Effect of time of castration and tumour volume on time to androgen‐independent recurrence in Shionogi tumours

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Abstract
The understanding of the timing and development of the recurrence of androgen‐independent prostate cancer is limited and has significant clinical implications. The paper by So et al. addresses, for the first time, the concept of recurrence after androgen ablation in an animal model. They show clearly in this well designed and conducted study that the recurrence of an androgen‐independent cancer depends on both the initial size of the tumour and the delay leading to castration. These results have significant clinical importance in the understanding and treatment of prostate cancer.OBJECTIVE: To use the androgen‐dependent Shionogi tumour model in mice to help define the effects of the timing of androgen ablation on the development of androgen resistance in prostate cancer, as the timing of androgen ablation remains controversial.MATERIALS AND METHODS: Groups of nine mice were castrated at 1, 3, 6, 10 and 14 days after tumour inoculation, with a similar‐sized group of mice castrated before tumour inoculation serving as a control. The time of first palpable tumour recurrence and tumour volume was monitored after castration.RESULTS: All mice were observed for ≥ 80 days after castration. Only mice castrated at 10 and 14 days had palpable tumour at the time of castration. Mice castrated at 14 days had the highest rate of early tumour recurrence (all nine) while mice castrated before inoculation or at 1 and 3 days afterward had a significantly lower rate of tumour recurrence (four of nine; P < 0.01). Mice castrated at 14 and 10 days had tumour recurrence significantly earlier than mice in the other groups. When calcium‐channel blockers were administered to inhibit apoptosis, all mice had a similar time to recurrence and time to death regardless of the time of castration.CONCLUSIONS: Large tumour volume and corresponding delay in castration reduced the time to androgen‐independent tumour recurrence and survival. Earlier androgen ablation, at the time of subclinical (impalpable) disease, significantly delayed the rate and time to androgen‐independent recurrence compared with delayed therapy when the tumour burden was high.

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