Intermittent endocrine therapy and its potential for chemoprevention of prostate cancer.

This chapter has reviewed the limitations of the use of chemotherapy in patients with hormone resistant prostate cancer. Although demonstrating that there is a small number of patients with very chemosensitive tumours, the age profile and intolerance to chemotherapy make it highly unlikely that this modality of treatment will be used more routinely despite the increasing evidence that the slow decline of prostate specific antigen with endocrine treatment can be used early to select patients who might respond to chemotherapy. Equally certain is that it will not be of use for chemoprevention of the early stages of this disease. Although some data suggest that tumours that respond rapidly and completely to endocrine therapy may benefit from the use of non-specific immunotherapy, there is no evidence that any form of vaccination therapy would be of value in preventing the disease in the main because all attempts to find evidence of a virus, particularly a human papillomavirus subtype, involved in its aetiology have proved negative. The discovery that standard endocrine therapy induces thymic regeneration and peripheral blood lymphocytosis, taken together with the demonstration that surgical trauma induced by a needle biopsy could accelerate tumour dissemination because of tumour activation by trauma induced release of tissue repair cytokines, has led to the proposal that short term endocrine treatment should be given to all prostate specific antigen positive patients prior to needle biopsy. New information on the slow kinetics of prostate cancer growth, with cancers detected by screening being found up to 20 years before clinical presentation and more than 80% of early tumours failing to double the prostate specific antigen level within 2 years, has led to proposals for a new strategy for endocrine chemoprevention of prostate cancer. This has in part been encouraged by greater confidence in the use of intermittent hormone therapy to treat patients with metastatic disease. These observations have led to the suggestion that it might be possible to prevent deaths by treating early cases detected from prostate specific antigen screening with short term (1-3 months) endocrine treatment every 5 to 10 years.