Clinical evidence for and implications of the multistep development of prostate cancer.

Based upon a large body of experimental and clinical data, it is evident that multiple malignant events are necessary for a normal cell to give rise to a fully malignant cancer cell. A critical issue with regard to human prostatic carcinogenesis is the clinical significance of the large number of cancers that are present histologically in the elderly male prostate gland. A possibility is that these histological prostate cancers already have undergone all of the malignant events necessary to produce clinically manifest cancer and, thus, only further tumor growth is required to produce a clinical tumor. Alternatively, these histological cancers may have undergone some but not all of the events necessary to produce clinical disease and, therefore, despite host longevity the cancer will remain clinically silent as long as no further malignant changes occur. This issue has importance clinically with respect to the diagnosis, therapy and possible prevention of prostatic cancer. Clinical observations and the mathematical relationship between prostate cancer prevalence and host age (time) support the fact that, in addition to growth, histological prostate cancer requires further malignant events to produce clinical disease. A better understanding of the events involved in prostate cancer development will be necessary to have a greater impact on this disease in the future.