Low-grade, latent prostate cancer volume: Predictor of clinical cancer incidence?

We hypothesize that each cell in lowgrade (Gleason grade 1-3) prostate cancer tissue is at risk of transformation into a cell which produces a highgrade (Gleason grade 4-5) clinical cancer after a short period of growth. As a consequence, the volume of low-grade, latent cancer tissue in the prostate glands of men at any age determines their incidence rate for high-grade, clinical cancer a few years later. Autopsy and incidence data for both white men and black men support this conclusion, with a tumor growth period of about 7 years. The transformation rate is similar for black men and for white men, about 0.024 high-grade cancers per year per cm³ of lowgrade latent cancer volume. Our hypothesis explains the infrequent occurrence of clinical cancer despite the high prevalence of latent cancer, the steep rise of clinical cancer incidence with age despite the slow rise of latent cancer prevalence with age, and the disparities in clinical cancer incidence among some populations despite their similar latent cancer prevalence. This hypothesis suggests that low-grade cancer volume is a critical determinant of clinical cancer risk. [J Natl Cancer Inst 83:1231-1235, 1991]