comparing morphology, motility, and penetration of the spermatozoa. Subclinical Leydig cell dysfunction with normal testosterone and elevated luteinizing hormone (LH) was observed in one patient (11%) treated with orchiectomy alone, while 59% of the patients who had received chemotherapy had elevated LH (P less than .05). We conclude that cisplatin-based chemotherapy leads to a persistent impairment of fertility and Leydig cell function in the majority of patients with testicular cancer.

Testicular irradiation is a safe treatment at dose level 20 Gy (10 x 2 Gy). Decrease of dose to 14 Gy (7 x 2 Gy) might lead to risk of relapse of CIS. Impairment of hormone production without clinically significant dose dependency is seen in the dose range 14 to 20 Gy.