Prospective phase I study on testicular castration induced by radiation treatment

Surgery and luteinizing hormone-releasing hormone (LHRH) analogs are standard androgen deprivation treatments (ADT) for patients with advanced prostate cancer. We performed a phase I study to explore if irradiation to the testes could be used as an alternative to ADT.

All patients had advanced prostate cancer with normal testosterone levels before treatment and indication for long term castration. Treatment started with one LHRH analog injection (to induce a fast drop of testosterone) followed by irradiation to the whole scrotum. Two fractionation regimens were tested: 17 Gy in 2 fractions, and 24 Gy in 3 fractions. Hormonal blood evaluation was performed before and every 3 months after radiotherapy. Toxicity was evaluated at each visit by the CTCv3 scoring system. This was an IRB approved prospective study.

The first three patients received 17 Gy in 2 fractions. None of them developed acute or late skin toxicity and none became castrated, keeping normal levels of testosterone during the time they were followed at 11, 24 and 36 months post-radiotherapy. Another four patients received 24 Gy in 3 fractions. Two developed grade 1 temporary acute dermatitis and, again, none of them became castrated during follow up of 11-36 months.

Prospective studies assessing the effect of the Leydig cells after direct irradiation to the testes are rare. The two radiotherapy regimens used in this study were well tolerated, but not capable of causing castration after 11-36 months of follow up. It is not yet clear whether radiation treatment can effectively induce castration in men.