PIN I-III: when should we interfere?

The identification of 2 or 3 different grades of prostate intraepithelial neoplasia has led to a number of difficult concepts and treatment possibilities. Postmortem examination of the prostates of men over the age of 20, who have died of other causes, mainly road traffic accidents, have been examined and the earliest signs of intraepithelial neoplasia can be seen in some of them. The most common age for prostate cancer to present clinically is between 60 and 65 years and because the majority of men do not develop clinical prostate cancer, there must be a very large number who never progress further than PIN I or II. It is very rare for the early stages of intraepithelial neoplasia to be associated with frank carcinoma. However, it is known that PIN III is frequently found in the presence of carcinoma elsewhere in the gland and this stage is seen as a premalignant development. PIN III in the presence of prostate carcinoma is treated by whatever modality is used to treat the carcinoma. In the absence of carcinoma, there are urologists who consider that it should be regarded as a T1 tumor and radical prostatectomy or radiotherapy with delayed hormonal therapy are definite alternatives. From a certain amount of anecdotal evidence, it seems that the transition from PIN III to a focal carcinoma may take in the order of 2-3 years. Whether this transition can be definitely postponed by the early use of hormonal therapy is not known. Prostate intraepithelial neoplasia may also be treated by other modalities such as anti-angiogenesis agents, gene therapy, anti-metastatic agents, or metalloproteinase inhibitors. The effects of these treatments can be examined histologically by repeated biopsies to ensure that the process remains arrested. If the process of intraepithelial neoplasia can be identified at early stages, dietary modifications may well reduce mitogenic influences and slow down the process or even halt it altogether.