Screening Tests

While a PSA (Prostate Specific Antigen) test is not perfect, it remains the gold standard screening tool when it comes to detecting prostate cancer. But it only looks for elevated levels of prostate and not prostate cancer. PSA exists in the blood either free or bound to the proteins alpha-1-antichymotrypsin or alpha-2-macroglobulin. People with prostate cancer have more of the form bound to alpha-1-antichymotrypsin and less of the free form than do healthy men or those with benign diseases of the prostate.

Initial screening for prostate cancer commonly uses the total PSA test, which measures all but the third form of PSA. If the result is slightly elevated, follow-up testing is often performed using another test that measures free PSA. These tests have been criticized by some as being associated with too many false positives and false negatives. It was hoped that the new CPSA test would replace these so that only a single screening test would be needed.

In a study by researchers from Johns Hopkins and the New York University School of Medicine, the CPSA test (1) demonstrated improved specificity over a total PSA assay, reducing the number of false positives and (2) concluded that CPSA could be used as a first-line test for prostate cancer screening.

However, in several studies published this year, the advantage of CPSA over total and free PSA tests was less convincing. In a trial at the University of Texas M.D. Anderson Cancer Center, the CPSA assay was only found to be equivalent to a total PSA test for early detection. In another study of 535 patients conducted by McGill University, the ratio of free-to-total PSA performed better than either CPSA or total PSA alone in prostate cancer detection.

A new urine test can tell prostate cancer from an enlarged prostate but cannot tell whether the cancer is deadly. San Diego-based Gen-Probe is approved in some European countries, but not in the U.S. It detects genetic material—RNA—from prostate cancer gene 3 or PCA3. PCA3 (previously known as the DD3 gene) is found only in the prostate. When prostate cells become cancerous, their PCA3 genes go wild. Prostate cancer cells express 60 to 100 times more PCA3 RNA than normal cells.

The studies showed (1) the PCA3 test is not influenced by the size of the prostate, even in people with BPH, and (2) the test can help men decide whether they need a repeat prostate biopsy. Prostate biopsy involves multiple needle punctures into the walnut-sized prostate gland. PCA3 is among the most prostate-cancer-specific markers ever identified. A recent improvement to the value of the Prostate Specific Antigen Density (PSAD) is doing a PSAD of the transition zone (TZ) of the prostate (PSAD-TZ). PSAD-TZ has been shown to be more accurate than a simple PSAD of the entire prostate gland.

New studies at Johns Hopkins of a blood protein recently identified as early prostate cancer antigen-2 (EPCA-2) may change the way men are screened for prostate cancer. “A blood test based on EPCA-2 may greatly improve our ability to accurately detect prostate cancer early and minimize the number of false positives, therefore lowering the number of unnecessary biopsies,” says Getzenberg. “In addition, this is the first time we have a test that effectively distinguishes between men with cancer confined to the prostate and those whose disease has spread outside of the gland.” Tessera Diagnostics in Seattle has developed the EPCA test (available at Unipath, LLC in Denver, Colorado), and it will soon be offered by pathology laboratories throughout the country, as well as major prostate cancer centers. Pathologists will use the test to assist in the detection of prostate cancer in biopsy tissue samples in ways not currently possible, and will then report their findings to the patient’s urologist.

In the April issue of Urology, researchers reported finding the EPCA-2 blood test far more effective than the traditional PSA. According to Nature, researchers took the first steps towards devising a urine test for detecting prostate cancer (February 2009). A chemical fingerprint called sarcosine can be found in high levels in the urine of men with aggressive cancer of the prostate, thus providing a potential biomarker of the disease. Researchers found that concentrations of sarcosine were high in 79% of samples with metastatic prostate cancer and in 42% of the samples of early-stage cancer.

Stromal protein (caveolin-1), a new marker for advanced prostate cancer and metastasis of the disease, has been identified by US researchers. Prostate tissue from men with localized prostate cancer revealed that the men had significantly decreased levels of a stromal protein called caveolin-1. The researchers also found that the protein was not present in tumor tissue from men with metastatic prostate cancer. Lower levels of caveolin-1 were associated with a high Gleason score. The absence of this stromal protein caveolin-1 is also associated with advanced tumor stage, early recurrence and metastasis of breast cancer.

Men with advanced cancer--those with the highest level of C-reactive protein—died significantly sooner than men with lower levels. C-reactive protein is a sign of inflammation, which doctors increasingly think is associated with cancer progression and cancer resistance to treatment. A recent remedy, Serraflazyme, has shown to reduce inflammation. Serraflazyme is an anti-inflammatory proteolytic enzyme, the enzyme isolated from the micro-organism, serratia E15, naturally present in silk worm intestines. Serraflazyme is a naturally-occurring, physiologic agent with no inhibitory effects on prostaglandins and is devoid of gastrointestinal effects.

Primary blood tests: PSA, PAP, testosterone panel, estradiol, progesterone, LH, prolactin.

Lymphocytes subset panel: CD3, CD4, CD8, CD19, NK, percentage and absolute count, not just percentage. Secondary tests: CGA, CEA, NSE, TGF-b1, IL-6Sr, CA 125.

Urine: HCG