The Prostate. Part 2
Detecting Prostate Cancer: Prostate-Specific Antigen Assay
If prostate cancer is diagnosed and treated during early stages, patients have a 5-year survival rate of 94%. However, the difficulty lies in the diagnosis. Prostate cancer is usually a silently spreading disease with no symptoms until the cancer has spread beyond the prostate into surrounding organs, bones, or lymph nodes. Fortunately, there is a superb tissue-specific serum marker – the prostate-specific antigen (PSA) – that is highly effective for detecting early prostate cancer. Developed 10 years ago, the prostate-specific antigen assay has revolutionized the diagnosis of prostate cancer. It has also revolutionized patient monitoring. Serum concentrations of PSA are usually less than 4 ng/mL in men with no prostate disease. Concentrations increase by about 0.3 ng/mL per gm of tissue with benign prostatic hyperplasia and by 3 ng/mL/gm with prostate cancer. In absolute values, levels less than 10 are usually considered favorable; levels greater than 50 indicate cancer and suggest that the tumor may already have spread beyond the prostate. A high prostate-specific antigen level may also indicate lymph node involvement. New data also suggest that “normal” prostate-specific antigen levels may be lower in black men, and that new standard ranges should be developed, based not only on age, but on race.
PSA testing has shown that fewer than 2% of men younger than 50 years old have an elevated prostate-specific antigen compared with 10% by age 70. After age 70, the percentage doubles. Similar results have been reported for digital rectal examination (DRE). The percentage of abnormal DRE results increases with age from an average of 9% for men in their 50s to 15% in men 60 to 69 years of age, and 20% for men 70 years old and older.
In addition to screening for cancer, the prostate-specific antigen assay is used to stage the tumor (along with DRE, transrectal ultrasonography, bone scan, computerized tomography [CT] scan, and lymph node surgery). Ultrasound is a safe and easy way to visualize the prostate. It is used to guide the needle during biopsy (for confirming diagnosis), to measure the volume of the prostate for calculating prostate-specific antigen density, and to detect cancer in tissues beyond the prostate. Bone scan can be used to determine whether the cancer has spread to the bone. CT may reveal cancer-positive lymph nodes in the pelvis (although lymph node metastases are usually microscopic and can be detected only by surgical removal of the node). (Garnick MB, Fair WR. Ann Intern Med. 1996;125:118-125. Albertsen PC. JAMA. 1996;275:1857- 1858. Prostate Cancer Education Council.)
The prostate-specific antigen assay is not always reliable. False positives run as high as 65% and false negatives up to about 20%. Today, a number of new diagnostic and staging techniques are under development, including assays that measure percent of free PSA in total prostate-specific antigen. These assays are based on research demonstrating that different forms of prostate-specific antigen – free and complexed – circulate in the bloodstream. Low percentages of free PSA are associated with untreated prostate cancer; high percentages correlate with benign prostatic hyperplasia. The percent-free PSA assays have improved the specificity of total prostate-specific antigen assays without compromising cancer detection. Reducing the rate of false positives avoids the expense (and associated morbidity) of ultrasound and biopsy procedures (an estimated 15 to 40% of biopsies could be avoided). Reducing false negatives improves survival (false-negative rates are generally estimated at 0 to 10%). Almost all the prostate-specific antigen manufacturers – Hybritech (a Beckman subsidiary), Abbott, UroCor, Dianon, and Ciba-Corning – have a free PSA assay, but none is FDA approved. (American Urological Association Annual Meeting in Orlando, FL, 1996.)