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Definition |
Long-term castration stimulates prostate cell apoptosis. After an average period of 24 months, the tumour relapses, characterised by a castrate-independent state of growth. Experimental data indicate that castrateindependent progression may begin early after castration, coinciding with the cessation of androgen-induced differentiation of stem cells. It has been suggested that stopping castration prior to progression would mean that any subsequent tumour growth would be solely sustained by the proliferation of androgendependent stem cells. The stem cells should therefore be susceptible once again to androgen withdrawal. Thus, IAD could delay the emergence of the androgen-independent clone. This rationale has been developed mainly through models (e.g. the Shionoggi breast model), which may be significantly different to tumour behaviour in men. Other possible benefits of IAD include the preservation of QoL in off-treatment periods and a reduction in treatment cost. IAD is feasible and accepted by patients. Two independent reviews summarised the clinical efficacy of this attitude. They were based on seven RCTs. Of the seven trials, only three trials were in patients with M1 disease. The three remaining trials were combinations of different relapse situations, mainly locally advanced and metastatic cases. The design of the seven trials is summarised in Table 6.6.1, while the main results for survival are summarised in Table 6.6.2. The most important survival finding was the lack of a significant difference in OS between continuous and intermittent ADT. Table 6.6.3 summarises the expected treatment benefits of IAD. The most important finding was that the benefit in overall QoL was at best minimal if any. However, some treatment side effects were decreased using IAD.
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