Chemotherapy Is of Limited Efficacy in the Control of Contralateral Testicular Intraepithelial Neoplasia in Patients with Testicular Germ Cell Cancer

Introduction: Testicular intraepithelial neoplasia (TIN, also called carcinoma in situ of the testis), the precursor of testicular germ cell tumors, will progress to invasive cancer unless appropriate treatment is instituted. Orchiectomy and local radiotherapy have been shown to eradicate TIN safely. The efficacy of chemotherapy is equivocal to date. Patients and Methods: Eleven patients with unilateral testicular cancer (5 pure seminoma, 6 nonseminoma) and biopsy-proven contralateral TIN underwent chemotherapy. Four patients received 2 courses of carboplatin single agent, 4 had 2 courses of platin, etoposide, bleomycin (PEB) treatment and 3 had a full 3-cycle treatment with PEB. Rebiopsy to look for persistent TIN was performed after a mean interval of 8.8 months (range 2-31). The patients were then followed clinically. Results: Five patients had persistent TIN upon rebiopsy. Each of the patients failing to chemotherapy had undergone 2 or 3 cycles of the PEB regimen, while 3 had received carboplatin treatment. Two of the patients with no TIN upon rebiopsy developed invasive testis cancer subsequently. In summary, 7 of 11 patients thus failed to chemotherapy (64%; exact 95% confidence interval 30.8-89.1%). Three of the patients had complete absence of spermatogenesis upon rebiopsy histologically, while the remaining cases showed various forms of spermatogenetic arrest. Three of the failing patients were rescued by local radiotherapy, 4 patients underwent partial orchidectomy followed by local radiotherapy. No relapse occurred thereafter. Conclusions: Chemotherapy was shown to be of only little effect in eradicating TIN. The failure rate of 64% is much higher than reported previously. As the majority of failing cases had received carboplatin single-agent therapy or adjuvant PEB therapy with 2 cycles, it may be speculated that the efficacy of chemotherapy regarding TIN clearance is dose dependent. Multidrug regimens appear to be more efficacious than single-agent therapy. As spermatogenesis is only incompletely eliminated by chemotherapy, it is postulated that chemotherapy does no more than temporarily suppress TIN, while only selected cases are cleared of the lesion. Practically, rebiopsy to look for retained TIN about 2 years after completion of chemotherapy is valuable. Copyright (C) 2009 S. Karger AG, Basel