After radiotherapy testosterone stimulation is unable to increase growth in the dunning R3327-PAP prostate tumour

A study was carried out to investigate whether testosterone treatment is able to influence tumour growth in a rat prostatic adenocarcinoma previously treated with castration and high-dose fractionated irradiation. Copenhagen x Fisher rats bearing the androgen-sensitive, well-differentiated Dunning R3327-PAP tumour were castrated and thereafter treated with external beam radiation with photons from a 4-MV linear accelerator. One month after irradiation, substitution with subcutaneous testosterone was started. Tumour volumes and rat weights were monitored up to 256 days after castration, and at the end of the study a microscopic analysis of the tumours was performed. Irradiation delayed tumour growth as compared with untreated tumours. Castration delayed tumour growth, but a hormone-refractory relapse to doubled tumour volume was seen within 45 days. If testosterone was added after castration, the tumours grew rapidly. However, testosterone failed to increase tumour growth when given to rats treated with orchiectomy and irradiation. Histological examination showed that the irradiated tumours still contained tumour epithelial cells, but these cells apparently do not respond to testosterone stimulation. The well-differentiated and androgen-sensitive rat prostatic adenocarcinoma did not grow after irradiation despite stimulation with testosterone. This indicates that the malignant cells lose their androgen sensitivity after high-dose irradiation.