Intermediate biomarkers for chemoprevention of prostate cancer

Use of high-grade prostatic intraepithelial neoplasia (PIN) as an intermediate biomarker for prostate cancer requires additional data concerning its natural biological behaviour. Moreover, it should be recognized that a proportion of PIN lesions may represent intraductal spread of an accompanying prostate cancer rather than a precancerous lesion. The detection rate of isolated PIN in the general population is low, and its clinical significance in the short term may be limited. Additional long-term studies on the significance of isolated PIN detected during population screening are required. Due to inadequate tissue sampling by current biopsy procedures, the presence of an accompanying prostate cancer is difficult to rule out. Endocrine therapy changes the morphology of PIN, hampering its identification by making it more closely resemble the normal benign glands. In addition, endocrine therapy may lead to molecular changes in PIN, with a potential risk of induction of resistance to endocrine therapy. Prolonged androgen deprivation (for six months) does not generally lead to eradication of PIN. Cessation of endocrine therapy is likely to lead to renewed expansion of PIN, since PIN continues to express androgen receptors and the cell-cycle protein MIB-1 under conditions of low androgen levels. Recent findings indicate that most high-grade prostate cancers seem to develop from low-grade cancers. The development of a high-grade focus of prostate cancer within a clinically latent low-grade tumour might be a suitable target for future intervention studies, provided that appropriate monitoring for development of high-grade cancer can be achieved in individual patients.