Overdiagnosis of occult prostate cancer in aging men causes needless morbidity. A decade of intensive effort to increase the early detection of prostate cancer has led to increasing reliance on PSA, the development of new forms of PSA measurement such as Free PSA and Complexed PSA, and lowering of the """"""""normal"""""""" threshold values resulting in increased biopsy rates. Biopsy protocols are also becoming increasingly invasive, with a trend from six systematic biopsies to 12, 18 and beyond. This has resulted in a huge increase in the number of prostate cancers diagnosed, indeed, with many more cancers diagnosed in the localized stages and a marked decrease in advanced or metastatic disease at diagnosis. Whether the concurrent drop in prostate cancer mortality is due to more aggressive early detection is still being evaluated. The worldwide incidence of prostate cancer diagnosed according to age, racial group and geographic distribution is becoming well understood. However, the true prevalence of prostate cancer is not well known, which hinders effective targeting of early detection efforts. Recent autopsy studies suggest that small, well to moderately differentiated prostate cancers are present in American males as early as in their 20's, and increase with each decade to 65 to 70% of 60-69 year olds and 81 to 83% of 70-79 year olds, regardless of race. Low-grade tumors of less than 0.5 cc are generally considered to be biologically unimportant and most such occult tumors do not progress to clinical significance. The clear and present danger is that in the aging male, where these occult tumors are most common and numerous, increasingly sensitive PSA tests and more biopsies will lead to the diagnosis of many clinically insignificant cancers that should not be treated. In the absence of benefit, the aging population will incur only the morbidity of the diagnosis and unnecessary treatment. The relationship between increasingly sensitive PSA, more extensive biopsy regimens and the detection of smaller occult carcinomas is not known. Prostate glands from fresh cadavers will be step sectioned, whole mounted and mapped for the presence of cancer, the number of loci, volume, grade, location and associated benign conditions. The hypothesis of Aim 1 is that increasing the number of biopsies from 6 to 18 will disproportionately increase detection of clinically insignificant prostate cancers in elderly males. For directing future biopsy strategies, we will establish the relationship of the volume and location of tumors.
In Aim 2, we will determine the serum levels of tumor markers (total, free and complexed PSA, hK2, and the ratios of free/total PSA and complexed/free PSA) which correspond to the occult tumors detected in the deceased elderly men.
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