Prostate cancer may also arise in areas of the prostate that are not accessible to the examiner’s finger. This limitation may account for the difference that may occur between clinical and pathological staging. When they are indicated, imaging studies may provide further information to determine the extent of disease. Bone scan, pelvic CAT scan or MRI may increase the original clinical stage that was determined only by digital rectal examination.

Pathological staging, on the other hand, indicates the extent of cancer that is found in the surgically removed tissue specimens.  Pathological staging requires surgery so the pathologist can evaluate the removed prostate to directly assess the extent of cancer spread. Pelvic lymph nodes are also regularly removed during surgery and then assessed for cancer spread.

A review of the various ways that PSA testing aids the clinical evaluation of prostate cancer is helpful. The PSA level itself is helpful, and it is quite readily understood that the higher the number the greater the extent of disease and worse prognosis.  But,  there are exceptions.  Tumors that are poorly differentiated (extremely different from normal biological tissue) may not produce significant amounts of PSA such that the measurement in blood may seem surprisingly low. On the other hand, there are cases in which a more elevated PSA measurement can occur with a large amount of cancerous tissue present within the prostate in locations that may not easily be appreciated on the digital rectal examination, such as the anterior zone (opposite to the peripheral zone).

A complicating issue is that the PSA test is not cancer specific. The test is only prostate specific, and elevations may arise from benign diseases of the prostate such as benign prostatic enlargement and prostatitis. Other forms of PSA measurement have been developed in an attempt to correct for elevations associated with benign conditions of the prostate. These include PSA density, free PSA, and PSA velocity. These are briefly explained as follows. PSA density is a measurement of the PSA level divided by estimation of prostate volume determined by transrectal ultrasonography and simply implies that the PSA value is adjusted for prostate size. A PSA density of less than 0.1 generally implies a low risk situation for prostate cancer. Free PSA refers to a molecular form of PSA that is not bound to a circulating protein in the blood called alpha₁ -antichymotrypsin. The free PSA measurement is generally higher in men with benign disease, and a measurement of less than 15% suggests clinically significant or more aggressive disease. PSA velocity refers to the change in PSA over time. The greater the rate of PSA increases over time, the greater the threat of a clinically adverse form of prostate cancer. A PSA change of greater than 2 ng/ml in the year before diagnosis means an increased risk of death from prostate cancer.

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Arthur L. Burnett, MD, MBA, FACS
Patrick C. Walsh Professor of Urology, Cellular and Molecular Medicine
The James Buchanan Brady Urological Institute
The Johns Hopkins Hospital
Baltimore, MD